To investigate factors which influence stroke survivors' decision-making about their rehabilitation and the prospect of taking recovery-promoting drugs, to enhance their recovery.Seventeen stroke survivors who had undertaken stroke rehabilitation, and three spouses, participated in focus groups and individual interviews in northern Queensland, Australia. Inductive thematic analysis of the interview data was conducted in accordance with Braun and Clarke's six-phase process.Two specific, pivotal decision points during participants' stroke recovery process were identified: 1) overall, when deciding what rehabilitation they would undertake and hypothetically what recovery-promoting drugs they would take, and 2) on a daily basis, when deciding whether to participate in rehabilitation and take recovery-promoting drugs on any given day. Six themes which described factors influencing their decision-making were: ‘My options for rehabilitation and recovery-promoting drugs’; ‘The costs of rehabilitation and recovery-promoting drugs’; ‘My recovery goals’; ‘What I can deal with today’; ‘The people my rehabilitation and recovery-promoting drugs affect’; and ‘Fitting rehabilitation and recovery-promoting drugs into my life.’ These themes were applicable at either one or both of the identified decision points.Factors that influence stroke survivors' decision-making, overall and on a day-to-day basis, need to be considered to ensure they can make the best decisions for themselves to achieve their full recovery potential. Understanding the conditions under which a stroke survivor would take a recovery-promoting drug will contribute to the development of dosing protocols to which stroke survivors could adhere. Version 12.2.5The primary researcher and interviewer/focus group facilitator (NF) is a pharmacist with experience working in a community-based neurological rehabilitation centre in regional Australia and has training in qualitative research methods. NF worked with an experienced team of three stroke rehabilitation physiotherapists/researchers  and a health professional academic specialising in qualitative research methods (RR). The primary researcher held no prior relationship with participants. It was made clear that NF was a pharmacist seeking to learn more about factors influencing stroke survivors' decision-making about stroke rehabilitation options, with a particular interest in recovery-promoting drugs.33.1The final 20 participants were drawn from 25 potentially eligible participants, one of whom withdrew before interview due to poor health and four who did not respond after the screening process. Of the 20 participants, 17 were stroke survivors and three were spouses of stroke survivors who attended to support and assist with communication. Participant demographics are summarised in 3.2Participants discussed a wide range of reasons why and how they made decisions to participate in rehabilitation and hypothetically, why they would take RPDs. Whilst the decisions each participant made were personal and unique, many similar factors influenced their decision making. Six strong themes were identified from the data. It became apparent that these themes were relevant at two specific decision points in participants' recovery process .Fig. 1FaThe first decision point occurred when participants chose the type of rehabilitation they would undertake, or hypothetically, when they would agree to start taking RPDs. At this point their decision appeared to be influenced by: ‘My options for rehabilitation and RPDs’ and ‘The costs of rehabilitation and RPDs.’ The second decision point occurred on a daily basis, when participants decided whether to actively engage in rehabilitation that day and to what extent, or whether to take a prescribed dose of RPD. This decision point appeared to be influenced by ‘My recovery goals’ and ‘What I can deal with today.’ A further two themes were applicable at both decision points: ‘The people my rehabilitation and RPDs affect’ and ‘Fitting rehabilitation and RPDs into my life.’Decision point 1: Deciding which rehabilitation to do or which RPD to take.‘My options for rehabilitation and RPDs.’“But I think some of the things I've done, have really, really helped me. And there are things that others have really helped them that I don't know about.” .Knowing what options were available clearly influenced decision-making, however this varied widely between participants. Some were aware of the options available to them, while others learned of new, different options as time passed.“I have had no rehab at all from anybody or any organisation [since returning from hospital] because I live in [small rural town].” .Some participants knew of options but believed they were ineligible.Whether excluded due to real or perceived barriers, participants believed that some rehabilitation options were not feasible for them. Some reported they could not organise consistent transport, or waiting lists were too long. Others believed it was too late and they were ineligible when they eventually learned of rehabilitation services.When discussing RPDs, participants said they would be willing to give anything a go, suggesting they would ‘probably have no hesitation’ to take an experimental or ‘miracle’ drug. Some participants had explored options for stem cell treatments and natural therapies, although did not follow through to join trials.‘The costs of rehabilitation and RPDs.’“My gym program was set up by a physio from [community-based rehabilitation service]. He came with me the first time, he set up a program, but if you're on $AU250 a week, you can't afford $AU14 a week to go to a gym, and $AU4 a day to go to a pool.” .Participants discussed the effort, losses and sacrifices associated with rehabilitation and RPDs after stroke. These costs were both financial and non-financial.“At that time [participant's parents] were self-employed, they were fortunate enough to be a little bit more flexible… in the long term, it impacted on their financial income as well. … there was a lot of waiting round for them.” .Personal costs discussed by participants included discomfort experienced; inconvenience and burden of rehabilitation and RPDs for both them and their families; and time that attending rehabilitation would take out of their lives.“I wouldn't have any hesitation if back then the epilepsy drug cost $60 a month. If it controlled my seizures [after the stroke] that would … be sufficient, because I'm getting a result that I want.” .When discussing RPDs, participants spoke of justifying the expense of a medication with the value gained from taking it.Decision point 2: Deciding whether to participate in rehabilitation or take dose of RPD today.‘My recovery goals.’“What drives me is I still need a goal.” .Their personal recovery goals influenced whether a participant would actively engage in their rehabilitation that day. The rehabilitation plan was shaped by their goals, and these goals motivated the participants to persevere.“They actually came out to my shed… looked at everything I had… and what I was trying to do… the next time I showed up for an OT session she pulled out a tin full of nuts and bolts… I had to put the nuts and bolts and washers and all that sort of stuff together. And you know, that all made sense.” .The rehabilitation clinician's goals for the session also influenced participants' decisions to actively engage. When participants understood the clinician's goals, they were more motivated.“One of [my goals] was to get up off the floor… I'd work with the same person for a couple of weeks… but then you'd go in next time, someone different, and they go, ‘we'll do this and we'll do that,’ and then there go[es] all the work you've just built up.” .When participants could not align the clinician's goals for the rehabilitation session with their personal recovery goals, they expressed dissatisfaction with the service, disillusionment with the rehabilitation process and distrust of their clinician's capacity.“I hadn't noticed being drowsy [while on a prescribed medication] but I was just worried about getting drowsy you know, because I wanted my license back and driving again…” .The decision to take RPDs was often influenced by the impact on participants achieving their goals.“Well, I can't put on headphones. Because they require two hands. …. If I had my hand back, I would be able to get on a wig.” .Achieving rehabilitation goals despite experiencing side-effects due to RPDs was considered worthwhile in some instances. A participant used a hypothetical example of a RPD that could cause hair loss but enhanced recovery of hand function during rehabilitation.‘What I can deal with today.’How they felt and what they could deal with that day influenced participants' decisions to engage in rehabilitation or take RPDs. Some participants reported that they would ‘do anything’ or ‘have a crack,’ particularly ‘if it's going to help me.’“I was very committed to my physios at the hospital, and I think some of those more personal relationships, more than anything, kept me there…” .Positive relationships with clinicians, and believing the clinicians were invested in their recovery motivated participants to actively engage in their rehabilitation sessions.“You've got a program… you're working towards something… you feel like you're going in the one direction. Every day you're doing more or better at it, then you get a different person that works with you, and they go, I just want to try this with you…. I'm like, ‘I'm not just here for a guinea pig, for you to try this.’ I understand they want to tweak exercises… but there's tweaking and there's trying a completely different thing and going in a completely different direction, and that's what it felt like a lot.” .Conversely, some participants who worked with different clinicians at each rehabilitation session expressed their dissatisfaction. They did not want to ‘explain [their story] all again’ to a new clinician. If the new clinician suggested something different or deviated from the set rehabilitation plan some participants felt the clinician was experimenting.“You followed everything through because that's what you had to do. You didn't try to get out of it the easy way, whether you got up in the morning and didn't feel like going, you still done it because that's what you had to do.” .The extent to which participants would engage in rehabilitation on any given day differed. Participants' experiences ranged across a spectrum, from not attending rehabilitation at all, to being present but skipping activities, to going through the motions of the exercises without injecting effort or heart. However, it was almost universally acknowledged by participants that ‘no one else is going to do it for you.’“And that stage in the game I was in so much pain I would've taken bloody rabbit pellets if it worked.” .When it came to taking RPDs, some participants said that if it helped them, they would take it no matter the downside. Conversely, some participants said they would only tolerate so much.“It's a bit of a stretch to get up four o'clock in the morning every day [to take a tablet] and within two months I'm just the same.” .Both decision points: Factors which influenced decisions at both decision points.‘The people my rehabilitation and RPDs affect.’Participants often made decisions for and because of others in their life at both decision points. In some cases, participants described making decisions because it was beneficial to another person. Some were motivated because they wanted to recover for those they cared about.“I think you've got to realize that you've got a loving partner….who's with you and going through this. It's just as hard on them…They suffer along with you.” .Family members were often involved in decision making, especially when transport and finances were considerations. When resources like money or vehicles were shared, and the spouse was the main income earner or responsible for transporting the participant, this was important. Additionally, some participants described the impact of their stroke on their partner, feeling that their partner's life had been irrevocably changed.sic) mainly for her. I'd rather do it for her than just for me. She's your loved one… she has to put up [with] a lot.” .“I'd like to get better anyway but my .’” .“I think there's a bit of blind trust, with, with doctor…Doctor says, ‘Oh, this does X Y Z and I will prescribe for you this Other participants said they took their prescribed medications because their ‘doctor said so’.‘Fitting rehabilitation and RPDs into my life.’“I get invited somewhere, well, then, I've got to research it. What's the gutter look like, what's the footpath look like, how can I get in, can I go to the toilet? …Those [rehabilitation] timetable changes would just kill you…Because you're already trying to organise your support worker in the morning… and then transport, and then there's the knock-on effect of rearranging everything too.” .How rehabilitation would fit into the participants' and their family's daily schedule influenced participants' decisions about what rehabilitation to do. Timing and changing of times, energy levels and need for rest, and being able to negotiate the environment around them all came into play.“…There's no limit to what I would pay. … I would use up all my super[annuation]… One of my ultimate dreams is to go back to work…” .Participants discussed how the phase of their life impacted their decision-making. Whether they saw themselves as a student, a worker, a family-maker, or retiree – participants would make decisions about potential rehabilitation and RPDs with this in mind, and were prepared to go to great lengths.“[If] I had to be away … from my children for a significant period of time – it would affect the decision-making because I've got dependents… I would have to think about what I would do with my family if I had to leave them for an extended period of time.” .On having a stroke in their early twenties:…You have this window of opportunity now. If you don't do that, you don't get that chance again.” .Participating in the right amount of rehabilitation for their stage of recovery, especially the early stages of recovery, was important to participants. Where rehabilitation of higher intensity or frequency was available, participants described wanting to take advantage of windows of opportunity, with the understanding that it would increase neuroplasticity, which would lead to a better recovery.“I probably wouldn't like it, but if I knew it was going to prevent something or help something, I'd take it.” .Participants talked about the negatives and positives of taking RPDs, however these factors were of varied importance within and between participants. Participants discussed trade-offs between possible recovery outcomes and perceived drawbacks.“I don't think so…. Because I'm already taking enough medicines.” .4,,The factors that were identified to influence stroke survivors' decision-making about their rehabilitation and the prospect of taking RPDs to improve recovery, and the six themes within which they could be categorised, were not dissimilar to the factors discussed in the broader literature.,,Recognizing the two important decision points along the recovery trajectory provides a new perspective. The focus of previous qualitative stroke recovery studies has been on factors that constitute ideal therapy for stroke survivors, and the facilitators and barriers to their participation in their rehabilitation.,entire stroke rehabilitation process if they are to gain any potential benefits of RPDs. The recovery pathway stroke survivors choose and how they engage with rehabilitation daily requires consideration of factors for both physical and behavioural interventions and RPDs. Committing to RPDs requires commitment to the physical or behavioural intervention, as RPDs do not currently appear to lead to stroke recovery on their own. Therefore, considering factors for RPDs along with physical or behavioural interventions when deciding which stroke recovery process to undertake is more likely to lead to success.Factors influencing stroke survivors' decision-making about rehabilitation and RPDs will be relevant when investigating RPDs in the future. The best available evidence suggests that RPDs must be paired with physical or behavioural interventions to drive activity-dependent biological processes associated with stroke recovery.While the outcome of this study offers new and valuable insights into factors affecting stroke survivors' decision-making regarding their rehabilitation or taking RPDs, several methodological limitations must be discussed to place these findings within perspective. Firstly, as all study participants volunteered to attend, findings may reflect views of those for whom recovery is a priority.Insights gained from this study can aid development of discrete choice experiments investigating stroke survivors' preferences for RPDs as part of a rehabilitation program. To date, such investigations have not been undertaken as RPDs are still being trialed. To illustrate, a discrete choice experiment could be conducted during protocol development for a trial investigating the benefits of taking a candidate RPD in conjunction with task-specific training. Determining the most favourable combination of attributes for the RPD dosing regime and task-specific training sessions, based on participants' preferences, may lend itself to higher rates of participation and adherence to the trial protocol, which in turn may lead to more robust results.Investigating factors which influence stroke survivors' decision-making about rehabilitation and RPDs has highlighted two important decision points. Acknowledging these critical decision points means stroke survivors can be supported in those moments to make the best decisions for themselves to participate in rehabilitation and take RPDs to achieve their full recovery potential. RPDs alone have not been shown to be effective; future investigations into their efficacy must include a physical or behavioural intervention component. To achieve optimal recovery with a combined RPD and rehabilitation intervention, stroke survivors will need to adhere to both components. Poor adherence to any stroke rehabilitation intervention will deliver underwhelming outcomes. The findings highlight the importance of not making assumptions about why stroke survivors' make decisions about their rehabilitation or RPDs, but rather understanding the interplay between factors which influence their decisions. Understanding these factors and exploiting them in the design of person-centred rehabilitation and RPD interventions, will see higher engagement and increased recovery outcomes.NF conceived the research question and design of the interview topic guide. NF and RR analysed the data. NF and RB interpreted the data. All authors were involved in the writing and critical revision of the manuscript. All authors have read and approved the manuscript.No potential conflict of interest was reported by the authors.


Although rotavirus A (RVA) is the primary cause of acute viral gastroenteritis in children and young animals, mechanisms of its replication and pathogenesis remain poorly understood. We previously demonstrated that the neuraminidase-mediated removal of terminal sialic acids (SAs) significantly enhanced RVA-G9P[13] replication, while inhibiting RVA-G5P[7] replication. In this study, we compared the transcriptome responses of porcine ileal enteroids (PIEs) to G5P[7] vs. G9P[13] infections, with emphasis on the genes associated with immune response, cholesterol metabolism, and host cell attachment. The analysis demonstrated that G9P[13] infection led to a robust modulation of gene expression (4093 significantly modulated genes vs. 488 genes modulated by G5P[7]) and a significant modulation of glycosyltransferase-encoding genes. The two strains differentially affected signaling pathways related to immune response, with G9P[13] mostly upregulating and G5P[7] inhibiting them. Both RVAs modulated the expression of genes encoding for cholesterol transporters. G9P[13], but not G5P[7], significantly affected the ceramide synthesis pathway known to affect both cholesterol and glycan metabolism. Thus, our results highlight the unique mechanisms regulating cellular response to infection caused by emerging/re-emerging and historical RVA strains relevant to RVA-receptor interactions, metabolic pathways, and immune signaling pathways that are critical in the design of effective control strategies. Rotaviruses (RVs) are a leading cause, globally, of acute viral gastroenteritis in both children and production animals . The gloSedoreoviridae family, Rotavirus genus, this nonenveloped virus possesses 11 segments of double-stranded RNA (dsRNA) in a triple-layer viral capsid. These 11 segments encode dsRNA for structural proteins  and non-structural proteins (NSP and NSP1-5/6)  (G9P[13] strain) and RVA G5P[7] were used in the study. Intestinal contents were diluted at a 1:10 ratio in sterile minimal essential media . Contents were then centrifuged at 2095× 5 fluorescent foci units/mL) were activated prior to infection using 10 µg/mL trypsin  for 30 min at 37 °C and diluted in complete medium without growth factors (CMGF-) to achieve the desired MOI (1.0). PIEs were incubated with RVAs for 1 h at 37 °C and then washed twice with CMGF- and placed in 96-well plates in triplicate and harvested at 24 hours post-infection. Mock control PIE cells were treated identically, but inoculated with CMGF- with 10 ug/mL trypsin without RVA. Plates were kept at −80 °C until RNA was extracted from homogenized cells using a MagMAX™ Viral/Pathogen Nucleic Acid Isolation Kit .The rotavirus infection protocol was described by Guo et al. . BrieflySus scrofa 11.1 genome release 97  using the Rsubread aligner  vs. G5P[7] replication on the host (PIE) gene expression profile, we used transcriptome analysis. We demonstrated that G9P[13] replication in PIEs resulted in significant modulation of the expression of 4093 genes , with 19F11R . Infection with both RVAs only marginally modulated the expression of gene encoding integrin αvβ3 (data not shown). However, G9P[13] infection of PIEs led to a significant upregulation of tight junction protein JAM-A—F11R , while tynthesis ) after iRIG-1) by G5P[7] ; molecules associated with different functions including immune regulation [“role of double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in interferon induction and antiviral response” and “N-formyl-Met-Leu-Phe (fMLP) signaling in neutrophils”] . Furthery G5P[7] B. This fAdditionally, IPA identified the top significantly affected molecules and G9P[13] infection had a staggering >200 fold-change increase of ANPEP and TMIGD1, suggestive of an increased granulocyte and cell recovery response . Of intep-value—1.944)—while G5P[7] infection was not associated with significant changes in cholesterol-related pathways. Ceramides are important bioactive sphingolipids involved in a variety of cellular processes such as cell growth and differentiation, inflammation, and apoptosis, including the biosynthesis of oligosaccharides and, therefore, gangliosides  resulted in a significant upregulation of only one pathway associated with lipid metabolism—the ceramide pathway , the dominant negative inhibitor of basic helix-loop-helix proteins (ID1) , the groGlobally, we face a prevalence of emerging RVA strains with seemingly increased interspecies transmission potential, such as G9P[13] ,53,54,55In sharp contrast with previous observations suggestive of more efficient G5P[7] vs. G9P[13] replication in vivo and in vitro , ourThe significant modulation of the expression of the genes encoding sialyltransferases and fucosyltrasferases and some attachment factors following G9P[13] infection suggests that this RVA could have evolved a mechanism regulating the availability of cell attachment factors, including unmasking additional receptors that can be covered by glycoconjugates. Importantly, sialyltransferases are enzymes responsible for SA transfer to nascent carbohydrates and they can regulate the availability of RVA attachment sites. Infection with the sialidase-dependent RVA strain, G9P[13], significantly modulated (mostly downregulated) the expression of the genes encoding sialyltransferases of the four major families, ST3Gal, ST6Gal, ST8Sia, and ST6GalNAc , which mABO with both cholesterol  induced a significant upregulation of the IL-6 and IL-8 signaling pathways that have been previously shown to be involved in the pathogenesis of acute RVA-associated gastroenteritis . HoweverApart from the potential link to T1 diabetes, RVAs have not been demonstrated to have long-term health effects, to the best of our knowledge . HoweverTaken together, this study demonstrated strain/genotype-specific modulation of the host cellular response to RVA infection, further emphasizing the unique interactions between SAs and other host factors and G9P[13] and G5P[7]. Additionally, our results suggest that long-term circulation and adaptation to swine might have increased the within-host viral fitness of G5P[7] RVA, resulting in higher replication rates and a reduced transcriptome/immune response. In contrast, G9P[13] replication was associated with a robust modulation of the host transcriptome and a significant downregulation of sialyltransferase expression. Importantly, the latter can lead to decreased sialylation and the unmasking of additional attachment factors, including gangliosides. We plan to further investigate these results, using reverse genetics and CRISPR-Cas9 gene editing to mechanistically analyze G9P[13]-specific interactions with SAs to increase its replication, and to determine how to manipulate this mechanism to reduce its growing global prevalence.


Using the same observers, Experiment 2 examined the effect of the identical surround-ring parameters on target patch matching luminance in the presence of a dark (0.0 cd/m2) and a bright (96 cd/m2) remote background. By differencing the results of Experiment 1 (the isolated effect of the surround-ring) from those of Experiment 2 (the combined effect of the surround-ring with the dark and bright remote background) we further isolated the effect of the remote background. The results reveal that surround-rings and remote backgrounds produce brightness contrast effects in the target patch that are of the same or opposite polarity depending on the luminance polarity of these regions relative to target patch luminance. The strength of brightness contrast from the surround-ring varied with surround-ring luminance and width. Brightness contrast (darkening) in the target from the bright remote background was relatively constant in magnitude across all surround-ring luminances and increased in magnitude with decreasing surround-ring width. Brightness contrast (brightening) from the isolated dark remote background also increased in magnitude with decreasing surround-ring width: however, despite some regional flattening of the functions due to the fixed luminance of the dark remote background, induction magnitude was much reduced in the presence of a surround-ring of greater luminance than the target patch indicating a non-linear interaction between the dark remote background and surround-ring luminance.The brightness (perceived intensity) of a region of visual space depends on its luminance and on the luminance of nearby regions. This phenomenon is called brightness induction and includes both brightness contrast and assimilation. Historically, and on a purely descriptive level, brightness contrast refers to a directional shift in target brightness away from the brightness of an adjacent region while assimilation refers to a brightness shift toward that of an adjacent region. In order to understand mechanisms, it is important to differentiate the descriptive terms contrast and assimilation from the optical and/or neural processes, often similarly named, which cause the effects. Experiment 1 isolated the effect on target patch (64 cd/m This phenomenon is called brightness induction and includes both brightness contrast and brightness assimilation effects. Historically, and on a purely descriptive (as opposed to mechanistic) level, brightness contrast induction is said to occur when the brightness of a target region shifts  Helson, . Helson  Helson,  studied  Helson,  found th Helson, .contrast and assimilation that merely specify the direction of a brightness induction effect on a region in relation to its adjacent surround, and the actual optical or neural mechanisms that produce the directional shifts. For example, optical  blurring has been shown to contribute to brightness assimilation under some high-frequency conditions  bars remained white (125 cd/m2) or black (3.0 cd/m2). Under these conditions the influence of the collinear and flanking bars was found to be purely in the direction of contrast as predicted by the ODOG model. The effect was dominated by contrast from the collinear bars (which results in White’s effect); however, the influence of the flanking bars was also in the contrast direction. These findings ruled out mechanistic explanations of the White effect in terms of brightness assimilation from the flanking bars  of a target  and the width of the adjacent surround . They concluded that under their conditions the remote contrast effect (the effect of the remote background on the 11’ radius target patch) was less than the adjacent contrast effect (the effect of the remote background on the adjacent surround brightness) and that the remote contrast effect decreased as a function of distance between the target edge and the remote background luminance edge . Reid and Shapley  in a constant 50 cd/m2 adjacent surround-ring (2.0°), on remote backgrounds of 10, 40, 60, 90 cd/m2. The matching disk was the same size as the target (reference) disk and was presented on the remote background (no surround-ring). These investigators concluded that while same polarity edge signals produced same polarity contrast effects on the target disk, opposite polarity edge signals produced contrast signals that were opposing. They argued that the balance between these opposing signals depended on the relative strength of the induction signals from these edges such that a high-contrast remote induction signal can completely overwhelm the opposing signal from an adjacent surround-ring. Although they referred to this effect as an assimilation effect, in terms of mechanism it is actually the “contrast at a distance” effect (what we refer to as remote contrast in this article) coined by Reid and Shapley (2) and that irrespective of the polarity between local and remote inducers, their matching data were best described by a model in which gain varied with background luminance.Vladusich et al.  also stu Shapley . Similar Shapley , Vladusi Shapley  found th2) than the adjacent surround-ring luminance (1.48–4.47 cd/m2); and therefore, the edge between the remote background and adjacent surround-ring was labeled a decrement. Similarly, the adjacent surround-ring luminance (1.48–4.47 cd/m2) was higher than the target-disk luminance (1.0 cd/m2) and also labeled a decrement. Note that we follow this naming convention in the present article, however, it is important to be aware that the starting direction is arbitrary. For example, in Vladusich et al.  on a remote background that had the same mean luminance as the target (64 cd/m2). Experiment 2 examined, in the same four observers, the effect of these identical conditions on target patch matching luminance in the presence of both a dark (0.0 cd/m2) and a bright (96 cd/m2) remote background. Finally, we differenced the results of Experiment 1 (the isolated effect of the adjacent surround-ring) from those of Experiment 2 (the combined effect of the adjacent surround-ring with the dark and bright remote backgrounds) to obtain a view of the data that, to at least a first approximation, further isolated the effect of the remote background on target brightness.The current study resolves some of the above differences regarding the induction effects of adjacent and remote backgrounds on target patches not through modeling (or curve fitting) their combined effects, but by experimentally isolating the effects of both surround-ring luminance and remote background luminance on target patch matching luminance over a wide range of parameters. This approach was inspired by the work of Reid and Shapley , discussOur results support those of Vladusich et al.  as opposIn addition, we argue based on the literature reviewed above that induction effects are unlikely to be based purely on the “filling-in” of edge signals as implied by edge-integration models. As discussed by Kingdom , all edgTwo male (ages 30 and 62) and two female (ages 21 and 62) with normal or corrected-to-normal vision participated in the experiment. Each participant provided informed consent and the experimental protocol was approved by the NDSU Institutional Review Board.via look-up tables created based on photometric calibration . The 105 cm × 59 cm display was viewed at 110 cm and subtended 50° × 29° of visual angle. The sequencing and timing of image presentation and the collection of observer responses was controlled using Presentation . The target patch, adjacent surround-ring, and remote background of the stimuli occupied the upper two-thirds of the display. The radius of the circular target patch was 0.5° in all conditions. In Experiment 1 the adjacent surround-ring widths were 0.1°, 0.3°, 0.5°, 1.0°, 2.5° or 24.5° such that the target patch plus adjacent surround-ring radii measured 0.6°, 0.8°, 1.0°, 1.5°, 3.0°, and 25°. Target patch luminance was held constant at 64 cd/m2. For each of the six adjacent surround-ring sizes, the surround-ring luminance was varied from 32 to 96 cd/m2  on a background 64 cd/m2. 2 remote background, respectively. In panels A–C adjacent surround-ring luminance is 32 cd/m2, in panels D and E adjacent surround-ring luminance is 96 cd/m2. Note that in panel F surround-ring luminance is 64 cd/m2. For all surround-ring sizes this surround-ring luminance results in the stimulus reducing to a homogeneous field since target patch, adjacent surround-ring, and remote background are all 64 cd/m2. Finally, panels G and H illustrate the expanded adjacent surround-ring condition (24.5° width). This expanded surround-ring covered the full extent of the stimulus display (50° × 29°) resulting in a target patch (0.5° radius) in a large adjacent surround. As in the other conditions, this large adjacent surround varied over the full range of adjacent surround-ring luminance. Panels G and H illustrate this stimulus when adjacent surround-ring luminance was at the extremes of this range .Stimuli were presented on a second-generation high-dynamic-range (HDR) monitor  comprised of a 47”, 60 Hz LCD display with 1,920 × 1,080 pixel front-panel resolution, and a backlight matrix consisting of a hexagonal array of 2,202 high intensity LEDs. Stimuli were generated using MATLAB routines and presented as pseudo-grayscale images possessing 1,000 linear intensity steps using the bit-stealing method of  and the large adjacent surround was not retested. Note that 0.0 cd/m2 refers to a photometric reading of less than 0.005 cd/m2 on the high dynamic range display. 2, 64 cd/m2, and 89.5 cd/m2) on each of the two remote backgrounds (0.0 and 96 cd/m2). The upper pair of panels  show identical target patch  and adjacent surround-ring  stimuli on the 0.0 cd/m2 and 96 cd/m2 remote backgrounds, respectively. Likewise, the bottom pair of panels  depict identical target patch  and adjacent surround-ring  stimuli on the same two remote backgrounds (0.0 and 96 cd/m2). Note that in the middle pair of panels  adjacent surround-ring luminance is equal to the target patch luminance (64 cd/m2) resulting in a stimulus discontinuity that reduces to a simple target patch in a large contiguous surround. These stimuli appear similar to the large surround-ring stimuli from Experiment 1  that was vertically centered in a homogeneous field (64 cd/m2) which occupied the lower third of the display. The checkerboard background measured 2.0° H × 2.0° W and the individual checks measured 0.25° × 0.25°.In both Experiments 1 and 2 square matching patches (1° × 1°) were presented on a checkerboard background  and on the 0.0 cd/m2 and 96 cd/m2 remote backgrounds (Experiment 2). Observers were instructed to adjust the luminance of the matching patch such that its perceived intensity (brightness) matched that of the target patch. Note that because illumination is unambiguously homogeneous in these displays  instructions to match perceived intensity (brightness) produce the same matching luminances as instructions to match perceived reflectance (lightness) . The green stars are the results for the expanded adjacent surround-ring condition in which the adjacent surround-ring filled the entire background of the stimulus. The horizontal dashed line represents a veridical luminance match to the target patch (64 cd/m2) and the vertical dashed line indicates the location where adjacent surround-ring luminance equals target patch luminance. The stimulus icons appearing at the top and bottom of 2) and variable adjacent-surround rings, on the dark (see stimulus 2 background (red symbols) and for the full field variable adjacent-surrounds (green stars) are replotted in 2, vertical dashed line) the stimulus icons for the dark (top left) and bright (bottom left) remote backgrounds are labeled Inc-Inc and Dec-Inc, respectively, following the naming convention of Rudd and Zemach (2) or bright (96 cd/m2) remote background and the variable luminance (32.0–57.6 cd/m2) adjacent surround-ring. On the dark remote background this transition is an increment (Inc) and on the bright remote background it is a decrement (Dec). The second term describes the luminance transition between the variable (32.0–57.6 cd/m2) adjacent surround-ring and the target patch (64 cd/m2). These values are the same irrespective of the dark or bright remote background and the second term is an Inc for both. When adjacent surround-ring luminance is greater than target patch luminance (64 cd/m2), the stimulus icons on the dark (top right) and bright (bottom right) remote backgrounds are labeled Inc-Dec and Dec-Dec, respectively. The middle icons depict the stimulus on the dark (upper) and bright (lower) remote background when adjacent surround-ring luminance is the same as target luminance (64 cd/m2). At this location the stimulus reduces to a target patch of larger size  on the dark or bright remote background . Since the remote background of 64 cd/m2 is not expected to induce a brightness change in a target patch of the same luminance, the green and red matching functions represent the isolated effect of adjacent surround-ring luminance (32–96 cd/m2) on target patch matching luminance at each adjacent surround-ring size. The stimulus icons at the top of 2 remote background (see stimulus 2) and the adjacent surround-rings when surround-ring luminance is below 64 cd/m2. The icons on the right side (top and bottom) depict the luminance relationship between the target patch (64 cd/m2) and the adjacent surround rings when surround ring luminance is above 64 cd/m2. The middle icons depict the stimulus when the adjacent surround-rings are the same luminance as the target patch (64 cd/m2). For all adjacent surround-ring sizes the stimulus at this point becomes a 64 cd/m2 homogeneous field . Matching luminance declines steadily as adjacent surround-ring luminance increases, passes close to veridical matching when surround-ring luminance equals the luminance of the target , and continues to decline reaching the point of maximum darkness induction (lowest target patch matching luminance) when adjacent surround-ring luminance is highest (96 cd/m2). Note that the matching function is asymmetric in that adjacent surround-ring luminances that are less than target patch luminance (64 cd/m2) have less of an induction effect on the target (brightening) than adjacent surround-rings that are greater in luminance than the target patch (darkening). This asymmetry is also seen for the smaller width adjacent surround-rings on the 64 cd/m2 background  the target patch, adjacent surround-ring, and remote background are all equal in luminance (64 cd/m2) resulting in the reduction of the stimulus to a homogeneous field for all adjacent surround-ring sizes .In addition, as expected, the overall magnitude of induction shows an orderly decline with decreasing adjacent surround-ring size. Again, at an adjacent surround-ring luminance of 64 cd/mng sizes . In acco2) remote background (see stimulus 2 remote background (red symbols), represents the brightening effect of the dark (0.0 cd/m2) remote background on the matching functions. The magnitude of this effect of the remote background depends on both adjacent surround-ring luminance and width. Target patch matching luminance is greatest on the dark (0.0 cd/m2) remote background when adjacent surround-ring luminance is less than target patch luminance (64 cd/m2). In this region (Inc-Inc), the remote background (0.0 cd/m2) and the adjacent surround-ring (34–58 cd/m2) are both darker than the target patch (64 cd/m2). Comparing these functions with those on the 64 cd/m2 background (red symbols) indicates that the induction effect on the target patch from the remote background and the adjacent surround-ring are both in the direction of contrast (brightening). The overall upward shift is greatest when the luminance of the adjacent surround-ring is lowest and declines as adjacent surround-ring luminance increases.The filled (black) symbols  depict t2 remote background (red symbols) because the dark remote background has more of an induction effect on the target patches with the smaller adjacent surround-ring widths.Second, brightening from the remote background is moderated by adjacent surround-ring width; induction (brightening) is greatest for the target patches with the smallest adjacent surround-ring widths (black circles and squares) and least for the target patches with the largest adjacent surround-ring width (black inverted triangles). Note that this order is reversed from what is observed on the 64 cd/m2 reverses temporarily at an adjacent surround-ring luminance of 64 cd/m2. This reversal is explained by the stimulus discontinuity at this location mentioned previously. When adjacent surround-ring luminance and target patch luminance are both 64 cd/m2 they are not distinguishable and the stimulus reduces to a target patch of larger size, equivalent to that of the target patch plus the adjacent surround-ring, in a dark background. Since the stimuli now correspond to the classic simultaneous contrast configuration, in accord with this literature  the induction effect (brightening) from the dark (0.0 cd/m2) remote background is strongly counteracted by the induction effect (darkening) due to the increasing luminance of the adjacent surround-ring. As shown by Heinemann  have been removed. Note that for all but the smallest width adjacent surround-ring (black circles) the functions on the 0.0 cd/m2 remote background (black symbols) eventually drop to target matching luminances below veridical and come close to those on the 64 cd/m2 (red symbols) remote background (2 remote background (black inverted triangles) reaches the point of maximum darkness induction in this study (green stars) at an adjacent surround-ring luminance of 96 cd/m2  for all points above the horizontal dashed line . Only the mean target patch matching luminance for the target patch with the narrowest width adjacent surround-ring (black circles), however, remains above veridical at the highest surround-ring luminance (96 cd/m2). This makes sense since, as previously mentioned, the remote background has greater influence (and the adjacent surround-ring less influence) on target patches with narrower surrounds. In this Inc-Dec region the balance between the remote background and the adjacent surround-ring appears to favor the adjacent surround.Again, the counteracting darkness induction from the adjacent surround-ring is greatest in overall magnitude for the target patches with adjacent surround-rings of the largest width (black inverted-triangles) and least for target patches with adjacent surround-rings of the smallest widths (black circles). This can be clearly seen in ckground . Indeed,96 cd/m2 . Recall 96 cd/m2  found th2) remote background (see stimulus 2 background (red symbols) represents the remote induction (darkening) effect of the bright (96 cd/m2) remote background on the matching functions. The magnitude of the induction (darkening) effect from the remote background again depends on both adjacent surround-ring luminance and width. Darkening from the bright (96 cd/m2) remote background is least when adjacent surround-ring luminance is less than target patch luminance (64 cd/m2). This makes sense because in this stimulus region (Dec-Inc) the inducing influence of the bright remote background (darkening) and the dark adjacent surround-ring (brightening) are in opposition. Here, however, the magnitude and rate of decline is much less than occurred for the opposing stimulus condition on the dark remote background .The open (white) symbols  and 5 de2) is brighter than the adjacent surround-ring (Dec-Inc), darkness induction from the 96 cd/m2 remote background is greatest for the target patches with the smallest adjacent surround-ring width (open circles) and least for the target patches with the largest adjacent surround-ring width (open inverted triangles). Note that these data are again consistent with the findings of Vladusich et al.  is apparent for all points below the horizontal dashed line . Here only the mean target patch matching luminance for the target patch with the largest adjacent surround-ring width (open inverted triangles) remains above veridical matching. This makes sense since induction from the remote background is least for the target patches with the largest adjacent surround-ring widths. Note that in this Dec-Inc region (as opposed to the Inc-Dec region discussed earlier) the balance between the remote background and the adjacent surround favors the remote background.Second, the magnitude of the induction (darkening) from the bright remote background also depends on adjacent surround-ring width. When the remote background . This accelerated decline is again explained by the stimulus discontinuity at this location. When adjacent surround-ring luminance and target patch luminance are both 64 cd/m2 they are not distinguishable and the stimulus reduces to a simple simultaneous contrast stimulus . The removal of the counteracting inducing effect (brightening) from the adjacent surround-ring luminance below the target luminance (64 cd/m2), results in the appearance of an accelerated decline (darkening) in the target matching luminance due to the bright background. This decline is predictably steepest for the target patches with the largest contiguous surround-rings (open inverted triangles) as the larger surround-rings in the Dec-Inc region exerted more counteracting brightness induction on the target. Since the stimuli now correspond to classic simultaneous contrast stimuli, again in accord with this literature  its effect on the target patch is in the same direction (darkening) as the influence of the remote background. The initial apparent upward inflexion for all adjacent surround-ring sizes is consistent with a recovery from the stimulus discontinuity at 64 cd/m2. Note that the overall magnitude of the darkening from both the remote background and adjacent surround-ring in this region (Dec-Dec) is somewhat less than the magnitude of the combined brightening effect in the Inc-Inc condition (black symbols where surround-ring luminance is below 64 cd/m2). As expected, however, the remote background again has the strongest influence on the target patches with the narrower adjacent surround-ring widths. Interestingly, as adjacent surround-ring luminance increases in this region, the different adjacent surround-ring size functions appear to compress toward the point of maximum darkness induction in this study. All of the adjacent surround-ring target patch matching functions on the 96 cd/m2 remote background (white symbols) predictably converge at an adjacent surround-ring luminance of 96 c/m2 since at this point the stimuli all reduce to a 0.5° radius target patch in a full-field 96 cd/m2 surround. The functions also overlap at this location with the full field (50°) surround-ring condition (green stars) since this stimulus is also identical at this point and represents the point of greatest darkness induction  and bright remote (96 cd/m2) backgrounds in greater isolation from the induction due to the isolated adjacent surround-ring luminance (red symbols in 2. This is approximately the case for the difference between the target patch matching functions on the 64 cd/m2 and 96 cd/m2 remote backgrounds (white symbols). The difference functions are all below zero (negative) and appear relatively flat across both the Dec-Inc stimulus region (2 remote background and the 64 cd/m2 remote background (black symbols) are all above zero (positive), however, although some flattening of the functions occurs within the Inc-Inc (2 remote background (black symbols) and darkness induction from the 96 cd/m2 remote background (white symbols) is greatest for target patches with the smallest width adjacent surround-rings and declines in an orderly fashion as adjacent surround-ring width increases.The difference functions also add more clarity to the observation that the influence of the remote background on target patch matching depends in an orderly fashion on the surround-ring width. Brightness induction from the 0.0 cd/m2) on a remote background (64 cd/m2) that had the same mean luminance as the target patch (64 cd/m2). In other words, Experiment 1 was a classic simultaneous brightness contrast study  is relatively constant in magnitude across all adjacent surround-ring luminances and increases in magnitude with decreasing surround-ring width. Induction (brightening) from the isolated dark remote background (0.0 cd/m2) also increased in magnitude with decreasing adjacent surround-ring width. Rather than the dark remote background exerting a constant induction effect (brightening) across all adjacent surround-ring luminances, however, the induction effect from the isolated dark remote background was much reduced in the presence of an adjacent surround-ring of greater luminance than the target patch (Inc-Dec condition) indicating a non-linear interaction between the dark remote background and adjacent surround-ring luminance not observed for the bright remote background.The results of the current study resolve differences in the literature regarding the mechanisms responsible for brightness induction in a target patch from adjacent and remote backgrounds by experimentally isolating the effects of both adjacent surround-ring luminance and width, and remote background luminance on target patch matching luminance over a wide range of parameters. To accomplish this, we examined the effect of both adjacent surround-ring width and luminance in the presence of three remote background luminances. Specifically, Experiment 1 psychophysically isolated in four observers the effect on target patch matching luminance of six adjacent surround-ring widths 0.1°–24.5°) varied over 11 adjacent surround ring luminances  and decreased the target disk matching luminance at high adjacent surround-ring luminance between 5 and 15 cd/m2 (which he described as contrast). In other words, Rudd . Additional support for this interpretation is provided by the finding that we see no evidence of an inflection (brightening) in this region in our 64 cd/m2 remote background condition for any contiguous surround-ring size  North Dakota State University. The patients/participants provided their written informed consent to participate in this study.All authors contributed to the article and approved the submitted version.


This Schiff base shows promise as a ligand for the colorimetric analysis of uranium in water.2-methylene)amino)-3′,6′-bis(ethylamino)-2′,7′-dimethyl-spiro-3-one was synthesized using Rhodamine 6G hydrazide (prepared using literature methods) and commercially available 2,7-dihydroxynaphthalene-1-carbaldehyde via imine condensation. Structural characterization was performed using FT-IR,  StructuIndustrially, Schiff bases have been used as catalysts, dyes, or stabilizers . These cPROM1), a Schiff base synthesized from Rhodamine 6G hydrazide and 2,7-dihydroxynaphthalene-1-carbaldehyde. A related Schiff base was previously reported and shown to have high uranium binding affinity -3-one . When mixed with aqueous solutions of uranyl nitrate, a color change from yellow to pink was observed , 80% hydrazine from TCI (VWR), and uranyl nitrate hexahydrate from Fisher Scientific . Solvents were reagent/ ACS-grade and were purchased from VWR, Radnor, PA, USA. Rhodamine 6G hydrazide was synthesized as described previously in the literature .d6 solution with reference to residual solvent signals . X-ray diffraction data were collected on a Bruker APEX 2 CCD platform diffractometer [Mo Kα (λ = 0.71073 Å)].The IR spectrum was recorded on a Perkin Elmer Spectrum 100 FT-IR, UV-Vis spectra were recorded on a Shimadzu UV-2600i, mass spectrometry was run via direct infusion in pos ESI on an Agilent 6530 QToF HRMS, NMR spectra were collected on a Bruker AXR 500 MHz spectrometer in dimethylsulfoxide-3.2.1H and 13C NMR, and HRMS. HRMS m/z calcd. for C37H34N4O4: 598.26. Found [M + H]+: 599.2641. 1H-NMR (DMSO-d6): 9.57 , 8.00 , 7.73 , 7.70–7.63 , 7.13–7.11 , 6.95 , 6.82 , 6.40 , 6.27 , 3.46 , 3.16 , 2.54 (DMSO), 2.10 , 1.87 , 1.22 , 1.09 . 13C-NMR (DMSO-d6): 163.5 , 158.5 (quat Ar), 157.4 (quat Ar), 151.4 (quat Ar), 151.2 (quat Ar), 148.1 (quat Ar), 147.2 (imine CH), 134.1 (Ar CH), 133.7 (quat Ar), 133.1 (Ar CH), 130.8 (Ar CH), 129.0 (quat Ar), 128.6 (Ar CH), 127.0 (Ar CH), 124.0 (Ar CH), 123.1 (Ar CH), 122.2 (quat Ar), 118.7 (quat Ar), 118.1 (CH3CN), 115.6 (Ar CH), 115.2 (Ar CH), 107.0 (quat Ar), 103.9 (quat Ar), 102.7 (Ar CH), 95.7 (Ar CH), 65.6 (quat C), 56.1 (EtOH), 39.5 , 37.5 (CH2), 18.6 (EtOH), 17.0 (CH3), 14.1 (CH3), 1.22 (CH3CN). FT-IR : 3440.96 (νNH), 3300.00 (νOH), 2964.17 (νCH), 2866.53 (νCH), 1694.78 (νCO), 1617.61 (νCH), 1564.92, 1515.18, 1465.34, 1449.02, 1420.64, 1379.85, 1348.29, 1321.63, 1270.01, 1217.86, 1198.74, 1159.27, 1138.86, 1086.14, 1035.71, 1013.46, 964.98, 923.35, 896.72, 876.22, 859.07, 841.39, 830.84, 811.81, 791.70.To Rhodamine 6G hydrazide , ethanol (15 mL) and acetic acid (5–6 drops) were added. The mixture was stirred to dissolve, and then 2,7-dihydroxynaphthalene-1-carbaldehyde  was added. The resulting solution was stirred for 24 h under reflux at 72 °C. The yellow solid product was separated via hot vacuum filtration . A portion of the product was redissolved in warm acetonitrile, layered with ethanol, and recrystallized via slow evaporation at 5 °C. The yellow crystalline product was used directly for X-ray, 3.3.F2 by SHELXL-2018/3 -3-one (Check CifSupplemental MaterialsCIFMol Document3D Structure Mol


Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using AR ultrasound (AR US) compared with standard US (sUS).Forty-four medical students  who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality. The experimental setup aimed to simulate biopsies of superficial soft tissue lesions, such as for example breast masses in clinical practice, by use of a turkey breast containing olives. Time to puncture(s) and success (yes/no) of the biopsies was documented. All participants completed questionnaires about their coordinative skills and their experience during the training.p = 0.16), nor were there any gender-related differences (p = 0.22 and p = 0.50). AR US was considered by 79.5% of the operators to be the more enjoyable means of learning and performing US-guided biopsies. Further, a more favorable learning curve was achieved using AR US.Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6–60] and 14.5 s [5–41], Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS.Performance of standard and augmented reality US-guided biopsies was comparable• A more favorable learning curve was achieved using augmented reality US.• Augmented reality US was the preferred technique and was considered more enjoyable•  Within the last few years, virtual reality and augmented reality (AR) have been increasingly used in the fields of entertainment and gaming. More recently, they have also been implemented in the field of medicine, particularly for training –4 but alFor example, superimposing a computed tomography (CT) image over anatomical structures enables the operator to visualize deeper structures that would otherwise not be visible on just the surface. This, in combination with planned navigation, has been used to guide injections or biopsies –9, 16–19In this study, we assessed AR US, which has the following capabilities: Images seen through a HMD can by using a voice command either be set steady, to follow the eyes, or be positioned at a certain location, for example below an ultrasound (US) probe. Furthermore, use of tracking objectives by implementing a quick response (QR) code at the US probe can enable the image to follow the tracked US probe. The US image can thus be displayed directly below the US probe in the exact real time anatomical position (in situ image). In a previous phantom study, the performance of inexperienced operators was found to be superior when they used an AR in situ technique . TherefoThe institutional review board approved this prospective, randomized study, and the participants gave their consent to participation.The study cohort comprised 44 medical students  who had no experience in performing biopsies but had completed a standard US course (16 lessons).n = 15) to simulate breast tissue lesions. The phantoms were vacuum packed in transparent, thick plastic wrap  filled with olives n = 5 to simuThe sUS system used was a GE Logiq S7 expert  with a matrix linear probe ML 6-15)  with a linear probe (SL 18-5) and custom-developed software that transmitted the US image to an industry-grade head-mounted AR display (Microsoft Hololens). Furthermore, a QR code that tracked the probe to any position within the room was attached to the US probe Fig. . Two imaThe location of the image to be displayed below the US probe at the exact anatomical position was calculated using the world coordinate system of the head-mounted device and adjusted for a relative offset generated by the US probe head, marked with the QR code. The geometrical properties of the US probe head are exactly known and, together with the applied QR tracking code, an initial calibration to anchor the in situ image correctly in space, as already reported in our previously performed phantom study .This in situ image was relatively small, showing the actual dimensions without magnification (1:1); however, it supports the direct eye-hand coordination for the interventional steps by avoiding size and spatial abstraction Fig. . When thBefore the experiments, students were instructed during 15 min in a standardized fashion regarding the usage of the probe, locating and targeting the lesion, as well as performing the biopsy.Each participant was required to puncture the turkey breast containing the olive-simulated lesions with a 14G disposable core biopsy needle (Bard Magnum) used in concert with a Bard Magnum Biopsy instrument. The students were asked to perform the procedure three times using AR in situ US and three times using sUS. The initial modality was selected randomly, but balanced, 22 participants starting with AR in situ US and 22 with sUS.AR in situ US and sUS were performed in two different rooms with two different supervisors. For sUS, the supervisor was a radiologist who was specialized in imaging of women, whereas for AR US the supervisor was a gynecologist who was specialized in female breast biopsies. Both supervisors had more than 20 years of experience with US-guided biopsies. US settings  were prepared by supervisors, before start of the operator’s task.Primary endpoints were the speed and the accuracy with which the target was punctured. The times taken to identify a target(s) and to puncture that target(s) were measured. In addition, whether the biopsy was successful (more than > 25% of the core biopsy needle filled with olive pulp) or unsuccessful (no or < 25% olive pulp in the core biopsy) was documented.Secondary endpoints were educational experience, relationship to manual coordination in other activities, and ergonomics efficiency. To enable assessment of the secondary endpoints, all participants filled out a questionnaire concerning their coordinative skills, before the interventions. This questionnaire included items such as history of sport activities with hand-eye coordination (such as tennis), playing an instrument, video gaming, and making a self-assessment of their coordinative skills (ranging from 0 to 5). Having a gaming history was defined as regularly playing video games at least once a month.The students also filled out a second questionnaire after the interventions to report which modality they preferred (AR US vs. sUS), which provided a more enjoyable learning experience, and which image they preferred when using the AR US, and which modality was more ergonomically efficient.Study data were collected and managed using REDCap electronic data capture tools hosted at Balgrist University Hospital .Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 27. Descriptive statistics were used to express career aspiration by gender, self-assessment of manual skills, history of playing video games, significant coordinative skills, and number of missed hits using sUS and AR US. Further descriptive statistics were used to assess which of the two techniques was preferred, easier to learn with, and fun to learn with.p-value < 0.05 was considered to denote statistical significance.Medians and ranges were used to report non-parametric data, such as time taken to puncture the targets. Wilcoxon matched-pairs signed rank tests were applied to test for any significant difference between the two US techniques. A The AR US technique was considered more enjoyable to learn with by 79.5% of the participants and 61% indicating that they found the AR technique to be more ergonomically efficient. The AR US technique was preferred by 59% of the participants. In contrast, only 36% preferred the sUS technique and 5% were undecided.p = 0.57 and median [range] to puncture: 17.0 s [6–60] and 14.5 s [5–41], p = 0.16, Table The overall times taken to identify and puncture a target with AR US and sUS did not differ significantly  and their frequency did not differ significantly between the two US techniques (p = 0.71).There were also no significant differences in achievement when the two techniques were compared by gender   Fig. .Fig. 5CA need for visual aids such as lenses or glasses had no detectable influence on outcomes when using the AR technique Fig. .Fig. 6CUse of AR technology is increasing in several fields, including medicine. Early adaptations include image-guided infiltrations , 16, 26,We failed to confirm that our initial hypothesis, which was that inexperienced operators would perform biopsies of soft tissue lesions faster when using AR US than when using sUS, as demonstrated in a previously reported study . PossiblSecond, in this study, the HMD application displayed two US images, one below the US probe at the exact anatomical location (in situ image), and a second image being the same but magnified and visible only when the head was lifted. The in situ image appeared rather small, as its actual dimensions were being viewed. The magnified US image, which was displayed when the head was lifted, was approximately the same size as on a sUS monitor and this magnified image followed the operator’s eyes. Many of the participants were probably initially overwhelmed by the two images, as indicated by the fact that they tended to look up and down repeatedly, presumably deciding which image they preferred for performing the biopsy. With the benefit of hindsight, we should have trained the participants in the AR US technique for better comparability. We tried to compensate for this issue by performing stratified analysis.Third, in the study cited above , the opeOther limitations of the present study were that the supervisors did not change the modality and may have influenced the operators. Additionally, the turkey breast phantoms were not identical in that the olives were inserted randomly. Thus, the ease of obtaining a biopsy may have varied between the prepared phantoms. Further, some air artifacts might have influenced the operators as for 44 operators only four turkey breast were prepared. However, as more than 15 olives were inserted in each turkey breast we think, that the artifacts were of minor relevance. However, given that we used four different breast phantoms, the differences were hopefully distributed approximately equally. Of note, not all four breast phantoms were punctured with both modalities: they were punctured by all operators, but each with only one modality. Retrospectively, it would have been preferable to exchange both the supervisors and breast phantoms between the two modalities. Also, the fact that we had two different US apparatus could have influenced our results. However, we believe that this is negligible, considering that the lesions were easily visible with both US apparatus, and similar US probes were used.Even with all these limitations having deleterious effects on the AR US data, the participants did not generally perform the US-guided biopsies significantly more slowly and the learning curve was better for AR US than for sUS.Detailed analysis of gender distribution showed a tendency for women to perform the biopsies more slowly than their male colleagues when using the AR US technique; however, this difference was not statistically significant. This trend may have been related to the fact that male operators were more comfortable with the AR US technique and some of them had previously worn HMDs, probably associated with gaming histories. Although former studies have found a possible association between experience with gaming and superior performance of laparoscopic surgery , we did Interestingly, although puncturing with AR US was performed more slowly, most participants preferred the AR US technique and reported that it provided a better learning experience. The latter observation is concordant with several reports describing the advantages of 3D teaching and learning by AR use and is of utmost importance , 28, 29.The present data indicate that operators who have completed a basic sUS course perform US-guided biopsies similarly whether using AR US or sUS. However, most students preferred the AR US technique and the learning curve was steeper when using AR US. Further development of AR-based techniques may shift the equilibrium towards broader use of AR US. This evolution should be accompanied by innovation and research.


The target range of Tac C0 has been remarkably changed, with a target as low as 3–7 ng/ml in the 2009 European consensus conference and a target of 4–12 ng/ml (preferably to 7–12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation.Tacrolimus trough levels  with a median age of 36.3 (20–44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7–12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR.p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4–7 ng/ml in the first month . Every 10% increase in TTR was associated with a 28% lower risk of AR .In the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4–7 and > 7 ng/ml (0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.Gaining and maintaining Tac CThe online version contains supplementary material available at 10.1186/s12882-023-03188-0. Acute rejection (AR) is a major risk factor for chronic nephropathy and graft loss after renal transplantation (RT) , 2, and 0) [0 has changed remarkably, with a target as low as 3–7 ng/ml in the 2009 European consensus conference [Maintaining adequate levels of immunosuppressive medication is essential to prevent AR. Tacrolimus (Tac) is the mainstay of immunosuppression following renal transplantation (RT). It has a narrow therapeutic index, and large interpatient and intrapatient pharmacokinetic variability . Hence, 0) . Over thnference .Time in therapeutic range (TTR) was defined as the percentage of time within the therapeutic range over time. In addition to assessing therapeutic trough levels, recent studies have reported that Tac TTR may be a potential prognostic indicator in RT –12. A lo0, especially in the early posttransplant period, when Tac concentrations greatly vary because of the considerable physiological change. This may cause an increased incidence of rejection [At our institution, national or local guidelines on the Tac target range have not yet been determined. There are inconsistent Tac target levels among physicians. This might lead to difficulties in monitoring and maintaining a stable Tac Cejection .0, TTR with AR in the first month following transplantation.Our study aimed to investigate the relationship between the mean Tac C0, TTR, incidence of AR, and the correlation between the mean Tac C0, TTR with AR during the first month.In this retrospective study, we used medical records to investigate the mean Tac CWe carried out a retrospective study including one hundred and sixty Vietnamese patients who underwent RT. Data from the patients were obtained between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Patients between the ages of 18 and 75 years who received a single-organ renal transplant from either a living donor or a deceased donor were eligible, and the patients received Tac as an immunosuppressive treatment. The exclusion criteria were retransplant patients and patients who were not followed up for at least 6 months. A flow chart of patient’s selection was showed in Figure The immunosuppressive protocol followed in our institution consisted of triple drug therapy consisting of tacrolimus, mycophenolate mofetil (MMF) and steroids. The induction therapy included basiliximab 20 mg  on Day 0 and Day 4 after transplantation, and 500 mg intravenous (IV) methyl prednisolone (Solu Medrol®: Pfizer) pre- and 12 h postoperatively. Oral tacrolimus  was started the night before transplantation 1 day with a dose of 0.1 mg/kg/day administered in two divided doses. Subsequent doses were adjusted based on clinical evaluation and whole blood levels. Mycophenolate mofetil  was started with tacrolimus at a dose of 1 g twice a day and the patients’ doses were adjusted to lower doses in the presence of diarrhoea or prolonged fever. The next IV dose of steroids were decreased by half in consecutive days to 40 mg/day within one to two weeks posttransplant. Oral prednisolone (15 mg/day) was initiated right after and was tapered every week to a maintenance period of 5 mg/day.Tac whole blood concentrations were determined using a chemiluminscent microparticle immunoassay . The limit of detection was 1.5 ng/ml. The correlation coefficient of > 0.90 for the specimens between 2.0 and 30 ng/ml. The precision of ≤ 10% of the total coefficient variation (CV). Tac trough concentrations were collected prior to the morning doses. Frequency tacrolimus assays were performed 5 times in the first week, three times in the second week, and every week in the third and fourth weeks, as well as when there were clinical or biochemical parameter abnormalities.0 in the first month was 7–12 ng/ml. The Rosendaal linear interpolation method was used to calculate the TTR [0 and the TTR was calculated by summing the time during which the value fell within this target ml during the first month.According to the second European consensus report, the goal Tac C the TTR . The linIn the group of patients developing AR, all the Tac levels and TTR prior to the AR diagnosis were obtained. In the patients with no AR, all the Tac levels and TTR during the first month were used in the analysis.Assessment of the immunologic risk was based on KDIGO 2009  and the Acute rejection (AR) was suspected when the serum creatinine increased by > 25% of the baseline value. A suspicion of AR in the absence of other possible causes of acute kidney dysfunction promoted a kidney biopsy, and biopsy-proven AR was classified according to the Banff classification , excludiStatistical analyses were conducted in RStudio software. Variables with a normal distribution are expressed as the mean ± standard deviation (SD) and those with an abnormal distribution are expressed as the median and interquartile range (IQR). Categorical data was presented as percentages. The Wilcoxon test was used to compare TTR between two groups: AR and no AR. The significance value of the difference in the curves was assessed by the log-rank test. A multivariate Cox proportional hazard model was used to evaluate the effect of the Tac trough level and TTR on AR. The adjusted factors in the multivariate model included donor age, recipient age, sex, dialysis history, and immunologic risk. P values of < 0.05 were considered statistically significant.± 6.1 months. Almost all donors were living people. Glomerular disease was the most common pretransplant kidney disease in our population (> 90%). The patients’ general characteristics are presented in Table A total of 160 adult patients (113 men and 47 women) underwent RT and were treated with Tac in our centre between January 2018 and December 2019. The mean time of follow-up was 12.1 The AR characteristics are shown in Table 0 were in the subtherapeutic range of 7–12 ng/ml. There was only 30,4% of the Tac C0 within the predefined target during the first month.In the first month, a total of 1725 blood samples were used for the determination of Tac concentrations, and the values were recorded. The mean number of samples per patient was 10.8 (range 4 to 16)  patients experienced AR. The median time to AR was 5 days (range 3 to 30 days). The number of patients who developed AR in the < 4, 4–7 and > 7 ng/ml groups were 3 (17.6%), 9 (15.5%) and 2 (3%), respectively. Among 19 patients in the group with Tac Cp = 0.0131). On the other hand, no statistical significance was noted in the incidence of AR between an average Tac level < 4 ng/ml and Tac level of 4–7 ng/ml by the first month .Table Using a therapeutic range of 7–12 ng/ml, the median 1-month TTR was 31.5% . The difference in TTR between AR and no AR in the first month is shown in Fig. In multivariate Cox proportional analysis that was adjusted for other covariates, there was a marked decrease in the risk of AR in the first month with a successively higher mean TTR. For each 10% increase in TTR, there was a 28% reduced risk of AR   is a common complication in renal transplantation and is associated with reduced graft survival . Monitor0 in the renal transplant recipients, especially in the first month. Our results also demonstrated a strong correlation between a higher Tac TTR and a lower AR in the first month after transplantation, in addition to the association between Tac C0 and the risk of AR. Currently, Tac TTR has been thoroughly investigated as an alternative indicator to quantitate immunosuppression adequacy and that Tac TTR provides a longitudinal assessment of overall drug exposure [0 early and maintaining it within the threshold of 7–12 ng/ml. The idea that TTR might function as a potential indicator for TDM Tac is also supported by this result.Our study found that Tac levels > 7 ng/ml were associated with an 86% decrease in the risk of AR compared with that of 4–7 ng/ml in the first month . This result is line with the Symphony trial  and Chuaexposure , 12. In exposure , 12. But0 and median TTR, especially TTR was only 10% in AR cases compared to 37% in the no AR cases (p = 0.015). This pattern underlines the necessity of better Tac dose monitoring for specific patients after RT.In our study, the incidence of AR was 8.8% in the first month following transplantation. Compared to other recent studies, this result was thought to be higher , 21. The0, TTR with AR in renal transplantation patients in Vietnam. The research was also carried out at one of Vietnam’s largest organ transplant centers, therefore, the results of this study would have a significant impact on clinical practice. On the other hand, there are some limitations in this study. First, due to its retrospective nature, we could only establish the association between TTR and AR. This finding should be confirmed in a prospective assessment. Additionally, our study did not investigate the association between Tac levels and other safety outcomes after RT, such as infectious disease complications  or new onset diabetes after transplantation. However, these complications usually occur for a long-term, over 6 months after RT.To best of our knowledge, this is the first study that showed the association between Tac COur study found a significant association between Tac trough concentration and AR. Higher Tac levels and TTR might reduce the incidence of AR in the first month. Monitoring and maintaining a suitable and stable tacrolimus (Tac) trough level in the early post transplantation is essential for adequate immunosuppression in RT.Below is the link to the electronic supplementary material.Supplementary Material 1


Objectives: The objective of the study was to understand the current prevalence and associated risk factors of Allergic Rhinitis and Eczema in India among 6-7-year-olds, 13-14-year-olds and in their parents/guardians for newer directions to health care providers, policy makers and academicians.The Global Asthma Network phase I study in India aimed to study the prevalence, time trends, and associated risk factors of allergic rhinitis and eczema among 6-7-year-old, and 13-14-year-old school children and their parents. Cross-sectional, multicenter study using self- and parent-administered questionnaire among randomly selected school children aged 6 to 7 years from 8 centers and 13 to 14 years from 9 centers and their respective parents/guardians across India.P < .001) declining time trend since the International Study of Asthma and Allergies in school children phase III in 2002-2003. Among 13-14-year-olds, AR (P < .01) but not eczema showed a significant temporal decline. Coexisting atopic condition, parental history of atopy, and some environmental factors consistent with previous studies were significant risk factors among children and adolescents. AR or eczema in either parent strongly predicted the same atopic condition among their adolescent offspring. Among adults, coexisting atopic condition was the strongest predictor of either AR or eczema.Prevalence of allergic rhinitis (AR)  among 20,084 6-7-year-olds (children), 25,887 13-14-year-olds (adolescents), and 81,296 adults/parents was 7.7% (7.4%-8.1%), 23.5% (23.0%-24.1%), and 9.8% (9.55%-9.96%) and that of eczema was 2.5% (2.3%-2.7%), 3.5% (3.27%-3.71%), and 9.9% (9.7%-10.1%), respectively. Among 6-7-year-olds, AR and eczema showed a significantly (There is a slight declining time trend of AR and eczema in India over 2 decades among children and adolescents. Nearly 10% of Indian adults suffer from AR and eczema. Although genetic factors had the strongest association for AR and eczema among all age groups, certain early-life and environmental exposures need consideration to devise preventative strategies. The Global Asthma Network (The GAN)In 2017, the GAN-India phase I study was initiated in 9 Indian cities to understand the current prevalence of asthma, AR, ARC, and eczema in 6-7-year-olds, 13-14-year-olds, and their parents/guardians. In this article, we report the prevalence, time trends, and risk factors for AR, ARC, and eczema among the 3 study groups.The study protocol and methodology of GAN are described in an earlier publication.In accordance with the GAN protocol, the targeted sample size at each center was 3000 6-7-year-olds and 3000 13-14-year-olds along with their parents/guardians. This sample size gives sufficient power to detect a 5% difference between 2 centers with 99% certainty (at 1% level of significance).The research tool used was the standardized GAN questionnaire with few India-specific questions added with prior approval from the GAN committee. The questionnaire was developed in English and translated into vernacular languages , and was validated with back-translations. English and/or vernacular questionnaires were used as per the school’s preference.The study team included field investigators and data entry operators from all 9 centers who were trained in the study procedures and data collection methods, at IIHMR, Jaipur.The study was conducted with due permission from the head of the school and with the help of a study coordinator and class teacher of the classrooms that contained children from the required age groups. The study was introduced as a health-related survey without mentioning the words asthma or allergy.A passive informed consent process was implemented as per the GAN protocol. Parents were asked to telephonically contact the study team member if they wished to refuse participation. Such students and their parents were excluded from the study.On the predesignated date and time, the study team visited the classrooms, distributed the questionnaire, and recorded the height and weight of the students. The adolescent group self-responded to their questionnaire at school if their parents had consented. They took the adult questionnaires home for their parent(s)/guardian(s) to complete. The younger age group (6-7 years) took both the child and adult questionnaires home. The parents/guardians completed the questionnaire both for their child/ward and for themselves. All questionnaires were submitted back to the respective class teacher. The study team then collected the completed questionnaire from the teacher. The parent and child questionnaires were given the same code number to study familial correlations. The study team resolved any discrepancies or missing data by contacting the parents through the school authorities.,The defining criteria for AR and eczema were as per those used in the ISAAC-Global publicationsCoding of the data and data entry were done as per the GAN protocol. The data were entered by the respective centers, except for Kottayam, for which the entry was done by the National Data Collection Center. Ten percent of the data was double entered by IIHMR for quality checks, with a permissible mismatch of up to 2.0%. Any discrepancies beyond that were mutually resolved by the IIHMR team and the respective center. Consolidated data from all centers were sent to the GAN global center in Auckland, New Zealand, for initial quality check, and subsequently to the main data center in London, United Kingdom, where the data were rechecked. The clean data set was locked and used for analysis.Using SPSS , descriptive analysis and charts were used to describe demographic characteristics, prevalence rates of different symptoms, and health-related data. Continuous variables were presented using N, mean ± SD, and categorical variables were presented as frequency and percentage. Bivariate and multivariate analyses were performed to estimate the impact of environmental and health-related factors for presence of AR, ARC, and eczema.t test for continuous variables. Results of chi-square tests were presented as odds ratios (ORs) with 95% CI. Unadjusted P values less than .05 were considered significant and were further included for multiple comparisons. Multivariate analysis was performed using binary logistic regression model to identify the variables associated with the presence of AR/ARC, eczema, or asthma. The results were presented using adjusted ORs and 95% CIs.Bivariate analysis was performed using chi-square tests for categorical variables and student P value of less than .05 was considered statistically significant.Prevalence of current AR and eczema as reported in ISAAC phase I, phase III, and GAN were compared using chi-square test. A Parent and children data sets were merged to analyze parental history as a risk factor for AR and eczema in children. The presence of current symptoms was correlated with the environmental risk factors to determine associations. Data from ISAAC phase I were extracted from the data available on the ISAAC Website, and data for phase III were extracted from the data published by Singh et al.The age-specific GAN questionnaire was administered to 23,947, 26,808, and 81,798 participants, respectively, for 6-7-year-olds, 13-14-year-olds, and parents of both age groups from across 8 centers for 6-7-year-olds and 9 centers for 13-14-year-olds .Table IGThe response rates for the 3 age groups were 84%, 97%, and 99%, respectively. Male (M) to female (F) ratio of the responses was 52:48, 49:51, and 49.8:50.2, respectively, for children, adolescents, and adults.P < .0001). The prevalence of ARC was 2%  and was higher among boys . The prevalence of AR among 13-14-year-olds was 23.5%  and that of ARC was 8.43%  with similar sex distribution. Among the adult population, the prevalence of AR was 9.8%  with no sexwise difference.The total and centerwise prevalence of AR, ARC, and eczema for all 3 age groups is shown in P < .001) in 6-7-year-olds and 3.48%   among 13-14-year-olds. Prevalence of eczema among adults was 9.9%  without any sex difference.Prevalence of eczema was significantly higher among boys in both student groups, 2.5%  . Eczema in adolescents did not show a statistically significant decline.Time trends in AR, ARC, and eczema from ISAAC-1, ISAAC-3, and GAN are depicted in P = .007). Among adolescents, 1.3% and 0.6% had moderately severe and severe AR, respectively, without any sex difference.Labeled disease condition, severity, and morbidity for eczema are presented in A and B), A and B), and A and B) for children, adolescents, and adults, respectively. Complete analysis of the associations with unadjusted and adjusted OR and factors that were protective is given in www.jaci-global.org. Significant associations with any coexisting atopic conditions, parental history of atopy, and environmental factors for AR and eczema with adjusted OR are given in Among 6-7-year-olds, risk of AR significantly increased with presence of coexisting asthma and eczema. Risk of AR was significantly high if either parent had asthma or AR or eczema. Among adolescents, AR was associated significantly with coexisting asthma and skin problems ever but not with eczema. Parental AR was positively associated with AR in adolescents. Among adults, AR significantly increased with coexisting asthma and eczema. Nongenetic risk factors for AR among 6-7-year-olds were premature birth, laying on sheepskin during infancy, consumption of medicines, paracetamol, or antibiotics during infancy, ever had pneumonia, and presence of moisture or damp spots in house. Among adolescents, AR was associated with increase in symptoms after consumption of banana, watching television for more than 1 hour per day, and use of paracetamol during the past 12 months.Among adults, AR was significantly associated with use of nebulized medications in the past 12 months, presence of moisture or molds in the house, use of air-conditioner at home, use of mosquito coils/repellants, smoking tobacco ever, and fast-food consumption in the past 12 months.Frequent nasal symptoms, presence of parental AR, or eczema in either parent was significantly associated with eczema among 6-7-year-olds. Among 13-14-year-olds, eczema was significantly associated both with coexisting asthma and with AR. Presence of parental eczema was significantly associated with the 13-14-year-olds having eczema. Among adults, eczema was associated with presence of coexisting asthma and AR. Environmental associations for eczema among 6-7-year-olds were use of antibiotics during infancy, intrauterine exposure to farm animals, use of air-conditioner at home, and meat consumption during the past 12 months. Among adolescents, eczema was significantly associated with more than 1 hour of watching television per day, presence of cat in the home during the past 12 months, more than 1 hour spent on computer per day, consumption of soft drinks in last 12 months, passage of heavy trucks through the street, and current use of paracetamol. Environmental factors for eczema among adults included presence of moisture and damp walls in the house, current use of tobacco, smoking water pipe at home, and use of mosquito coils and repellants or incense sticks at home.The GAN phase I study explored the prevalence of AR and eczema among 127,309 children, adolescents, and their parents/guardians among 9 geographically spread cities and is one of the largest studies reported in India during the last 2 decades.The prevalence of AR in India among 6-7-year-olds and 13-14-year-olds was 7.7% and 23.5%, respectively. The findings from the GAN study for the Bangkok region have shown a prevalence of 38.2% and 48.8%, respectively, for these age groups.P < .001) in comparison to ISAAC phase I. GAN phase I done almost 2 decades after ISAAC phase III has shown a significant decline in comparison to the ISAAC phase III. These time trends are consistent with the findings from global data and that from Asian countries as per findings of GAN phase I for AR for both children and adolescents reported recently.The ISAAC phase III conducted in 2002-2003 had shown a significant increase in prevalence of AR and ARC among the 6-7-year-olds and the 13-14-year-olds , adolescents (12.5%-38.4%), and adults (5.1%-14.9%) across India. Eczema also varied between 0.8% and 6% for children, 1.4% and 5.4% for adolescents, and 4.5% and 14.9% for adults. This heterogeneity among the centers is expected because India is a very large country with wide variation in geography, climate, genetics, and sociocultural and dietary practices, which may influence the prevalence.,,Strongest risk factors for AR among 6-7-year-olds were coexisting asthma and eczema with a 5.7-fold and 2.6-fold increased risk, respectively, reiterating that asthma, AR, and eczema are part of a single disease complex and often coexist.Among children, AR was strongly associated with all 3 atopic conditions in parents but among adolescents, only parental AR increased the risk by 50%. For eczema in children, parental eczema and parental AR were a risk factor but among adolescents, it was only parental eczema but not asthma or AR that shared an increased association with eczema by 94%. This indicates that parental AR or eczema is a strong predictor of whether their adolescent children will develop AR or eczema, and ours is probably the first study to show this.,Previous studies have reported premature births as a protective factor for AR,Among adolescents, consumption of banana was the most significant nongenetic association for AR. This was an India-specific question that substantiates practicing clinicians’ observations of the role of banana, as a common trigger in India. Another India-specific question about the presence of water-coolers in the house showed increased association with AR among adolescents. This may possibly be due to fungus growing in the improperly maintained water-cooler. Use of paracetamol in the past 12 months and watching television were risk factors consistent with the ISAAC phase III observations.Among adults, India-specific questions added on indoor air pollutants such as mosquito coils, incense sticks, and mosquito repellants yielded significant association and are modifiable factors providing scope for intervention.,Increased risk of eczema among 6-7-year-olds associated with use of antibiotics during infancy is consistent with existing literatureThe use of a standardized protocol and questionnaire, 3 different age groups, large sample size spatially distributed across the geography, and addition of India-specific questions are some of the key strengths. Availability of parent and child data allowed us newer insights into the role of genetics and predictors of AR and eczema, which was not possible in the studies that were part of ISAAC.The study was limited to urban cities only. This was a self-reported, questionnaire-based study and lack of standard terminology in colloquial languages for terms such as “hay fever” and “eczema” may possibly be a limitation despite our best efforts to validate the translations.In India, high prevalence of AR among adolescents and high prevalence of AR and eczema among adults with strong familial associations need due consideration for early diagnosis and proper management.The prevalence of AR and eczema in India has declined among the 6-7-year-olds and 13-14-year-olds over the past 2 decades. Yet, about a quarter of the adolescent population in India suffers from AR. This is indeed alarming and needs attention. Adolescence is a vulnerable age, and presence of an adverse health condition can significantly affect overall development. Parental AR or eczema is a strong predictor of AR or eczema, respectively, among adolescents. India has a very large population of adults who suffer from AR and eczema, which needs to be diagnosed and managed appropriately. Family history and early-life exposures are strong risk factors for AR and eczema in children.