Male moths aiming to locate pheromone-releasing females rely on stimulus-adapted search maneuvers complicated by a discontinuous distribution of pheromone patches. They alternate sequences of upwind surge when perceiving the pheromone and cross- or downwind casting when the odor is lost. We compare four search strategies: three reactive versus one cognitive. The former consist of pre-programmed movement sequences triggered by pheromone detections while the latter uses Bayesian inference to build spatial probability maps. Based on the analysis of triphasic responses of antennal lobe neurons , we propose three reactive strategies. One combines upwind surge (representing the On response to a pheromone detection) and spiral casting, only. The other two additionally include crosswind (zigzag) casting representing the Off phase. As cognitive strategy we use the infotaxis algorithm which was developed for searching in a turbulent medium. Detection events in the electroantennogram of a moth attached to a robot indirectly control this cyborg, depending on the strategy in use. The recorded trajectories are analyzed with regard to success rates, efficiency, and other features. In addition, we qualitatively compare our robotic trajectories to behavioral search paths. Reactive searching is more efficient (yielding shorter trajectories) for higher pheromone doses whereas cognitive searching works better for lower doses. With respect to our experimental conditions (2 m from starting position to pheromone source), reactive searching with crosswind zigzag yields the shortest trajectories (for comparable success rates). Assuming that the neuronal Off response represents a short-term memory, zigzagging is an efficient movement to relocate a recently lost pheromone plume. Accordingly, such reactive strategies offer an interesting alternative to complex cognitive searching. The moth mating race is a suitable model case for studying the efficiency of various search strategies and to compare them to real-world behavior. All there is to guide olfactory navigation are simple sporadic clues, i.e., single pheromone detections. Thus, a pheromone seeking male relies on a specifically adapted behavior where action selection is triggered by simple perceptional events. They switch between stereotypical movement sequences, as, for example, upwind surge and crosswind casting. This behavior can be either a consequence of cognitive processing or a reactive reflex of fixed action patterns. Suggesting a direct relationship between neuronal central activity and such action patterns, we combine and implement them as reactive strategies. We also employ infotaxis, an artificial intelligence algorithm specifically developed for searching in turbulent odor plumes. Using these strategies in cyborg experiments, we obtain and compare the resulting search trajectories. Our results indicate that complex, computationally expensive search strategies like infotaxis are not necessarily better than simple reactive ones. With respect to our set-up, reactive searching yields the shortest trajectories if and only if it includes a crosswind zigzagging phase that represents a short-term memory. Thus, already a minimal bit of simplistic memory can produce very efficient goal-directed behavior. The efficiency of male moths searching for females is astonishing. In spite of serious difficulties, as, for example, large distances, sharp time constraints, and sparse discontinuous clues, their olfactory pheromone system usually guarantees a successful encounter This mating race is not only fascinating in itself but also particularly convenient to study the chain linking perception to action, and for the investigation of search tasks in general. The advantages are the rich adaptive behavioral repertoire of insects generated by a relatively simple neuronal system reactive search strategies have been suggested and modified An important factor is the olfactory stimulus cognitive strategies, e.g. A powerful alternative to reactive searching is the more sophisticated and computationally rather expensive approach of using Such experimental tests of theoretical models are particularly important for applied research as they point out real-world issues and limitations that mere simulations cannot account for. This is true for both studies involving reactive Agrotis ipsilon mounted on a mobile robot sp) combines surge and arithmetic spiral casting, (za) and (ze) combine surge and a two-step casting sequence composed of crosswind casting, i.e., zigzagging followed by arithmetic or exponential spiraling, respectively. The single movement sequences are motivated by biological findings on behavioral insect data: straight upwind surge Using such an approach, we compare the strategies detailed above: reactive versus cognitive searching in dependence of the stimulation strength for a turbulent air flow. Our cyborg, a male moth We consider in this article the following questions: is complex cognitive searching superior to using simple reactive strategies? What is the influence of the stimulus strength? How can the resulting search trajectories be characterized and compared? Do they show common features and how do they relate to behavioral data? We expected a clear and overall predominance of infotaxis since the algorithm involves memory and learning, and it has been proven to be very successful in computer simulations We first present the biological motivation of the implemented reactive search strategies. We then detail the results of using these strategies, as well as the infotaxis algorithm, in cyborg experiments. On the one hand, we focus on basic features as success rate and efficiency, expressed by the corresponding trajectory lengths. On the other hand, we also aim at a more detailed characterization of these search paths, including a qualitative comparison to behavioral data We first detail the analysis of the neuronal MGC recordings. Subsequently, we relate the different regimes therein to the reactive search strategies used in the cyborg experiments. After a brief introduction of the infotaxis strategy, we present the results of comparing various search strategies in cyborg experiments. Finally, we relate and compare patterns occurring in our cyborg trajectories to those of walking moths published in We consider the electrophysiological MGC recordings of 8 multiphasic neurons and 6 monophasic neurons , part 1,For comparison, we also analyze monophasic MGC responses to pheromone stimulation, shown in sp strategy neglects the Off while the other two strategies (za and ze) comprise a zigzag casting sequence representing the Off in our multiphasic neurons . Note that the cyborg stops zigzagging after a fixed period of 19 s (if there is no further detection): as we record from the antenna and not from the MGC, we do not have access to the length of the Off. Our za and ze strategies combine zigzagging with either arithmetic or exponential spirals As initial movement, we choose arithmetic or exponential spiraling which represents baseline firing. We assume that each detection event initiates a straight upwind surge representing the On. If there is no subsequent detection, the movement changes either into Off zigzagging followed by baseline spiraling, or it directly switches back to baseline spiraling  and exploration . The exploration mode predominates if there is nearly no information available. Long periods of time with no odor encounter broaden the posterior distribution and compel the agent to explore the environment in large patterns. On the contrary, if many detections indicate that the source is close, the exploitation mode triggers more localized movements. Starting from a prior probability distribution for the location of the source, the agent accumulates information while exploring its environment. Both odor detections and non-detections contribute to the ongoing update of the estimated spatial probability distribution. Infotaxis has been shown to function very well in computer simulations , 85% (za), and 84% (ze), averaged across different doses. Cognitive searching yields a sightly higher success rate of 93% (it) trials without stimulation is 73%. These are not called false positives, since infotaxis is supposed to be successful even without stimulation . More details are given in ze path lengths obtained for varying doses, as well as between sp, za and ze path lengths obtained for the maximum dose are particularly small because these trajectories are close to the minimum length.A global ANOVA yields a statistically significant difference for both strategy and dose  together with particularly long trajectories.mal path  coincidemal path . For cogsp histogram shows one single peak representing the upwind surge associated with the On response while the za histogram exhibits two additional peaks at approximately za and ze histograms . In terms of reactive trajectories, however, the number of turns slightly decreases with increasing dose . Otherwise, in case of stimulated trials, the path length increases with the pheromone doses due to the high number of turns which are related to the exceptionally high number of detections (see subsection Infotaxis) — while the horizontal spread decreases.One might wonder about the low success rate for reactive trials with no stimulation  as the cBombyx mori) walking in a wind tunnel tries to locate a pheromone source (relatively high pheromone concentration) located 60 cm away from the starting position za and ze strategies za and ze trajectories (With ectories .sp), and two more complex strategies including an additional Off zigzag phase following the surge sequence . We applied these reactive strategies, as well as the cognitive infotaxis algorithm, in robotic experiments enabling our cyborg to locate a pheromone source. Reactive searching with Off zigzagging yielded the shortest trajectories, independent of the pheromone dose : (Z)-7-dodecenyl acetate, (Z)-9-tetradecenyl acetate and (Z)-11-hexadecenyl acetate. The stimulation lasted 200 ms. There are 4 to 10 trials for each neuron. Extracellular recordings were performed by inserting two glass electrodes filled with Tucson ringer into the MGC. After amplification the signal was band-pass filtered (0.3 to 5 kHz) and sampled at 16 kHz. Spike sorting (R-package SpikeOMatic) yielded single neuron signals. For more details see Neurons from the macroglomerular complex (MGC) were recorded from male We here analyzed the responses of 8 neurons that exhibited clear multiphasic responses : an exciThe Off occurrence is usually based on an increased firing compared to baseline activity , see 2, 1 CaCl2, 12 NaCl. A silver wire inside the glass pipette served as recording electrode while another wire, the reference electrode, was inserted into the neck. The sensor was approximately 16 cm above the ground. An EAG acquisition board was embedded on the robot. The EAG signal was transmitted wireless via WIFI to a remote computer in order to be used as input for a MGC neuron model. This neuron simulation was performed in real-time (time steps  = 0.01 ms) using SIRENE, a C-based neural simulator (http://sirene.gforge.inria.fr). Neuron simulation, pheromone detection and robot control were performed in separate threads. A graphical user interface (written in Qt/C++) visualized both EAG input and neuron output. For more details see Tethered moths  µl of pheromone solution dropped on its tip, located approximately 16 cm above the ground. We used three different doses: minimum  = 0.1 µg/µl, medium  = 0.3 µg/µl and maximum  = 1 µg/µl of main pheromone component ((Z)-7-dodecenyl acetate). The plume contour (indicated by black dashed lines in http://en.wikibooks.org/wiki/Category:Khepera_III_Toolbox).Our cyborg  had to locate the pheromone source in an arena of 4 m length and 2.5 m width, see We employed three reactive search strategies and one cognitive strategy, namely infotaxis sp strategy) or by crosswind zigzagging (za and ze strategy) as illustrated in za) was generated by ze) results from After each detection, the cyborg received a surge command leading to a straight upwind movement (approximately 5 cm). This was either followed by spiral casting . Track-angle histograms  show the distribution of track-angles, i.e., movement directions: 0 means straight upwind, In total, we performed 428 successful trials using reactive search strategies and 85 successful trials using infotaxis . Ideallyirection  and 5B.


Background: The National Dietary Survey on the Child and Adolescent Population in Spain (ENALIA) provides data to assess the usual micronutrient intake among Spanish infants, children, and adolescents. Methods: Cross-sectional survey (November 2012–July 2014) of a representative sample of Spanish children and adolescents (six months–17 years) (n = 1862). Dietary information was collected using two non-consecutive one-day food diaries (six months–10 years old) or two 24 h dietary recalls (11 years and older) separated by at least 14 days. Estimates were calculated using the Iowa State University method and PC-SIDE software  to account for within- and between-person variation. Results: Usual intake of vitamin D was insufficient in practically all individuals. Vitamin E, folate, and calcium were insufficient, especially from nine years of age, and magnesium and iodine from 14 years of age. The percentage of subjects with insufficient intakes was higher among females. Sodium intake was excessive in a considerable percentage of the population, especially in males, and it increased with age. Finally, over half of children under four years of age had zinc usual intakes that exceeded the Tolerable Upper Level. Conclusion: Vitamin and mineral intake in Spain should be improved, especially in late childhood and adolescence. Nutritional intervention and educational strategies are needed to promote healthy eating habits and correct micronutrient inadequacies in Spanish children and adolescents. Early childhood is the most rapid period of development and following a balanced diet in these stages is essential to ensure optimal growth and development . AdolescDietary surveys provide insight into dietary habits and food intake and help estimate the adequacy of the nutrient intake of different groups in a population, monitor their changes and develop nutritional interventions. One of the challenges in dietary surveys is the assessment of usual intakes, i.e., the long-term dietary information. Single or repeated 24 h dietary recalls or food records are used for dietary assessment in large epidemiological studies  because Until now the reference study on children and young people in Spain was the enKid study. It was conducted between 1998 and 2000 on 2855 Spanish children and adolescents aged between two and 24 years . DietaryThe ENALIA study  is a cross-sectional survey that was carried out in Spain and sought to collect accurate food consumption data in children and adolescents in a way that is consistent with other European countries ,14,15. TThe ENALIA study was a cross-sectional survey conducted in Spain on a national sample of children and adolescents (six months–18 years old). The design, protocol, and methodology of the ENALIA study have been already described elsewhere ,17 and fThe study was conducted according to the guidelines laid down in the Declaration of Helsinki. Depending on the age of participants, information was given to parents, tutors, or other legal representatives, and consent and assent from each participant were obtained before proceeding with the study interviews. The Spanish Agency of Consumption, Food Security, and Nutrition (AECOSAN), belonging to the Spanish Ministry of Health, Social Services and Equality, approved the study. In accordance with the Spanish Ethical Review System, ethical approval was exempt from ethical review because this is a population-based survey, no intervention were done, no human biological samples were collected, and all data from the study were anonymized and de-identified.The target population was people under 18 years old living in households in Spain. The ENALIA study began in November 2012 and ended in July 2014. Institutionalized populations were excluded. Recruitment was done via home visits and for children under four years of age, also in kindergartens, since in Spain they are only for the day care of the children. Subjects were randomly chosen from all 17 autonomous regions in Spain, according to a random multistage sampling procedure, considering census section and municipality, population size , age, and sex. To capture the inter-seasonal variability in consumption patterns, subjects were uniformly distributed over the four different seasons, and the schedule was organized to capture an adequate proportion of weekdays and weekend days at the population group level. The sample was also distributed uniformly over the weeks in a month. The recruitment process included five contacts: an initial contact with household by phone or at nurseries/kindergarten (for children under three years of age), a second contact by letter , two more contacts by phone , and a fifth final contact with a household visit .The ENALIA final sample included 1862 children aged six months to 17.9 years. The participation rate was 68.9%. Dietary information was collected using two different methodologies depending on the child’s age: two non-consecutive one-day food diaries separated by at least 14 days, for children from six months to 10 years of age or two 24 h dietary recalls, separated by at least 14 days, for adolescents (11 years old and over). In younger groups of children (under 11 years old), parents and caregivers were responsible for completing the food diaries and the other questionnaires, and requested collaboration and/or information from other proxy persons about the child’s out-of-home diet. The recalls were conducted using specific software (ENIA-Soft)  in computer-assisted interviews by trained interviewers and nutritionists/dieticians. Food diaries were also recorded using this software, since guided the interviewer during data collection, facilitating the homogenous collection of information. The software included a database with coded foods, a database with standard recipes, a database with weights and household measurements, and a database with pictures and portion weights from a validated photographic food atlas for Spanish children and adolescents . The picNutrient intake was calculated from dietary records/recalls using the Spanish Food Composition Tables  completeA general questionnaire asked about sociodemographic data, such as the birth date of the participant, place/country of origin of the participant and his/her parents, academic level and profession of parents, and about the health status of the participant .Anthropometric data of the participant were measured at the interviewee’s home by trained interviewers and following standardized procedures . A stadiSample weight factors for each participant were calculated to account for nonresponses and to weight the sample to known population demographic characteristics. Since the average intake of a small number of days of dietary record/recall (observed intakes) does not adequately reflect the usual intake, it is necessary to statistically model the dietary data to eliminate day-to-day variation in food consumption . We usedTo assess vitamin and mineral adequacy, the Estimated Average Requirement (EAR) cut-off point method was used . We usedThe plausibility of energy intakes was assessed using the Goldberg’s cut-off method  updated p value < 0.05 indicated statistical significance. The normality of the distribution of age, anthropometric and EI/BMR data was checked using the Kolmogorov–Smirnov test. Differences between males and females were examined with the Student’s t test or the Mann-Whitney U test, depending on whether or not the data were normally distributed. Categorical variables were compared using the χ2 test. Dietary intakes of the participants were expressed as the means and standard deviations, medians, and 5th and 95th percentiles.Statistical analyses were performed using the statistical software package SPSS version 20.0 for Windows. A Characteristics of the studied sample are shown in The percentage of under-reporters ranged from 0.6% (children aged six to 12 months) to 19.8% (adolescents aged 14–17 years). On the other hand, overestimation was higher in younger children (16%) and lower in adolescents (0.4%). The data presented in the rest of this report have not been adjusted for under-reporting.The usual intakes (from food and beverage sources only) of vitamins and minerals are presented in Regarding the usual intake of minerals, the prevalence of inadequate intakes in children below four years of age was low (<5%), except for iron in children between six and 12 months and for iodine in children between one and three years, where a subset of infants (10.9%–14.2% for iron and 11.0%–7.8% for iodine, The usual intake of minerals exceeded the ULs for sodium in a high percentage of children and adolescents, and the prevalence of higher usual intakes increased with age . In addiThis paper provides recent estimates of the vitamin, mineral, and trace element intake distributions, from food and beverage sources only, in a representative sample of Spanish infants, toddlers, children, and adolescents. The usual micronutrient intakes in the ENALIA study meet or exceed their requirements, except for those of vitamin D, which was practically insufficient in all individuals, and vitamin E, folate, calcium, magnesium, and iodine, especially in adolescents and females. Sodium intake is excessive in a considerable percentage of the population, especially in males, and increases with age. Finally, the usual intake of zinc exceeds the UL in children less than four years of age.Data on intake distributions in children, corrected for the day-to-day variation, are very scarce in Europe . As for Both food diaries and dietary recalls are prone to under-/over-reporting, and there is debate about whether or not to eliminate misreporters in dietary studies, since the exclusion of potential misreporters may create a biased sample. The exclusion of under-/over-reporters might have induced selection bias since the misreporters might have a special food choice or eating behavior. In addition, under-reporting includes both under-recording and under-eating, and some over-reporters could eat much more than usual during the period of study as well. It has also been suggested that low energy reporting may be just as common among plausible energy reporters as among those defined as under-reporters , so thatThis study highlights the very low intake of vitamin D, which is insufficient in all age groups and sexes, and the fact that almost all individuals have intakes that are at risk. Vitamin D deficiency is a worldwide health problem, and similar data have been described in infants in the Netherlands , FinlandThe usual mean vitamin E intakes were less than the EARs in some subgroups of children, especially those over nine years of age, similar to what was observed in other toddlers and preschoolers  and in aFolate intake is inadequate in a high proportion of children and adolescents over nine years of age . The risRegarding minerals, the risk of inadequate calcium intake is especially high in children over nine years of age and is even higher in females . DiethelAs for iron intake, the EARs are exceeded in almost all subgroups, except for a small but important subset of six- to 12-month-old infants whose usual intakes were below the EAR (10.9% in males, 14.2% in females, On the other hand, the percentage of adolescent girls with inadequate iron intake is low relative to other studies, although differences may be due not only to different eating patterns of children and adolescents within Europe , but alsThe usual intake of sodium exceeds the UL in a considerable percentage of children in all age and sex groups, although the prevalence of excessive intakes is higher in males . SimilarThe usual magnesium intake is insufficient in 63.5% of adolescent males and 81.8% of females . The medSome small but important subsets of children have a high risk of inadequate intake of iodine, and the risk is highest in adolescent females over 14 years . Other sFinally, the usual zinc intake exceeds the UL in children up to four years of age, although there was a group of girls over nine years old with intakes at risk of deficiency (9.2% and 6.3% in girls between nine and 13 years and over 14 years, respectively, Our study has some limitations and strengths. First, the food composition tables may not accurately reflect the nutrient composition of the food. It is appreciated that there is variability in the composition of foods, likely due to differences in season, cultivar, or variety. On the other hand, the Spanish Food Composition Tables used included enriched/fortified foods commonly available in Spain, and additional composition data for specific brands were taken into account. Fortification values can differ between countries, so data from food composition tables from other countries might not be adequate. Our study did not account for the use of supplements of vitamins and minerals, so the results of this study are limited to the dietary intake of micronutrients. Although parents may be reliable reporters of their children’s food intake at home, meals out of parental control are prone to being misreported, as are the estimation of their portion sizes . FinallyThis paper provides recent data on the dietary vitamin and mineral intake from food and beverage sources of Spanish children. Public health initiatives should ensure that children and adolescents follow an adequate, balanced diet because the health behaviors adopted during the early years of life and adolescence can be maintained in adulthood, and improving them would help prevent many chronic diseases related to diet. Such initiatives should include the promotion of a Mediterranean Diet style, including more fish, eggs, cereals, and dairy products which are source of vitamin D, and lowering the consumption of processed foods which are sources of sodium. Additionally, the collaboration between the administration and the industry aiming to reduce more of the sodium content of processed foods is also desirable. Clinical and biological assessment of the nutritional status of a representative sample of Spanish children and adolescents focusing on the micronutrients of concern would seem advisable.


Malignant airway obstruction is a feared complication and will most probably occur more frequently in the future because of increasing cancer incidence and increased life expectancy in cancer patients. Minimal invasive treatment using airway stents represents a meaningful and life-saving palliation. We present a new removable airway stent for improved individualised treatment.in vivo model using two anaesthetised and spontaneously breathing pigs, we deployed and subsequently removed the stents by unravelling the device. The procedures were executed by flexible bronchoscopy in an acute and a chronic setting – a ‘proof-of-principle’ study.To our knowledge, the new airway stent is the world's first knitted and uncovered self-expanding metal stent, which can unravel and be completely removed. In an The new stent was easily and accurately deployed in the central airways, and it remained fixed in its original position. It was easy to unravel and completely remove from the airways without clinically significant complications. During the presence of the stent in the chronic study, granulation tissue was induced. This tissue disappeared spontaneously with the removal.The new removable stent functioned according to its purpose and unravelled easily, and it was completely removed without significant technical or medical complications. Induced granulation tissue disappeared spontaneously. Further studies on animals and humans are needed to define its optimal indications and future use. Benign and malignant airway obstruction (MAO) may affect individuals at all ages. The physicians must think and act differently in each case, depending on the cause, the characteristics of the airway obstruction, and the individual patient. The treatment options are numerous, including interventional bronchoscopy, systemic treatment, and endobronchial and extrathoracic irradiation. The need for optimal individualised treatment is a fact –3.Benign airway obstruction comprises fibrous membrane stenosis, post-infectious granulomas and strictures, tracheobronchomalacia, foreign bodies, and severe haemoptysis. MAO is more frequent in the adult population, expressed either as intrabronchial tumour growth or external tumour compression, not seldom complicated with trachea-esophageal fistulas and airway stenosis . Figure Thermal ablation  or brachytherapy applied with bronchoscopy is often used to treat MAO. Thermal ablation is contraindicated in stenosis caused by pure external tumour compression, often leaving stent therapy as the best choice. There are different types of stents available on the market. Some silicone stents are radiopaque and some are not; deployment needs rigid bronchoscopy and general anaesthesia, but these stents can be removed. Self-expanding metal stents (SEMS) are visible by X-ray; deployment can be performed with flexible bronchoscopy using conscious sedation combined with local anaesthetics. Uncovered SEMS can be difficult to remove because of epithelisation, ingrowth of tumour and granulomatous tissue. This drawback is less pronounced in first weeks after deployment and less a problem in covered stents. Uncovered SEMS are avoided in benign airway disorders and in patients with MAO who have a longer life expectancy. Complications to airway stents are migration within the airways, granuloma formation, mucostasis and pneumonia, mucosal ischaemia and fistulas. This is because of the radial pressure on neighbouring tissue induced by the stent. Complications may also be associated with the underlying condition or comorbidity , 14, 15.Lacking the possibility of removing uncovered SEMS, especially after 6–8 weeks, is a clinically important limitation of the functionality of the stent. Covered SEMS are often used in patients with MAO and short lifetime expectancy –19. FirsThe removable stent used in the two current experiments represents a new type of uncovered self-expanding metal stent made by the memory alloy nitinol . The stein vitro for its mechanical properties and as vascular stent in iliac arteries in sheep in acute and chronic studies, with successful unravelling. The stent is ordered and produced online based on specifications of needs for a specific person and condition. It is produced at GraftCraft AB, Borås, Sweden. The stent is not approved for medical use in humans, but based on this and further studies, this is the plan.The stent is knitted from a nitinol thread. Nitinol is a memory alloy, and the stent thereby belongs to the group of SEMS. There is usually no need for any balloon dilatation after deployment of the stent. The mechanical impact and radial force can be predefined and specified according to the individual needs, which increases the possibilities for successful individualised treatment. Before this study, the new removable stent has been thoroughly tested, in vivo animal study with two spontaneously breathing pigs – ‘A proof-of-principle study’. The procedure was first tested in a phantom model and subsequently in the animal model , safety (adverse events) and the ability to be removed (unravelling characteristics). The study was performed in an acute and a chronic setting using an al model .in vivo animal model with spontaneous breathing anaesthetised pigs. The pigs were acclimatised for 1 week before the studies in the animal research department and fasted overnight before each experiment. Subcutaneous premedication was given (azaperon 16 mg/kg body weight (mg/kg bw), diazepam 0.25 mg/kg bw, ketamine 3 mg/kg bw and 1 mg atropinsulphate). Anaesthesia was given through a venous catheter in a marginal ear vein. Induction consisted of ketamine 3–4 mg/kg bw and sodium pentothal 2–3 mg/kg bw. The pig received a temporary or orotracheal tube for transportation between buildings. Maintenance anaesthesia was given as a continuous intravenous infusion of ketamine, midazolam and fentanyl.We established a novel 2 supply on a nasal tube with an inner diameter of 4.0 mm. Complementary ketamine, midazolam and fentanyl were given when the respiratory rate increased, respiration deepened and/or the eyelash reflex was elicited by finger stroke. Heart rate was kept between 60 and 100 beats/min and blood pressure was kept within 100–120/60–80 mmHg.The orotracheal tube was removed right before the start of the stenting procedure. To achieve spontaneous breathing and open airways, the jaws and tongue were fixed with smooth textile bonds. Adequate oxygenation (oxygen saturation 96–100%) was maintained by 10 l/min OWe used a flexible bronchoscope  for inspection, deployment, unravelling and removal of the stents. The operating theatre was located at the Operating Room of the Future (ORF), which is dedicated to research and development activities. Deployment was facilitated by using a guide wire and an in-house-built introducer. The deployment and removal procedure was documented and guided through bronchoscopy videos and images, X-ray (fluoroscopy) and cone beam CT acquisition.Deployment and accurate placement, subsequent unravelling and complete removal of differently sized stents in differently sized airways in both lungs were performed with a flexible bronchoscope . During Day 1: Deployment and accurate placement of stents, leaving one peripheral (8×20 mm) and one more proximal stent (11×20 mm) in the right (main) bronchus . ThereafDay 14: Bronchoscopy during which the operator grabbed the proximal end of the thread with the forceps, pulled carefully and unravelled the proximal stent as one single thread in one sequence, as described above in the acute study. The distal stent was left behind. The animal was observed in the ACF for another 4 days.Day 18: Bronchoscopy was performed to study the conditions and healing of the proximal right main bronchus after removal of the proximal stent and control of the position and bronchial condition of the residual distal stent.In the acute and at all stages of the chronic study, acquisition of bronchoscopy images and videos were collected, together with X-ray (fluoroscopy) and cone beam CT images. During anaesthesia, the pig showed no spontaneous movement, but showed normal cardio-pulmonary functions and breathed spontaneously during the whole experiment.The Local Ethics Committee of the Norwegian Experimental Animal Board approved the experiments in accordance with the Helsinki Convention for the use and care of animals.The two stents (size 11×20 mm and 14×20 mm) were successfully deployed and accurately placed in the central airways, using a flexible bronchoscope and an in-house-built introducer and guide wire. The stents remained in their fixed positions before they were successfully unravelled and completely removed from the airways, carefully, in one sequence as a single thread . The steDay 1: The two stents were successfully deployed and accurately placed in the right bronchial tree, one in distal position, lobe bronchus (8×20 mm stent), and the other in a more proximal position, main bronchus (11×20 mm stent), using the same instruments and technique as described in the Acute study section.Day 14: The extended thread was immediately found using the bronchoscope, it was grasped with a forceps and the stent was easy to unravel and completely remove from the airways, with the technique described in the Methods section. The stent was carefully pulled out as a single thread in one sequence. The procedure was effective and safe, and was performed without technical or medical complications . The vidDay 18: We observed the same phenomenon in the residual distal stent with occurrence of mucus retention and granulation tissue. At this time, the proximal main bronchus from where the proximal stent had been removed was almost free from mucosal inflammation and granulation tissue. The bronchial wall had recovered almost completely 4 days after removal of the stent  – Day 18The new removable SEMS was successfully deployed and accurately placed in the airways; it expanded in accordance with its purpose and remained in a fixed position, both in peripheral and more proximal parts of the right bronchial tree. It was easy to unravel and completely remove without significant medical or technical complications, regarding both the acute and chronic study. The stent was removed carefully as one single metal thread in one sequence. In this ‘proof-of-principle study’, the stent fulfilled its expected efficacy, safety and feasibility. No other studies with predesigned unravelling, removable and uncovered SEMS are known to date. Inflammatory adverse events and granulation tissue, associated with present available uncovered SEMS, also occurred using the new removable stent. To our experience, this phenomenon was shown to be of the same quality and extent as we have seen with ordinary uncovered stents. We emphasise that after the stent removal, the inflammation and granulation tissue had almost disappeared within 4 days, leaving the bronchial wall in a good recovery state.The current feasibility study was a preclinical proof-of-principle study in presumptively healthy pigs. The results should therefore be interpreted with caution before extended to the treatment of MAO in human beings. The relevance of the animal model for the present hypothesis may therefore be questioned. With respect to the difference between healthy airways of pigs versus MAO in human beings, the findings cannot directly be transferred. Apart from that, the choice of species can be fairly well argued for the main purpose of this initial feasibility study. First, porcine models have been established as reliable animal models for a variety of human lung-related conditions, regarding anatomy and size to genetic and translational medicine, including our own experience –24. TestRemoval of ordinary uncovered SEMS may cause harm to the bronchus and promote bleeding, especially 6–8 weeks after deployment. Covered SEMS can be removed, but also these stents may cause complications due to inflammation, granulation tissue and ingrowth – especially at the proximal and distal ends. In this study, a superficial bleeding occurred after unravelling the stent in the chronic study, which was easily and quickly cleaned by suction and ceased.To sum up, the pros are 1) easy and accurate deployment with the possibility to change stents during the procedure, 2) stents remained in fixed positions in the airways over 18 days , 3) easy unravelling and complete removal of the stent without significant technical or medical complications and 4) pronounced and fast mucosal recovery after removal of the stent. Cons are 1) the occurrence of some mucosal retention and 2) inflammatory granulation tissue, as expected in all commercially available stents to date. The new stent functioned according to its purpose and it seems promising for human use.Area of utilisation may be wide and appropriate. First, uncovered SEMS may maintain airway branch ventilation better than covered or silicon stents, and the new stent may cover all established indications of ordinary SEMS. Second, removable stents may be favourable as short-term or temporary use after interventional bronchoscopy, subsequent extra thoracic radiation or brachytherapy and thereby minimise development of stenosis formation and complicating atelectasis or obstructive pneumonia. The removal of the stent has the potential to further reduce the degree of granulation tissue, thereby achieving an even larger bronchus diameter. Third, the physician would appreciate the opportunity to remove the stent at any time, also during the deployment to guarantee optimal individualised treatment.There may be some additional advantages: one can order the right size, shape and radial force and vary the thread dimensions and characteristics, and knitting characters. The final stent placement and function has a high potential to be optimal because the stent can be changed at any time. In summary, it may lead to an improved individualised endoscopic therapy. Results from human studies are necessary for final conclusions, but the results from the present proof-of-principle study seem promising for human use.The new removable and uncovered self-expanding metal stent was successfully deployed in the central airways of pigs, using a flexible bronchoscope and spontaneously breathing animals. The stents remained fixed in their original positions and were easy to unravel and completely remove from the airways after 14 days, without any clinically significant complications. The removal imposed an almost complete recovery of the inflammatory responses within 4 days. Further studies on animals and humans are needed to evaluate the efficacy, safety and optimal use of the new removable stent in human beings.


Trichoderma. In general, almost half of the variations of transcriptome and protein level are due to translational control. Thus, studies are required to integrate raw information from different “omics” approaches for accurate depiction of translational response of BCAs in interaction with plants and plant pathogens. The studies on translational status of only active mRNAs bridging with proteome data will help in accurate characterization of only a subset of mRNAs actively engaged in translation. This review highlights the associated bottlenecks and use of state-of-the-art procedures in addressing the gap to accelerate future accomplishment of biocontrol mechanisms.Genome-wide studies of transcripts expression help in systematic monitoring of genes and allow targeting of candidate genes for future research. In contrast to relatively stable genomic data, the expression of genes is dynamic and regulated both at time and space level at different level in. The variation in the rate of translation is specific for each protein. Both the inherent nature of an mRNA molecule to be translated and the external environmental stimuli can affect the efficiency of the translation process. In biocontrol agents (BCAs), the molecular response at translational level may represents noise-like response of absolute transcript level and an adaptive response to physiological and pathological situations representing subset of mRNAs population actively translated in a cell. The molecular responses of biocontrol are complex and involve multistage regulation of number of genes. The use of high-throughput techniques has led to rapid increase in volume of transcriptomics data of  Trichoderma is a cosmopolitan and cardinal representative soil microflora of various climatic conditions . Genome sequencing and its annotation in mycoparasitic species have depicted genome sizes of 38.8 and 36.1 Mb for T. viride and of T. atroviride for biocontrol strains, respectively, compared to 34 Mb of T. reesei an industrial strain. Annotation of complete genome depicted a gene pool of 11,800 genes for T. atroviride and 12,400 genes for T. viride, compared to 9,143 genes in saprophytic strain T. reesei. The abundance of gene pool in mycoparasitic strains of Trichoderma genome . Recent studies showed that the gene expression of mycoparasitic T. harzianum and T. atroviride strains changes not only to plant-pathogenic fungi . The interaction of Trichoderma with host plants reprograms not only the gene expression of biocontrol strains but also of its associated host plant . For example, strains of Trichoderma are explored for growth promotion and boosting immune responses, root development, and activation of seed germination or amelioration of abiotic stresses  transcripts were found significantly differentially expressed in mycoparasitic interactions. The differentially expressed transcripts were also investigated during pathogenic attack on Phytophthora capsici, Botrytis cinerea, and R. solani . A comparative account of genome revealed presence of seven chromosomes in industrial strain T. reesei  during the early interaction of T. atroviride with B. cinerea and R. solani were identified .Studies involving translational regulation of gene expression are emerging as a prominent tool for the understanding the regulation of protein abundance in adaptive responses of the host . In the Figure 3). Polysomal profiling discovered in 1960s involves the separation of actively translated mRNAs bound by several ribosomes from free RNA by sucrose gradient centrifugation and then mRNAs can be coupled to northern blot or RT-qPCR or cDNA microarrays, or RNA-seq on a global level  polysomal profiling, (b) ribosomal profiling, and (c) ribosome affinity purification (RAP) .The post-transcriptional events such as translation regulation and protein stability are the principle causes of weak correlations and variations in proteomic, transcriptomic, and genomic data. The associated errors in transcriptome analysis are subjected to arise from the suppression by microarrays which can further impede the identification of active candidate transcripts. On the other side, methods opted for protein staining, limitations associated in visualizing low-abundant and co-migrating proteins seriously hampers proteomic based study. The recent developments in proteomics methods such as use of mass spectrometric (MS) and liquid chromatography (LC) techniques have made quantitative proteomic profiling, currently a driving force for identification of proteins. The highly stable and reproducible performance of mass spectrometers such as Q Exactive hybrid quadrupole-Orbitrap mass spectrometer MS and Triple TOF 5600 MS is capable of identification of both proteomics  and charTrichoderma spp. has accelerated our research on understanding of the behavior of different species of this genus and how the information on their gene pool determines their capabilities and limitations. The genomes of Trichoderma which is known to contain thousands of genes encoding different glycosyl hydrolases, secondary metabolites, antibiotics, lectins with insecticidal properties, and transporters with potential in bioremediation involved in antibiotics biosynthesis, and several other candidate genes , translatome level (ribosome loaded mRNAs) and the proteome is experimentally feasible in a high-throughput way, the integration of these omic technologies is still far away. Systematic global analyses aims at integrating transcriptome, translatome, and proteome level can provide accurate view of widespread adaptive mechanisms of interaction between Trichoderma–plant–pathogen.The genomic comparison of mycoparasitic species of Trichoderma arsenal involved in its success as BCAs as well as industrial sectors. In such instances, the integration of the translatome using ribosomal profiling and coupling it with proteomic approaches such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) for both extracellular and intracellular proteins offers a lot of scope for accurate characterization of active molecular components involved in biocontrol and then subsequently their utilization of various applications.In future, integrated efforts will help us to better understand, identify, and then explore the molecular behavior of Trichoderma–plant–plant pathogens in three way interaction will play vital role in accurate characterization of transcripts responsible for cosmopolitan nature of Trichoderma and then targeting the promising one for agricultural based applications. The latest advancements and complete genome sequencing have already provided a platform of gene pool. Further integration with latest functional techniques such as translatome will lead another step close to identification of targets in the form of active transcripts involved in a complex interaction of plant–BCA–plant pathogens.A comparative multiomic coupled insights of VS and RS prepared the manuscript. PS and AG edited the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There are limited longitudinal data regarding nutritional intake and status, and physical function in community-dwelling ethnically diverse older adults. This study explored these variables and their relationship at baseline (n=100) and after 8-months (n=81) among community-dwelling ethnically diverse older adults (≥60 years) in Birmingham, United Kingdom. Multiple pass 24-hour dietary recalls and the Mini Nutritional Assessment-Short Form assessed nutritional intake and status, respectively. The Short Physical Performance Battery(SPPB) and handgrip strength measured physical function. Linear and multinomial regression analyses were used to predict the relationship between nutritional intake, status and physical function. Mean(SD) age was 70(8.1) years , with 62% of the sample being obese. Significant decreases in intakes of vitamin B6; vitamin B1; iron; folate; and magnesium occurred over time. At both timepoints, across sexes, daily intakes of all micronutrients except vitamin B12, phosphorus and manganese were below the Recommended Nutrient Intakes. There were significant declines in SPPB scores and nutritional status over time. At baseline, younger age, better nutritional status, and higher vitamin D and fibre intakes were associated with higher SPPB scores. At follow-up, higher baseline SPPB scores  were associated with reduced decline in nutritional status. The observed declines in nutritional status and physical function, and the inadequate nutrient intakes in the absence of weight loss within eight months pose serious challenges to healthy ageing. There is an urgent need to re-evaluate and tailor appropriate dietary advice for this population to support them to age healthily.


Subgroup analysis and meta-regression were used to explore heterogeneity. A total of 65 eligible studies reported one-year prevalence estimates for 61,800 health care professionals from 30 countries. The pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 19.33% : 16.49–22.53%) and the overall heterogeneity was high across studies. We noted geographic and staff categories variations for prevalence estimates through subgroup analysis. The meta-regression showed that sample size, type of health care setting, and quality score were significant moderators for heterogeneity. One in five health care professionals experienced workplace physical violence perpetrated by patients or visitors worldwide annually. Practical intervention was needed to ensure safety of health care professionals.Workplace physical violence against health care professionals perpetrated by patients and visitors has been a persistent problem worldwide. Prevalence estimates varied vastly across studies and there was a lack of quantitative syntheses of prevalence studies. This review aimed to quantify pooled one-year prevalence estimates at the global and regional levels. A systematic literature search was performed in the databases of PubMed, PsycINFO, Web of Science, and Embase between 1 January 2000 and 8 October 2018. Studies providing information about one-year prevalence of self-reported workplace physical violence against health care professionals perpetrated by patients or visitors were included. Heterogeneity between studies was evaluated using Cochran’s chi-squared test (Cochran’s Q) and I Workplace physical violence against health care professionals has been a persistent problem of health care environment worldwide ,2. HealtThe WHO had classified workplace violence into physical violence and psychological violence. Physical violence was defined as physical force  against a person or groups that results in physical, sexual, or psychological harm . PhysicaIn order to obtain relatively reliable pooled prevalence estimates, the research included in meta-analysis should be relatively consistent in definition. The definition of workplace physical violence was more consistent across studies ,14,15. ETo address the need for global estimates of prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors, we did a meta-analysis of relevant studies around the world. We also aimed to understand how the methodological characteristics  and contextual factors  influenced the variations in prevalence estimates. A systematic literature search was performed. Possible relevant studies were screened based on strict eligibility criteria. Quality of eligible studies was assessed. Quantitative synthesized one-year prevalence of workplace physical violence against health care professionals perpetrated by patients and visitors was obtained by the meta-analysis.This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines see . The folStudies were independently screened by two reviewers (Y.-L.L. and R.-Q.L.) using the eligibility criteria described below. Studies were included if they meet the following criteria: (i) provided one-year prevalence of self-reported workplace physical violence against health care professionals perpetrated by patients or visitors; or (ii) reported definition and measurement of workplace physical violence. We excluded studies if they met the following criteria: (i) included medical student, cleaning staff, clerk, security, or administrative staff as participants; (ii) did not report perpetrators of the workplace physical violence; (iii) reported response rate <20%, or no response rate was reported; or (iv) was conference abstract, report, review, meta-analysis, letters, pilot study, protocol, or qualitative study. Workplace physical violence against health care professionals included beating, kicking, slapping, stabbing, shooting, pushing, biting, and pinching against health care professionals in their workplace . We inclTwo researchers (Y.-L.L. and R.-Q.L.) independently extracted relevant data from eligible studies and a third researcher (D.Q.) cross checked for accuracy. The following data were extracted: author, year of publication, country of study, sample size, categories of health care professionals, sampling method, method of data collection, response rate, type of health care setting, region of health care setting, and one-year prevalence estimates of workplace physical violence perpetrated by patients or visitors.The methodological quality was assessed using the eight-item Loney criteria see . Studies2 values. The significant heterogeneity between studies was assumed when p < 0.1 or I2 > 50% [Statistical analyses were performed using the “meta” and “metafor” package of R version 3·5·2 . Firstly, a normality test for the original study rates was performed to decide whether to transform the original rates. According to the normality testing results, a logit transformation method was used in this meta-analysis. Heterogeneity between studies was evaluated using Cochran’s chi-squared test (Cochran’s Q) and II2 > 50% . A randop < 0.05) in the regression model based on the result of the univariate analysis.To further explore the relevant factors influencing prevalence estimates, univariate meta-regression analysis was conducted including the following covariates: year of publication, income classification, sample size, response rate, method of data collection, professional group, region of health care setting, type of health care setting, and quality score. The multivariate meta-regression analysis included only significant variables ; reviews and conference abstracts (n = 136); used qualitative method only (n = 14); did not report definition or measurement (n = 26); had a response rate <20% or did not report response rate (n = 16); did not provide workplace physical violence prevalence data (n = 84); did not reported perpetrators (n = 89); including medical student, cleaning staff, clerk, security, and administrative staff (n = 38); and no reported and/or not one-year prevalence period (n = 71). Finally, 65 eligible studies were included for the meta-analysis .A total of 65 studies reported one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors, with prevalence estimates ranging from 2.75% to 88.31%. The lowest one-year prevalence was found among nurses in Thailand  and the For the regional level, pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 26.38% (95% CI: 18.42–36.25%) in the European region, 23.61% (95% CI: 15.25–34.67%) in the Americas region, 20.71% (95% CI: 8.59–42.07%) in the African region, 17.07% (95% CI: 13.15–21.86%) in the eastern Mediterranean region, 14.53% (95% CI: 10.05–20.54%) in the Western Pacific region, and 5.62% (95% CI: 1.38–20.14%) in the Southeast Asia region. The pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors in high-income, upper-middle-income, lower-middle-income, and low-income countries was 21.66% (95% CI: 17.49–26.51%), 19.98% (95% CI: 14.61–26.69%), 13.75% (95% CI: 9.49–19.50%), and 13.14% (95% CI: 9.62–%17.70%), respectively.Q = 4.38, p = 0.0364). Studies conducted in rural and township areas had significantly lower prevalence estimates than urban areas . The pooled one-year prevalence of workplace physical violence against male health care professionals perpetrated by patients or visitors was similar to that against female health care professionals .Prevalence estimates varied by health care facilities and staff categories. The pooled one-year prevalence estimates in tertiary hospital, secondary hospital, primary care facilities, and nursing home were 22.48% (95% CI: 15.35–31.69%), 18.83% (95% CI: 9.94–32.77%), 6.51% (95% CI: 4.36–9.64%), and 30.33% (95% CI: 22.32–39.75%), respectively. The pooled one-year prevalence of workplace physical violence against nurses perpetrated by patients or visitors was significantly higher than that against physicians . When compared studies with response rate >50%, studies with response rate ≤50% had higher prevalence estimates . Subgroup analysis showed the sampling method, year of publication, and method for data collection were not statistically associated with prevalence estimates. All details about the subgroup analysis are provided in Some methodological characteristics also influenced prevalence estimates across studies. When compared studies with sample size >500, studies with sample sizes ≤500 had higher prevalence estimates , in tertiary hospital , and lower quality score . Specifically, sample size accounted for 8.72% of the heterogeneity, type of the health care setting accounted for 14.20% of the heterogeneity, and quality score accounted for 5·41% of the heterogeneity across studies. Finally, sample size, type of health care setting, and quality score were entered into multivariate meta-regression model. Of the multivariate model, type of health care setting  and quality score  remained significant and accounted for 24.87% of the heterogeneity  to 19.77% (95% CI: 16.87–23.03%), and the Ig 0.1012 .Using meta-analytical methods, we pooled the one-year prevalence estimates of workplace physical violence against health care professionals perpetrated by patients or visitors reported in 65 studies published between 2000 and 2018. Eligible studies included 61,800 health care professionals from 30 countries. The one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 19.33% (95% CI: 16.49–22.53%) worldwide, or about one in five health care professionals annually. To the best of our knowledge, this study provided the first quantitative estimate of the prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors worldwide.Few review articles specifically focused on the prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors. A systematic review conducted in 2008 found that, on average, 25% of health care professionals have experienced workplace physical violence perpetrated by patients or visitors in general hospital . AnotherAmong eligible studies, more than half of the studies were published after 2010. We found that the year of publication was not associated with the prevalence estimates. Administrative strategies, preventive interventions, and policy against workplace violence have been advocated in health sectors over the decade ,84. A suThe results revealed that studies with sample sizes ≤ 500 and studies with low response rate had significantly higher one-year prevalence estimates. The studies’ characteristics obviously influenced prevalence estimates of workplace physical. Studies with fewer participants generally yielded more extreme prevalence estimates , which mThe result of the subgroup analysis suggested that nurses experienced more workplace physical violence perpetrated by patients or visitors than physicians. This phenomenon was supported by numerous epidemiological studies ,69,87,88Gender difference was not observed in this meta-analysis. In a systematic review emphasizing gender difference of physical violence, the researcher found that numerous studies showed male health care professionals experienced more workplace physical violence than females . This sySubgroup analyses revealed that health care professionals working in nursing homes experienced more physical violence from patients or visitors than those in other health care settings. Patients with dementia or disability in nursing homes might present more aggressive behavior and physical violence against health care professionals than general patients . Except Health care professionals working in rural or township areas experienced less workplace physical violence perpetrated by patients or visitors than those in urban areas. Few studies had emphasized the disparity between urban and rural areas . PatientThere were several limitations in the present study. First, although our study included relevant studies across 30 countries, half of the eligible studies were from high-income countries. Prevalence studies were scarce for many countries, especially for lower-middle-income and low-income countries. Considering the inconsistency of the health care environment and working conditions across the world, more prevalence studies in low-income and lower-middle-income countries are needed to understand the panorama of workplace physical violence against health care professionals. Second, the ability to compare findings and understand the magnitude of pooled prevalence was severely hampered by inconsistent methodology between studies, including inconsistent definitions, response rate, and methods of data collection. Although we have excluded those studies without description of definition and measurement, inconsistency was still inescapable. Numerous studies adopted self-designed and self-administrated questionnaire to measure workplace physical violence. It is hard to compare findings without a standard assessment tool. Thus, future research should develop a standard and comprehensive used assessment tool to measure workplace physical violence.The pooled one-year prevalence of workplace physical violence against health care professionals perpetrated by patients or visitors was 19.33% (95% CI: 16.49–22.53%). About one in five health care professionals experienced workplace physical violence perpetrated by patients or visitors annually. One-year prevalence estimates varied significantly regarding the country of study, sample size, response rate, professional group, region of health care setting, and type of health care setting. Significant moderators for heterogeneity included sample size, type of health care setting, and quality score. Future research can benefit from exploring gender differences, occupational differences, and time trends in workplace physical violence against health care professionals. More practical intervention and policy defensed workplace physical violence were needed to ensure the safety of health care professionals.


Understanding how engagement in mobile health  weight loss interventions relates to weight change may help develop effective intervention strategies.This study aims to examine the (1) patterns of participant engagement overall and with key intervention components within each intervention arm in the Cell Phone Intervention For You (CITY) trial; (2) associations of engagement with weight change; and (3) participant characteristics related to engagement.The CITY trial tested two 24-month weight loss interventions. One was delivered with a smartphone app (cell phone) containing 24 components  and included prompting by the app in predetermined frequency and forms. The other was delivered by a coach via monthly calls  supplemented with limited app components  and without any prompting by the app. Engagement was assessed by calculating the percentage of days each app component was used and the frequency of use. Engagement was also examined across 4 weight change categories: gained (≥2%), stable (±2%), mild loss (≥2% to <5%), and greater loss (≥5%).r=−.213; personal coaching: r=−.319), number of apps use per day , and percentage of days self-weighed . None of the characteristics examined, including age, gender, race, education, income, energy expenditure, diet quality, and hypertension status, appeared to be related to engagement.Data from 122 cell phone and 120 personal coaching participants were analyzed. Use of the app was the highest during month 1 for both arms; thereafter, use dropped substantially and continuously until the study end. During the first 6 months, the mean percentage of days that any app component was used was higher for the cell phone arm  than for the personal coaching arm . The cell phone arm used the apps an average of 5.3 times/day (SD 3.1), whereas the personal coaching participants used them 1.7 times/day (SD 1.2). Similarly, the former self-weighed more than the latter . Furthermore, the percentage of days any app component was used, number of app uses per day, and percentage of days self-weighed all showed significant differences across the 4 weight categories for both arms. Pearson correlation showed a negative association between weight change and the percentage of days any app component was used  Mobile health  technology provides innovative ways to create interventions that may help people lose weight and sustain weight loss -3. mHealThe effectiveness of behavioral weight loss studies that are delivered in person is known to be moderated by dose . AlthougIn this report, we defined engagement specifically as interaction with components of the intervention and then assessed various types of engagement to understand how and whether engagement relates to weight management. Specifically, we defined engagement as the frequency of use of various intervention components of the cell phone app and the attendance of the in-person group sessions and phone counseling calls. We theorized that a higher engagement may reflect individual motivation and lead to a greater commitment for behavioral change and, thus, a higher intervention efficacy in the Cell Phone Intervention For You (CITY) clinical trial.P<.01). There was also a large variability in weight loss within each arm—some participants lost a substantial amount of weight, whereas others did not. The CITY intervention provides an opportunity to examine engagement because it incorporated various strategies for delivering intervention components, such as using sensor technology for capturing data from a wireless scale, providing tailored feedback, and using prompting as a reminder strategy. In addition, detailed and careful collection of both engagement data and weight data allows for examination of the association between engagement and weight and for examination of factors that may influence engagement. Thus, this work examines (1) the patterns of participant engagement overall, and with key intervention components within each intervention arm, in the CITY trial; (2) the associations of engagement patterns with weight change; and (3) the participant characteristics related to intervention engagement.In the CITY trial, we compared 2 behavioral interventions for weight loss: the cell phone (CP) intervention arm and the personal coaching (PC) arm . Even thThe CITY study was 1 of the 7 trials in the Early Adult Reduction of weight through LifestYle Intervention consortium, sponsored by National Heart Lung and Blood Institute  . Th. Th10]. use of each app component to be achieved when a participant completed an important, but also measurable, interaction with that component. In other words, looking at a screen that asks a participant to take a weight reading does not count as use, but entering a weight value when asked to do so does count as use. Engagement data were summarized for each participant for each app component for each day; then, the participant-level data were averaged for the CP and PC arms (separately and combined) over time by month and by 3 specific intervention periods: from baseline to 6 months, 7 to 12 months, and 13 to 24 months. These periods correspond to distinct phases of the intervention with regard to availability and frequency of different app components.Recognizing that engagement with different components of the intervention demands different amounts of time and effort , we evaluated all components of engagement combined and separately for specific app components. For this manuscript, we considered a discrete instance of We also examined the relationship between categories of weight change and engagement during the 3 study periods. Weight change was grouped into 4 categories: gained (≥2%), stable (±2%), mild loss (lost ≥2% to <5%), and greater loss (lost ≥5%). These categories were chosen to reflect current guidelines that support 2% to 5% weight loss as clinically meaningful and stable weight as within ±2% of weight gain or loss . One-wayP value of <.05 was considered statistically significant. All analyses were conducted using SAS 9.4 .To understand whether baseline characteristics were associated with higher levels of engagement during the first 6 months of the intervention, we examined the distribution of selected baseline characteristics across quartiles of the mean number of times any app component was used per day (including self-weighing) for the PC and CP arms separately. Baseline characteristics such as age, gender, race, ethnicity, education, income, weight, BMI, energy expenditure, healthy eating index score, and hypertension status were examined. All statistical tests were two-sided, and a 2 (SD 7.9). Approximately 69.8% (169/242) of these participants were female and 37.1% (90/242) were black.Similarly, during the first 6 months, the CP arm had a higher mean percentage of days self-weighed compared with the PC arm . Within the PC arm, engagement in the face-to-face group coaching sessions was high during the first 6 months , as was engagement with monthly calls and group sessions combined .The pattern of early reduction in engagement is also observed when we examined the engagement pattern for each of the app components by intervention arm and over time. Overall, not counting the use of the CITY home screen component, the CP arm used the app components about 3.24 times a day during the first 6 months, whereas the PC arm used components about 1.08 times a day during the same timeframe (data not shown). Right Now in CITY.The second most used app component was the detailed food tracker, with a median daily mean use of 0.46 and 0.35 times per day during the first 6 months in the CP and PC arms, respectively, which is approximately every 2 to 3 days. The detailed food tracker use decreased by more than half during months 7 to 12 and further reduced to about once every 1 to 3 months during the last 12 months in both arms (months 13-24). In the CP arm, where participants were prompted daily to self-weigh, use of the self-weighing component was about every other day during months 1 to 6, which decreased slightly during months 7 to 12 and further reduced to about once every 4 to 5 days during months 13 to 24. For the PC arm participants who did not receive prompting from the smartphone but were encouraged by their coach during monthly calls, the self-weighing component was used about once every 4 days during months 1 to 6 and dropped to about once every 8 days during months 7 to 12 and once every 12 days during months 13 to 24. The CP participants used other components of the app every 2 to 20 days during months 1 to 6, and the use reduced to almost none for the rest of the study. These other components consisted of the sugar-sweetened beverage tracker, physical activity tracker, veggie tracker, meat tracker, goal setter, fruit tracker, and a screen with updates titled Other than the detailed food tracker and self-weighing, the PC participants rarely used any of the rest of the app components that were available to them during the entire study.r=−.213, PC: r=−.319), the mean number of times app was used per day , or the mean percentage of days participants self-weighed  were each correlated with weight change during the first 6 months.We also examined selected baseline characteristics of mean number of times the app was used per day during the first 6 months in CP and PC arms separately, across the 4 quartiles. None of the characteristics examined appeared to be related to the varying engagement patterns of the participants see  and 3.Our results demonstrate that engagement in mHealth delivery of a behavioral weight loss intervention was associated with weight loss. Our findings suggest that the more the participants used the smartphone app or self-weighed, the more weight loss was observed during the first 6 months of the study for both intervention arms. This association continued to be true for the PC arm into months 7 to 12, but not for the CP arm. Despite the fundamental differences in the time and effort needed in using various components of the smartphone app or in completing personal contacts , the finding is consistent—engagement with the intervention is associated with weight loss. It is unclear, however, what level of engagement is required for effective weight loss, and if a different level of engagement is effective for weight loss maintenance.Our findings are consistent with previous research showing that greater engagement with an intervention was associated with greater weight loss, even with different types of engagement measures -19. For Unlike self-weighing, other components of self-monitoring components such as dietary tracking were only used during the first month and almost never used beyond the first month. This low engagement in dietary tracking may result from low motivation ,26 or diIndeed, ours and other studies have shown that the engagement dropped drastically, even after the first month, and declined continuously over time ,28-30. IIn a 12-month behavioral weight loss study, the self-monitoring pattern of 148 participants also varied and declined over time . Indeed,Although traditional personal contact has been perceived as the ideal mode of intervention delivery, in this study, completion of the group sessions alone or combined with monthly calls in the PC arm was not significantly associated with weight change. However, engagement as assessed by overall app use or self-weighing was significantly associated with weight loss, even for the PC arm that received regular and sustained personal support. This finding suggests that mHealth for behavioral interventions could supplement and even enhance interventions based on personal contact, even in the setting of a reduced engagement pattern. Combining mHealth intervention with human support may be more efficient than using either of them alone. This is consistent with a recent study that randomized 102 participants into 3 weight loss intervention arms versus control for 12 weeks: a personal contact arm, an mHealth app-only arm, and a combined arm with personal contact and an mHealth app. The authors reported that the combined personal contact and mHealth app arm was as effective as the personal contact arm and tended to be more effective than the mHealth app arm . Thus, fOur data suggest that prompting may be helpful to generate engagement to some degree because the CP arm that received prompting regularly used the smartphone app components more than the PC arm did across all measures of engagement. A meta-analysis of 14 studies with varying designs showed that technology-based prompting had a small to moderate effect on engagement as compared with no-strategy . ParticiThis study has several strengths. The engagement data reported here were collected objectively with a smartphone app, and the main outcome of weight was reliably measured at each of the study visits in the clinic and does not rely on self-reporting. Furthermore, this study generated a relatively large amount of engagement data of young adults (n=242) for an extended period (24 months). Another strength of this study is the ability to collect engagement data with each of the cell phone app’s components and with the personal interactions, where the design of the intervention components was based on behavioral theories and prior research evidence.The study has several limitations that must be considered when interpreting data. Regardless of the reason for joining the CITY study, the varying motivation for weight loss among the participants may have contributed to the varying level of engagement in the intervention arms. Increasing motivation may increase engagement and subsequent weight loss; however, identifying effective level of engagement may also be important for all weight loss studies and programs. Another weakness of the study is that limited study resources prevented development of an intervention app as attractive, polished, and robust as some commercial apps, which could have an impact on engagement. Unfortunately, it was beyond the scope of this study to tease apart whether the reduction in engagement over time may have been due to lack of motivation or challenges with the app design and other technical reasons. Our study compensation for smartphone data coverage, which was offered to both the PC and CP arms, may have incentivized participants to stay in the study but would not contribute to the differences in engagement between the 2 arms. This compensation would not be available to app users if the app were widely deployed. Our compensation, however, did not require any substantial level of engagement or use of app components, and so, participants with low motivation who may have otherwise dropped out of the study may have continued until the end. The overall engagement was lower than expected and desired, but the pattern was consistent with other studies. Messages and tips to encourage healthy lifestyle and weight loss management were delivered through the app home screen, but the smartphone’s operating system prevented the measurement of whether participants covered them up with other app icons or even turned off the messages altogether; this behavior would affect engagement. The fact that engagement dropped substantially early suggests that a more effective intervention that automatically adapts to behavior and self-measured engagement, such as using just-in-time adaptive design, may be needed ,36. AnotIn this study, engagement assessed using different measures was associated with weight loss. Nevertheless, engagement declined over time at varying rates for different intervention engagement components. This study suggests that a variety of strategies may be needed during different stages of an intervention to increase and sustain engagement required for intervention effectiveness. Self-weighing was associated with weight loss regardless of the baseline characteristics of the participants, suggesting that an effective weight loss program may not need to include multiple behavioral strategies. Focusing on a single effective strategy in conjunction with prompting may be better than offering more components that most participants may not use. Future studies should clarify the definition of effective engagement. In addition, future studies should explore the motivations for participant engagement and nonengagement to design effective strategies for addressing those specific challenges.