Preterm birth increases the risk for postpartum depression in both mothers and fathers, calling for strategies to alleviate and prevent depressive symptoms in parents of preterm infants. The aim of this study was to assess the association between early parent-infant closeness and later depressive symptoms among parents of preterm infants. We hypothesized that longer duration of closeness associate with fewer depressive symptoms in both parents.This prospective cohort study included 23 neonatal intensive care units (NICUs) from 15 countries in 2018 to 2020. Each unit recruited families with preterm infants aiming to 30 families. The total duration of parents’ presence in the NICU, and separately parent-infant skin-to-skin contact and holding, were measured using a Closeness Diary up to 14  days. The Edinburgh Postnatal Depression Scale (EPDS) was used at discharge and at 4  months corrected age of the infant.The study included 684 mothers and 574 fathers. The median presence was 469   min  per 24   h for the mothers and 259   min (Q1 100 and Q3 540) for the fathers; mean EPDS scores were 9.2 (SD 5.0) and 6.3 (SD 4.4) at discharge and 6.6 (4.7) and 4.3 (4.2) at 4  months, respectively. Parents’ presence and depressive symptoms varied greatly between the units. Parents’ presence as the total measure, or skin-to-skin contact and holding separately, did not associate with depressive symptoms in either mothers or fathers at either time point (adjusted).No association was found between the duration of parent-infant closeness in the neonatal unit and parents’ depressive symptoms. The beneficial effects of family-centered care on parents’ depression seem to be mediated by other elements than parent-infant physical closeness. More research is needed to identify the critical elements which are needed to alleviate parents’ depression after NICU stay. Preterm birth implies several consequences, such as a risk for abnormal child development and compromised parental wellbeing, including a risk for depression . MaternaToday, parent-infant closeness, as opposed to separation, is recognized as a key issue in the neonatal intensive care setting when implementing infant- and family-centered care supporting later infant and family health. Closeness can be described both in terms of physical closeness, ranging from the parents’ presence in the unit to being in direct skin-to-skin contact with the infant, as well as in terms of emotional closeness, experiencing feelings of love and affection . A wide There are a number of potential pathways through which physical closeness may affect postpartum depressive symptoms in the parents of preterm infants. The postpartum period is a sensitive period for both mothers and fathers to develop a loving bond to their infant, strongly regulated by oxytocin hormone and its effects in the limbic network of the brain, the center for reward and emotionality . Skin-toA systematic review and meta-analysis  showed sCurrently, we do not have knowledge about how different types of early parent-infant closeness influence parents’ depressive symptoms. It is noteworthy that studies including fathers are rare. Thus, the aim of this prospective study was to assess the association between early parent-infant physical closeness and later depressive symptoms among both mothers and fathers in a large international group of NICUs. We hypothesized that a longer duration of parents’ presence, especially skin-to-skin contact and holding, would associate with fewer depressive symptoms in parents.This study question was one of the two main aims of the 2nd International Closeness Survey. The other aim was to study the association between the quality of family-centered care in the units and later parental depression . STROBE The families were invited to participate in the study if their infant was born below 35 weeks of gestation, admitted in the participating NICU, and the family had a mobile phone for data collection for another arm of this study. The exclusion criteria included: (1) the infant’s estimated hospital stay length being less than 3 days, (2) any life-threatening medical condition of the infant, (3) triplets, and (4) parents who were unable to read English or the local language at the study site. Recruitment took place as soon as appropriate before the sixth day of life, except for 2 units where the local ethics committee did not permit recruitment until the second week of life. The study units kept a record of all admissions of infants below 35 gestational weeks in order to evaluate the representativeness of the study participants. The data included the infants’ gestational age, birthweight, length of hospital stay, and the distance from home to hospital (as driving time) as well as the reasons of ineligibility if present.A Closeness Diary  was usedThe Edinburgh Postnatal Depression Scale EPDS;  was usedThe association between the amount of parent-infant closeness  and parent depressive symptoms was assessed using separate linear mixed models for repeated measures with units as random effects applying compound symmetry covariance structure. The depression scores were square root transformed prior to analysis, as this was necessary in order to meet the residual normality requirement in such models.All analyses were adjusted for the infants’ gestational age, multiple status (singleton/twin), maternal education , relationship status (single/living in relationship), and sibling status (older siblings present/no siblings). Also the closeness x time interactions and the interactions of the confounders with time were included in order to allow for different degrees of association at discharge and at 4 months corrected age.p below 0.05 were considered statistically significant.The analyses were carried out using SAS for Windows version 9.4 . Values of The study was approved by the Ethics Committee of the Hospital District of Southwest Finland as well as by the scientific research committee of the Pediatric Department of the Turku University Hospital, Finland (T08/011/18). In addition, each study site sought approval from their local research ethics board and/or hospital as required. Data collection began at each site after local approval was obtained. Eligible parents were given oral and written information about the study procedures, and those who agreed to participate provided written informed consent. Study questionnaires and documents were identified with an identification code to conceal the participants’ identities. The electronic platform REDCap used in this study required passwords for access.The study participants included 684 mothers and 574 fathers. The flowchart  shows thThe mothers were present for a mean of 658 (SD 463) minutes, holding the baby for 72 (121) minutes and in skin-to-skin contact with the baby for 106 (122) minutes per day during the diary days; the fathers were present for 427 (383) minutes, holding the baby for 23 (42) minutes and in skin-to-skin contact with the baby for 74 (92) minutes per day. The data is shown on the unit level in The mothers’ pooled mean EPDS score was 9.2 (SD 5.0) at discharge and 6.6 (4.7) at 4 months after the due date. Between the units, their EPDS mean score varied from 5.8 to 12.5 at discharge and 4.7 to 9.6 at 4 months. A total of 25.3% of the mothers exceeded the EPDS threshold at discharge and 12.3% after 4 months. The proportion of mothers exceeding the screening threshold (13 or more) varied from 0 to 53.3% at discharge and 0 to 27.3% at 4 months after the due date between the units.The duration of the mothers’ presence, holding or skin-to-skin contact did not associate with either the mean EPDS score or the proportion of mothers exceeding the screening threshold at either time point when adjusted for the potential confounders. The results remained unchanged in a post-hoc analysis with a lower threshold of 10. The Pearson correlation coefficients are shown in The fathers’ pooled mean EPDS score was 6.3 (SD 4.4) at discharge and 4.3 (4.2) at 4 months. Their EPDS mean score varied from 3.3 to 7.9 at discharge and 1.6 to 7.5 at 4 months between the units (excluding two centers in which only one father responded at both time points). A total of 8.3% of the fathers exceeded the EPDS threshold at discharge and 5.8% after 4 months. The proportion of fathers exceeding the screening threshold (10 or more) varied from 0 to 23.1% at discharge and 0 to 20.0% at 4 months between the units.The duration of the fathers’ presence, holding or skin-to-skin contact did not associate with either the mean EPDS score or the proportion of fathers exceeding the screening threshold at either time point when adjusted for the potential confounders.This large prospective study about parent-infant closeness and parental depression included parents of preterm infants in 15 countries. It found no association between the duration of parents’ presence in the NICU during the first weeks of hospitalization and their later depressive symptoms, neither did the duration of holding or skin-to-skin contact associate with depressive symptoms in mothers or fathers.We focused on physical closeness between parents and preterm infants in the beginning of their hospital stay, paying attention to the duration of early contact at different degrees of proximity. Although this two-week period covered only a fraction of the whole hospital time for the most immature infants, this timeframe was chosen as it can be argued that the early postpartum period is an important time period for forming a bond between the parent and the infant. This is also a time period in an NICU context that traditionally involves disruption of parent-infant closeness as well as acute parental distress .Depression was measured twice. Measurements at discharge are commonly used, and the differences in early parent-infant closeness could already have made a difference. The second time point was chosen to evaluate prolonged depression with a stronger clinical significance . The levParenting interventions in the NICU have been shown to have various effects on parental depressive symptoms. Some of them have decreased maternal depression , while oDepressive symptoms among the parents of preterm infants varied between the units despite using the same methods, cut-offs, and age points. Depressive symptoms associated with the quality of family-centered care reported by the parents . This vaThe strengths of this study included the large number of participating NICUs, providing us with a large variation in physical closeness. The prospective data collection provided us with detailed, day-to-day data. The data collection tool, Parent-Infant Closeness Diary, has been shown to be a reliable and feasible tool when collecting data on physical parent-infant closeness for up to a 2-week period .There are limitations in this study. Although a vast majority of eligible families participated in this study, it is likely that those with little presence at the hospital were not approached and that those with more depressive symptoms declined participation. Yet, our study included a large variation of parental presence and depressive symptoms and provided us with a representative group of families in the NICU. Due to the unpredictable nature of preterm birth, depression could not be screened for during the prenatal period and, therefore, we have not been able to control for prior depression in our cohort. Furthermore, even if the EPDS is a validated tool with recommended cut-off points for postpartum depression in both mother and fathers, there are cultural differences in the expression of depressive symptoms leading to heterogeneity in sensitivity and specificity for detecting different levels of postnatal depression across different cultural settings . For theIn conclusion, our results did not confirm the hypothesis that the duration of parents’ presence in the NICU during the first weeks of hospital care has a major role in the prevention of parental depressive symptoms. Our results suggest that care culture should be studied broadly including several elements of family-centered care to understand the mechanisms behind the variable levels of depressive symptoms among parents in different units.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Committee of the Hospital District of Southwest Finland as well as by the Scientific Research Committee of the Pediatric Department of the Turku University Hospital, Finland (T08/011/18). In addition, each study site sought approval from their local research ethics board and/or hospital as required. The patients/participants provided their written informed consent to participate in this study.LL and AA conceptualized and designed the study and drafted the initial manuscript together with SLi. BP did the statistical analyses. All authors participated in the data collection and reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


As a sequela of the COVID-19 pandemic, a large cohort of critical illness survivors have had to recover in the context of ongoing societal restrictions.We aimed to use smartwatches  to assess changes in the step counts and heart rates of critical care survivors following hospital admission with COVID-19, use these devices within a remote multidisciplinary team (MDT) setting to support patient recovery, and report on our experiences with this.We conducted a prospective, multicenter observational trial in 8 UK critical care units. A total of 50 participants with moderate or severe lung injury resulting from confirmed COVID-19 were recruited at discharge from critical care and given a smartwatch (Fitbit Charge 3) between April and June 2020. The data collected included step counts and daily resting heart rates. A subgroup of the overall cohort at one site—the MDT site (n=19)—had their smartwatch data used to inform a regular MDT meeting. A patient feedback questionnaire and direct feedback from the MDT were used to report our experience. Participants who did not upload smartwatch data were excluded from analysis.P=.003). The mean resting heart rate decreased from 79 (SD 7) beats per minute in the first month to 69 (SD 4) beats per minute at 1 year following discharge (P<.001). The MDT subgroup’s mean step count increased more than that of the control group  over 1 year. Further, 71% (10/14) of smartwatch users at the MDT site and 48% (10/21) of those at the control sites strongly agreed that their Fitbit motivated them to recover, and 86% (12/14) and 48% (10/21), respectively, strongly agreed that they aimed to increase their activity levels over time.Of the 50 participants recruited, 35 (70%) used and uploaded data from their smartwatch during the 1-year period. At the MDT site, 74% (14/19) of smartwatch users uploaded smartwatch data, whereas 68% (21/31) of smartwatch users at the control sites uploaded smartwatch data. For the overall cohort, we recorded an increase in mean step count from 4359 (SD 3488) steps per day in the first month following discharge to 7914 (SD 4146) steps per day at 1 year (This is the first study to use smartwatch data to report on the 1-year recovery of patients who survived a COVID-19 critical illness. This is also the first study to report on smartwatch use within a post–critical care MDT. Future work could explore the role of smartwatches as part of a randomized controlled trial to assess clinical and economic effectiveness.RR2-10.12968/ijtr.2020.0102  Worldwide, the COVID-19 pandemic has resulted in a large cohort of patients presenting to critical care units with acute lung injury requiring protracted ventilatory support. In the United Kingdom alone, from March 2020 to the time of writing, a total of 44,898 patients with confirmed COVID-19 have been admitted to critical care [The patients admitted to intensive care were typically male, were aged over 70 years , and speTo date, there is a lack of detailed, long-term outcome data for survivors of COVID-19 critical illness. Furthermore, rehabilitation has been challenged by social distancing, the attenuated availability of health care services, the isolation of survivors from their social support groups, restricted interventions involving face-to-face treatment, and the closure of rehabilitation settings in the community.Smartwatch use has been rapidly growing, especially over the last 5 years . SmartwaThis study aimed to (1) use smartwatches  to monitor changes in the step counts and heart rates of a cohort of participants who survived an admission to critical care during the first wave of the COVID-19 pandemic (April to June 2020) and (2) explore the use of these devices within a rehabilitation setting and report on our experiences with this.Ethical approval was granted by Health Research Authority and Health and Care Research Wales (Yorkshire & The Humber – Bradford Leeds Research Ethics Committee reference number: 20/YH/0157 IRAS 280041).We conducted a prospective, multicenter observational trial in UK critical care units. The original protocol for this study was published previously .A total of 50 participants were recruited from 8 UK hospitals in South East England . Adult pAt each site, participants were approached at or shortly after discharge from higher dependency care between April and June 2020. Participants were recruited by a physiotherapist or critical care physician. Each site had a local research team for recruiting participants and setting up the smartwatches. Participants were assigned an anonymized study reference ID number, which was used for all data collection procedures. Demographic data were collected for each participant. For the purposes of sample characterization, further data were collected regarding the comorbidities and treatments received during participants’ critical care admission .Fitbit Charge 3 watches were given to each patient and linked to their anonymized study reference ID numbers. Data were synced to the Fitbit app and then periodically downloaded to a central study database. Participants were asked to wear their smartwatch for as long as they felt able and to ideally aim to use the smartwatch continuously. Participants were given a contact number for a member of the research team that they could use to obtain help for using their smartwatch.The smartwatch data extracted included daily step count and daily resting heart rate in beats per minute, which was defined as the lowest mean heart rate recorded during a period of inactivity of at least 30 minutes . FurtherMDT site , usual follow-up care was provided without feedback based on the smartwatch data and without MDT intervention.One-year follow-up visits were completed by a member of the research or physiotherapy team at each site. These were primarily completed via face-to-face or telephone appointments. A patient feedback questionnaire  was compSmartwatch use was defined as participants using their watch for a minimum of 1 month. A month was included for analysis if there were over 10 days of data for that month. A data set was considered complete at 1 year if there were data for every month of the year. Patients were considered adherent if they used their smartwatch for any month and were excluded from analysis when there were no data uploaded for any month. Participants were included for comparative analysis at 1 year if data for month 1 and month 12 were present.All data were analyzed using R , and raw data were collected in Microsoft Excel.P values were calculated to determine statistical significance, and actual values were included in analyses unless P was <.001. Data were tested for normality via Shapiro-Wilk testing, and significance was tested by using a 2-tailed Student t test.Feedback based on patients’ experiences with the recovery from critical illness was incorporated via patient research champions to inform the design of this study. The COVID-OR (Coronavirus Disease-Observation of Recovery) study steering group had 2 previous patients on the panel that helped to tailor this study to patients’ preferences, and the steering group will help disseminate the results via a patient network of critical care survivors.The participants who were recruited across sites in South East England totaled 50. The smartwatch users who were included for analysis totaled 35 participants .P=.22), comorbidities (P=.35), and the length of critical care stay (P=.37) or hospital stay (P=.46) between the MDT and control groups. Similarly, there were no statistically significant demographic differences between smartwatch users (n=35) and nonusers  years , 74% . Participants had increased their mean step count by 37%  from 0 to 3 months following discharge. At 12 months, the mean step count increased by 82%  when compared with that for month 0.The full cohort had an average of 4359 (SD 3488) steps per day in the first month following discharge. At 1 year, this had increased to an average of 7914 (SD 4146) steps per day (P=.04) over 1 year. However, the MDT group was less active than the control site group in the first month (3107 steps vs 5133 steps), and increases were similar between the two groups until month 12  at 3 months after data collection and a total reduction in mean heart rate of 13% (−10 beats/minute) by 12 months .Heart rates averaged 79 (SD 7) beats per minute in the first month following discharge and 69 (SD 4) beats per minute at 1 year following discharge for the full cohort. Participants had a reduction in mean heart rate of 7%  of smartwatch users agreed or strongly agreed that their smartwatch was easy to use, 80% (28/35) felt that smartwatches helped them and motivated them to recover, and 83% (29/35) aimed to increase their activity level over time . ParticiIn the cohort whose smartwatch data were used to inform the rehabilitation MDT, a sudden reduction in step count among 3 separate participants raised a concern that could be addressed by the MDT. These participants initially received a telephone call to enquire about this reduction in step count. They were then referred to specialist services as required. This prompted the rapid recognition of specific patient problems prior to the patients self-reporting the problem to a clinician. Examples of such problems include acute joint inflammation and myocardial ischemia. Further feedback from the MDT members suggested that participants in the MDT subgroup felt supported and reassured by the observations of the clinical team, and this positively improved participants’ recovery.The adherence rates for smartwatch use were 70% (35/50) in the overall cohort, 74% (14/19) in the MDT group, and 68% (21/31) at the control site . Of the This multicenter study demonstrated that smartwatches can be used to observe a significant increase in participants’ daily step counts over a 12-month recovery period from COVID-19–induced critical illness. This study also provides information on the use of a remote critical care rehabilitation MDT that used smartwatch data to support patient recovery. Smartwatches were perceived to be user-friendly, were well tolerated, and added value by providing rapid feedback to the MDT. On 3 occasions, the smartwatch data provided actionable data to the MDT that triggered referrals to other specialties.Participants were discharged from hospitals after critical care admissions and significant deconditioning, and step counts were well below those of active adults  ,33 and tThis study demonstrated that smartwatches can allow monitoring of physical activity remotely, though a considerable number of participants, despite perceiving their devices to be easy to use, did not use them regularly. This presents a limitation to this study but also adds important information to critical care rehabilitation literature, and future studies might need to include a similar dropout rate when using smartwatches in a similar cohort or assessing a smartwatch intervention. Our smartwatch usage rates are broadly similar to those of previous studies ,36, thouDevice use was similar between the MDT site and control sites and suggested that some participants were not motivated to use their smartwatch despite regular reminders from a member of the MDT. The reasons for inadequate data included the infrequent use of the smartwatch; hardware failure; the failure to sync data despite participants using the watch; and lastly, participants not wearing the device at night.Although the quantitative results suggested limited differences between the MDT subgroup and control groups, the feedback from participant feedback questionnaires suggested an increased perception that the smartwatches provided motivation for recovery and for increasing activity levels over time in the MDT site group. Further, while we acknowledge that recovery is a complex phenomenon and that, similarly, an MDT is a complex intervention, these responses might provide insight into an intervention group that could be encouraged to become fitter via the use of smartwatches.Although the use of smartwatches is increasing  and the There are limited reports of 1-year outcome data for post–critical care survivors with COVID-19. However, data from 1-year outcome studies are in line with our data, and such studies have reported significant recovery from COVID-19 illness , albeit First, the resource limitations involved in recruitment during the first wave of a global pandemic resulted in little data being available regarding the number of patients who were initially approached but declined to participate in this study. Centers approached as many participants as their resources allowed, and despite our demographic data suggesting that our participant samples were representative of the critical care population at the time, the little data we have regarding the number of initially approached participants and those who declined to participate may limit the generalizability of our results.Second, in a multicenter observational study using wearable technology during a pandemic, missing data are inevitable. The management of these missing data was challenging and was carefully considered. We believe that our data, which were collected for at least 10 days in a given month, were representative of the sample, especially given the high sampling frequency (amount of data collected per minute) of the smartwatches.This study explored the use of a smartwatch-enabled MDT, and the next steps should be to robustly assess clinical effectiveness and cost-effectiveness in an adequately powered randomized controlled trial. The analysis of patients’ perceived recovery and smartwatch-assessed activity levels in a larger study would also provide further insight into the use of smartwatch devices. Overall, this smartwatch-assisted approach could lend itself to other clinical contexts where physical optimization is crucial, such as perioperative settings for those undergoing major surgery.Smartwatches can be used to observe an increase in activity among patients following hospital admission with COVID-19 critical illness. The observed trend in daily step counts was encouraging, given the severity of the illness and the level of deconditioning at hospital discharge. Though a considerable number of participants did not use their smartwatches as intended, the technology was used to support the care delivered to participants in a remote MDT setting and was able to detect significant changes in activity levels. Further work is required to assess the clinical effectiveness and cost-effectiveness of this intervention and whether it can result in improved patient outcomes and quality of life.


In study one, pigs were over 4 kg heavier 16 weeks post-weaning when the MP was present for 48 h post-weaning compared to control pigs (p = 0.05). The three other studies used a 7-days bioassay to assess the best dose and form of delivery of the MP among weaned pigs. The single measure that responded uniformly was the percentage of pigs that lost body weight in the first 7 days after weaning. Among control pigs in four separate studies, 25% of the weaned pigs in each study lost body weight by 7 days after weaning, while in 3 of the 4 bioassay studies, 0% of MP-exposed pigs lost weight after weaning (one study had 6% of pigs losing body weight with the MP). This MP effect is both highly statistically significant and, if found on commercial farms, would have a large positive economic benefit. Simultaneously, having fewer pigs losing weight and exhibiting less aggressive behavior will improve the health and welfare of weaned pigs. Providing biologically-relevant olfactory enrichment can improve pig health and welfare.The post-weaning environment in commercial pig nursery buildings is typically devoid of both the sow and her semiochemicals. Among other factors, the loss of maternal odors may contribute to post-weaning stress. In this work, we report four studies (studies 1-4) using 192 weaned pigs to evaluate the effects of a maternal pheromone (MP) containing Myristic Acid and Skatole on weaned pig behavior and performance. Study 1 examined behavior among weaned pigs with a focus on lying, aggression and feeding behaviors. All studies used body weight gain and the percentage of pigs that lost weight the first 7 days after weaning as key response variables. The MP stimulated early feeding behavior and reduced aggressive behaviors among weaned pigs ( Commercial piglets are weaned at an earlier age than their natural setting in the wild. While feral pigs generally practice gradual weaning over a period of weeks , pigletsWeaning is stressful to piglets due to the number of changes within their environment. The environment transitions from a familiarity of litter mates and maternal presence to strange odors and foreign piglets filling the post-weaning pen. The change from maternal milk to solid dry pellets can cause starvation, malnourishment, and reduced growth rate –3. The fDuring lactation, piglets nurse about 20 times a day, nearly hourly. After weaning, dry feed is presented to them usually in a continuous manner. The feed form is different (solid grain-soy rather than milk), and the behavior required to consume dry feed is different than suckling. In addition, the lack of maternal odors leads to piglet confusion and a delay in solid feed consumption.Piglets learn the odor of its mother by 12 h of life . While aA MP is an important semiochemical from a female directed toward her offspring. Some of the first research conducted with maternal pheromone was in rats in the 1980's  SynthetiThe goals of these studies were to (1) confirm that this novel MP stimulated post-weaning performance, reduced aggression, and increased feeding, and (2) develop a simple bioassay to determine the extent to which the MP can stimulate weight gain and reduce fighting when the dose and delivery methods were improved. We report a simple bioassay to test concentrations and delivery methods of MP or similar technologies. We also report in a longer-term study that tracked pig performance into the finishing phase showed potential benefits of this new concept. Small improvements in post-weaning performance can result in larger weight gain later in life.Four studies were conducted at the Texas Tech University (TTU) research farm to determine a method of application of the maternal pheromone to newly weaned piglets. One study kept pigs on study until finishing to examine the long-term effects of MP on weaned pigs. The maternal pheromone was applied to the treatment feeders in each study to identify its effects on growth, behavior, and performance.via a five-hole feeder and a single nipple drinker per pen. Room temperatures were set at about 32 C at weaning and dropped about 2 C per week to accommodate the thermal needs of the piglets. Piglets were housed four per pen with wire or plastic flooring providing 3.2 m2 of total floor space. Piglets were derived from PIC Camborough sows and PIC Duroc boars.All studies were approved by the TTU Animal Care and Use Committee prior to the start of the work (IACUC # 19104-12). Studies were conducted at the TTU swine unit which is an 80-sow farrow-to-finish operation near the TTU campus. The farm has two, 16-crate farrowing rooms and 2 nursery rooms. Each room has separate ventilation with 100% fresh air entering. Pigs were fed standard corn-soy-vitamin-mineral diets. All piglets had ad libitum access to feed Each study randomly distributed weaned piglets and blocked them by litter, sex, and weight to treatments. Piglets were weaned at 21 days of age with an average weight of about 5.5 kg (specific data reported for each study). During the studies, we had no pig deaths. The pigs were considered high health with no major infectious diseases.The pen was the experimental unit for all studies, while also controlling for litter, sex and body weight. Each study was balanced in that there was an equal number of experimental units per treatment group. Each pen contained two castrated males and two females. Pig gender does not have a large effect on pig performance or behavior at this age.A total of 192 weaned pigs were evaluated. Numbers of pigs and pens are given for each study below.General Linear Models were used to analyze and summarize the parametric data. The first model evaluated each of the three treatments, compared with the control group. When we had a control and 2 forms or doses of MP, we also performed linear contrasts to compare control with the combined MP treatments. When more than two treatments were present, the predicted different test was used to separate means in each study. All statistics were performed by SAS software  or Microsoft Excel.An experiment-wise or a meta-analyses was used to assess multiple dose and form of delivery studies to see if an overall effect of MP treatment could be assessed relative to the control group. Also, these small range-finding studies are useful to determine an adequate sample size best to use for the bioassay. At this early stage in development of this technology, mean differences in the face of large variation are difficult to find significant differences where they may be present. Therefore, for studies 2 through 4, we looked only for mean differences, not statistically significant differences.P < 0.05 mean effect with an alpha of 0.80 for a single study to be statistically significant. This information can establish both the sample size needed for future bioassays or longer-term studies.When all studies were combined, we performed a power test to estimate the sample size needed for a Rather than having people spray feeders with the MP as in our previous work, we sought ways to apply it to the feeder with minimal labor. To investigate this, we first examined two technologies: sponges and beads. Treatments included replicate pens containing either; a control (with nothing added), two sponges hung over the feeder onto which the MP was poured at times zero and 24 h post-weaning, or sodium alginate beads containing MP. We examined 4 replicate pens for each of three treatments .The second treatment can be seen in The maternal pheromone in Study 1 was diluted in 70% isopropyl and blue dye with over-the-counter food coloring. A stock solution of the MP with 10 μg concentration was diluted into 100 mL of 70% isopropyl to decrease the concentration to 1 ppm for the treatment groups. This dilution was poured directly on to the sponges or infused into the beads before applying to the feeders. A total of 1,600 mL of pheromone was used throughout Study 1.Performance (weight in kg) recordings for this study were collected at time of weaning as well as 7 days, 4-, 8-, 12-, and 16-weeks post-weaning (even though piglets were exposed to the MP only the first 48 h after weaning).Behaviors were recorded for the first 48 h of the study (2 days post-weaning) to identify the impact treatments had on aggression, feeding, and lying behaviors in weaned piglets relative to the control group. Behaviors are defined in Statistical analyses are the same as described above. This study had three treatments; however orthogonal linear contrasts were used to compare control with the combined MP treatments. This study showed that the MP response was clear 1 week after weaning based on body weights, ADG and the percentage of pigs that lost body. Thus, the 7-days bioassay was developed and used in the remaining studies to refine the formulation. In this bioassay, key measures were ADG the first 7 days after weaning, and the percentage of weaned pigs that lost body weight the first 7 days after weaning.The methyl ester form of fatty acids is more volatile than fatty acids alone. In this case, myristic acid is less volatile than methyl ester myristic acid . The infPrior to study three, we had not yet performed any sort of dose response study. Therefore, we sought to determine if pigs responded similarly with the concentration used above (the MAME formula) and a formulation that was 5 times higher . Study 2 identified that the Myristic Acid formula performed as well as the MAME formula. Rather than the sponge method, study 3 used ethylene vinyl acetate (EVA) plastic beads that were incubated with the pheromone concentrations for 24 h and then melted at 200 C for 11 min. EVA melts at this temperature and the mold we used produced a round cookie-like object CLO; see . After, Study 2 found that the MAME results were equivalent to the Myristic Acid formulation. Because of this, study 3 continued research with the Myristic Acid formula. This formula was diluted with di isopropyl adipate instead of 70% isopropyl. The CLOs were made with either a 1 ppm (100 μg) for low dose or 5 ppm for high dose (500 μg). Body weights were collected at time of weaning and 7 days post-weaning. Numbers and percentages of pigs losing weight after weaning were recorded. Again, key measures were ADG at 7 days post-weaning and the percentage of weaned pigs that lost body weight 7 days post-weaning.Products like air fresheners and area insecticides, are sold as an imbedded plastic material that releases the odor or chemical over time. The two most common plastic materials are EVA and Nylon. In this study we sought to determine (using our 7-days bioassay) if one form of plastic or the other would impact pig performance. Study 3 identified the lower concentration (100 μg) to produce similar results as the high dose (500 μg), so Study 4 focused on manufacturing the low dose into strips of Nylon and EVA plastic. The EVA beads CLO,  were plaA total of 60 weaned piglets were arranged by litter and gender into 15 pens (5 pens/treatment). Control pens received nothing. Nylon strips were cut into rectangular pieces (2 cm X 7 cm) and placed into locked plastic holsters with openings on the sides for the release of the pheromone. EVA CLOs, as described above, were suspended above the feed at the same height as the Nylon strips. Nylon strips and EVA cookies remained for 7 days. Weights were recorded at time of weaning and 7 days post-weaning onset. Key measures were ADG the first 7 days post-weaning and the percentage of weaned pigs that lost body weight 7 days post-weaning.via power test the sample size needed for a 7-days bioassay to determine that within a single study, treatment effects could be determined. Because in all studies the MP variations  did not differ, here we report the data as control vs. MP . Because they did not differ from control pig values, MAME and Nylon treatments were not included in the experiment-wise evaluation of the percentage of pigs losing weight in the first 7 days after weaning.To run through many iterations of MP delivery requires time, animals, and peoples' efforts. To reduce the time needed to move product development along, a simple, less time-intense bioassay was needed. Individual studies do not have to have significantly different treatments if one is simply interested in which is better among a small number of choices. Here we report one long-term study (study 1) and three bioassay studies (studies 2–4). The methods during the first 7 days of each of the four studies were identical; each study had a control and MP treatment groups. This meta-analysis or experiment-wise examination used the experiment and treatment (control vs. MP regardless of form) as the experimental unit. Each study generates only 1 mean per measure per treatment per study. Therefore, the four studies we summarize here represent an N of 4 experimental units per treatment . In addition, having the same methodology and the same control treatment over four studies gave us ample sample size to (a) demonstrate overall effects of control vs. MP and (b) estimate We sought confirmation that the MP was released from the differing plastic forms. Different application methods cause different release rates. Skatole is highly volatile and is used as a marker of MP release. Myristic Acid cannot easily be detected in the head space over the plastics we tested. Solid Phase Microextraction (SPME) was utilized to detect the releasing of the maternal pheromone molecules from the applicators in the study . SPME idP < 0.05). For most measures, MP delivered by sponge or bead caused equal behavior and performance. Feeding behavior among pigs with beads-MP was higher (P < 0.05) than sponge-MP during the first 2 h after weaning; but the average feeding behavior over 48 h was not different between sponge-MP and bead-MP. Likewise, for all measures of pig body weight and weight gain, sponge-MP induced similar performance as bead-MP exposed pigs.Piglets were placed in one of three treatments: control, sponge-MP, bead-MP. Weights for all treatment groups averaged 5.81 kg at the start of the study with no significant difference between treatment groups and control groups (SE = ± 0.53 kg). Control groups gained 0.04 kg per day while treatment groups gained 0.11 kg per day (P < 0.05) for sponge-MP and bead-MP compared to the control group. The significant difference of the treatment groups ADG compared to the control suggests that maternal pheromone influences feed intake in newly weaned piglets.Data during the weeks post-weaning are presented in P = 0.05) among MP-exposed pigs relative to control pigs. The effect is large—MP-exposed pigs were 4 kg heavier than control pigs 16 weeks after weaning. At other weight days (earlier weights- weeks 4 to 12), the means tended to be higher for MP-exposed pigs than control pigs, but none of these other weigh dates reached statistical significance.Pig growth was measured into the finishing phase at 16 wk post-weaning. ADG was higher the first week for MP-exposed weaned pigs compared with the control group. Pig body weight at 16 wk post-weaning was higher (P = 0.06) and an increase in feeding.Average pig behavior on the first 24 h after weaning is reported in 2 = 20.06, P < 0.01). That is, when aggression went down, feeding behavior went up.The feeding and aggressive behavior data over the 48 h after weaning are presented in Study 2 focused on the form of one molecule in the maternal pheromone formula to identify if using MAME might be better than Myristic Acid because MAME is more volatile. Body weights at the beginning of the study were uniform across all pens at an average 6.44 kg. Within this study, the two forms of Myristic Acid did not differ significantly from the control pigs nor from each other . HoweverLow dose and high dose versions were tested in our 7-days bioassay to identify the concentration at which piglets respond to MP exposure. Weights started at an average 6.8 kgs through each treatment group and were compared to weights at 7 days post-weaning. The control group gained 0.02 kg per day with no significant increase in weight due to treatment. Both treatment groups, as seen in study 1 and study 2, demonstrate a significant combined increase in weight of over 50% relative to the control group . The lowThis study evaluated two forms of plastic that are known to be used to release volatile molecules . Pigs in treatments exposed to either the EVA or Nylon had an increase in ADG the first 7 days post-weaning, but the effects were not statistically significant . Once agComparing the GC-MS of each group, EVA released more MP than the Nylon , 5. CompStudy 1 and the meta-analyses demonstrate that the MP was efficacious at improving pig post-weaning weight gain and the MP prevented many pigs from losing weight after weaning in general. The maternal pheromone induced this performance stimulation by increasing feeding behavior and reducing aggressive behaviors in the post-weaning environment. The responses we obtained were larger than our previous study . PreviouWe observed zero mortality in these studies. This would not be the case on most commercial farms. This work needs to be replicated and perhaps refined for an actual commercial environment which represents normal pig production.Feed consumption is low in the recently weaned pig and is a current challenge . The datThe 7-days bioassay accelerated our refinement of the best delivery options to get the MP near the pigs . The modClearly, weaned pigs that lose weight have poor welfare. Preventing that loss in body weight will improve pig welfare, as pigs that lose weight are believed to be more susceptible to disease and starvation. The MP may give the weaned pig an olfactory clue as to where the feed is and encourage them to eat. When feeding behavior goes up, aggression goes down (they cannot express both behaviors at the same time). Reduction in aggression at this age does not have a large economic impact, but it is positive for pig welfare. Moreover, increasing feeding behavior has pig performance and health benefits.We can now make some general conclusions about use of the MP to stimulate post-weaning performance and behavior. First, the effective dose is fairly wide. Although 1 ppm and 5 ppm gave similar results, we also recognize that the sponge, alginate beads, and EVA each release MP at different rates, yet they were all largely effective.One could ask why we do not put the MP in the feed. First, that would require regulatory approval which takes time, money, and may not be necessary if non-feed applications are effective. Second, we are trying to get the weaned pig to understand that this dry grain-based substance is its food rather than milk from its mother. Having the maternal odor near, but not in the food, gives the piglet the idea that food is in proximity of the MP. We would not recommend spraying the MP anywhere other than near the feed in the feeder. If one sprayed it all over the post-weaning pen, it would confuse the weaned pigs much like spraying pheromones in a forest disrupts mating behavior by confusing the insects and preventing insect mating . The immAnother indication that the effect is robust is that the MP has positive effects when delivered in many forms. Besides the many forms tested here, Iowa State Scientists had positive results diluting the MP in sunflower oil and our oOne can see about a 4 kg body weight advantage when the MP was used for 2 days after weaning. Few animal health products deliver this level of response. By considering that the post-weaning environment is deficient in the MP, adding this pheromone back into the weaning space restores greater  feed intake, produces less fighting, and causes greater weight gain. Producing both better performance and welfare.The MP has many applications beyond what is reported here. It is useful to attract pigs of any age to a device or food, and it may reduce stress when the pigs experience stressors like weaning or transport. Future studies will examine how to correct the olfactory environment present in production settings, known to be deficient in biologically relevant semiochemicals, as a means to stimulate health, productivity, and welfare.The original contributions presented in the study are included in the article/The animal study was reviewed and approved by Texas Tech University Animal Care and Use Committee (# 19104-12).JM conceived the project and supervised the studies. CA conducted most of the work. AG provided the technology for the alginate beads. MH assisted in the writing of the manuscript and its preparation for publication. All authors contributed to the article and approved the submitted version.This work was supported by Animal Biotech, LLC which provided funds to Texas Tech University for the conduct of this work.JM declares a potential conflict of interest in that he is the inventor and patent-holder of the MP technology reported here. The intellectual property is owned by Texas Tech University who licensed this technology to Animal Biotech, LLC.The remaining 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.