The probiotic Escherichia coli strain Nissle 1917 -LRB- EcN -RRB- stops acute diarrhoea in infants and toddlers In most cases , acute diarrhoea will become self-limiting during the first few days after onset . For young children , however , health risks may develop when the disease lasts longer than 3 days . The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 -LRB- EcN -RRB- solution than by administering a placebo . The safety of EcN were also assessed . A total of 113 children -LRB- aged 2 -- 47 months -RRB- with acute diarrhoea -LRB- > three watery or loose stools in 24 h -RRB- were randomised to either a group receiving the probiotic EcN suspension -LRB- n = 55 -RRB- or a group receiving the placebo suspension -LRB- n = 58 -RRB- in a confirmative , double-blind clinical trial . Depending on the age of patients , 1 -- 3 ml per day of verum suspension -LRB- 108 viable EcN cells per millilitre -RRB- or placebo were administered orally . The causes of the diarrhoea were viral rather than bacterial , but they were mainly unspecific infections . The median onset of treatment response -LRB- reduction of daily stool frequency to ≤ three watery or loose stools over at least 2 consecutive days -RRB- occurred more rapidly in the children receiving the EcN solution -LRB- 2.5 days -RRB- than in those receiving the placebo -LRB- 4.8 days -RRB- , a significant difference -LRB- 2.3 days ; p = 0.0007 -RRB- . The number of patients showing a response was clearly higher -LRB- p < 0.0001 -RRB- in the EcN group -LRB- 52/55 ; 94.5 % -RRB- than in the placebo group -LRB- 39/58 ; 67.2 % -RRB- . EcN was found to be safe and well-tolerated , and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers . Introduction Probiotics are non-pathogenic microorganisms -- mostly of human origin -- which confer health benefits to the host when administered in adequate amounts . They are considered to be a safe and effective part of the first-line therapy for acute diarrhoea in children and adults -LSB- 12 -RSB- . In addition , probiotics are able to prevent or improve not only gastrointestinal diseases such as inflammatory bowel disease , irritable bowel syndrome , infectious gastroenteritis or diverticular disease of the colon , but also to act in the prevention of allergic diseases . Various probiotics are commercially available in , for example , Europe , the USA and Japan where they are marketed as functional foods or probiotic drugs . To date , lactobacilli , bifidobacteria and Saccharomyces boulardii are the most commonly marketed probiotic active substances . Certain strains of Escherichia coli are also available in some European countries , the best known example of which is E. coli strain Nissle 1917 -LRB- EcN -RRB- . EcN is marketed as a probiotic drug in two galenic presentations for oral use : enteric-coated capsules and a suspension in which 1 ml contains 108 viable EcN cells . While capsules are mostly used in adults -LRB- e.g. Kruis et al. -LSB- 8 -RSB- -RRB- , the use of the suspension form is the most reasonable form in neonates , infants and toddlers . The purpose of the present trial was to examine the efficacy and safety of an EcN suspension administered to infants and toddlers suffering from acute diarrhoea of different causes in terms of normalising the stool frequency . Materials and methods Infants and toddlers treated for acute diarrhoea in the paediatric outpatient wards of 11 centres between February and April 2005 were eligible for enrollment in this study . This was a multicentre , prospective , confirmative , randomised , double-blind , placebo-controlled , parallel group clinical trial of phase III . It was carried out in accordance with the requirements of Good Clinical Practice and the Revised Declaration of Helsinki . The study was approved by the Independent Ethics Committee -LRB- IEC -RRB- of the Federal Agency of Drugs Quality Control , Moscow , Russia , and by the IEC of the State Enterprise Centre of Immunobiological Medicines at the Ministry of Health of Ukraine . Acute diarrhoea was defined as more than three watery-to-loose stools per day from an acute episode of non-bloody diarrhoea which did not persist longer than 3 successive days . For reasons of comparability , one of the exclusion criteria was a higher grade of dehydration -LRB- loss of body weight > 5 % ; hydration status was surveyed , rehydration was not implemented in low-grade dehydration -RRB- ; the most important inclusion and exclusion criteria are listed in Table 1 . The participant was assessed until ascertainment of response , 10 days at maximum . An overview of the study design is presented in Fig. 1 . A stool sample was taken at both the beginning and end of the study and checked for the presence of the following pathogens : Salmonella , Campylobacter , Yersinia , E. coli -LRB- ETEC , EPEC , EIEC , EHEC -RRB- , Shigella , Entamoeba histolytica , Cryptosporidium parvum and Rota - , Adeno - and Noroviruses . Table 1Inclusion and exclusion criteriaInclusion criteriaExclusion criteriaAge < 4 years at the time of enrolmentDehydration -LRB- > 5 % loss of body weight -RRB- More than three watery or loose non-bloody stools in a 24-h period that had not persisted for more than three consecutive daysParticipation in another clinical trialSigned informed consent by the parentsIntake of EcN within the past 3 months prior to enrolmentIntake of food supplements or drugs which contain living microorganisms or their metabolic products or components within 7 days prior to enrolment or during the trialOther antidiarrhoeal drugsAntibioticsBreast-feeding , Premature birthSevere or chronic disease of the bowel or severe concomitant diseasesFig . 1Study design . * Final visit Duration of treatment , which was until ascertainment of response , 10 days at maximum The parents were asked to maintain a daily record -LRB- diary -RRB- containing information on the number of stools , stool consistency , admixtures of blood or mucus , frequency of vomiting , abdominal pain and cramps and fluid intake as well as concomitant medication and general state of health . An assessment of general health was also documented during each control visit by the investigator and parents . The randomisation schedule was generated by means of SAS , ver . 9.1 -LRB- SAS Institute , Cary , N.C. -RRB- based on seed values dependent on a random number generator . The method of randomly permuted blocks was used -LRB- block size : 4 -RRB- . Study medication The drug being studied -LRB- verum -RRB- is a commercially available suspension for oral use that contains non-pathogenic E. coli strain Nissle 1917 -LRB- Mutaflor suspension ; Ardeypharm , Herdecke , Germany , with 108 viable microorganisms per millilitre -RRB- . As placebo , we administered an identical preparation consisting of a suspension devoid of the active substance . In accordance with good clinical practice -LRB- GCP -RRB- , identical containers were used in order to guarantee a concealed random allocation both to the parents and the study personnel involved . Depending on the age , daily doses of the study medication -LRB- EcN or placebo -RRB- were : Infants < 1 year1 ml once dailyToddlers ≥ 1 to ≤ 3 years1 ml twice dailyToddlers > 3 to < 4 years1 ml three times daily The parents received a diary in which the intake of the trial medication was documented . The investigator checked the entries for completeness and plausibility . The compliance was also evaluated by comparing the amount of trial medication handed out with that returns . Outcome The primary effect criterion was the time to response . Treatment response was defined as a reduction in stool frequency to ≤ three watery or loose stools in 24 h over a period of at least 2 consecutive days . Secondary effect criteria included the response rate , stool consistency , abdominal pain and cramps , body temperature , frequency of vomiting , occurrence of adverse events and tolerance to the study medication . Statistical analysis The study was conducted according to a three-stage group sequential test design -LRB- O'Brien / Fleming type -RRB- with possible sample size adaptation after the two planned interim analyses -LSB- 9 -RSB- . A time-to-response analysis was performed -LRB- Kaplan-Meier method ; log-rank test to test the superiority of EcN compared to placebo ; overall type-I error rate α = 0.025 ; one-sided -RRB- . The response rates were also computed and compared between treatment groups by means of Fisher 's exact test -LRB- one-sided ; exploratory -RRB- . The intention-to-treat -LRB- ITT -RRB- data set included all randomised patients who took at least one dose of study medication -LRB- primary analysis -RRB- , whereas patients with major protocol violations were excluded from the per-protocol -LRB- PP -RRB- analysis . The analysis sets were defined in a blind review of the data . The sample size was estimated prospectively using ADDPLAN ver . 3.0 . An independent data monitoring committee -LRB- IDMC -RRB- was responsible for reviewing the results of the interim analyses and giving recommendations . Two interim analyses were performed , resulting in continuation of the study with the pre-planned sample sizes . Results Baseline data A total of 113 infants and toddlers between 2 and 47 months of age with acute diarrhoea were admitted to the trial . All patients were Caucasian . The patients were randomly allocated to either the EcN group -LRB- 55 patients -RRB- or the placebo group -LRB- 58 patients -RRB- -LRB- Fig. 2 -RRB- . No relevant differences between the groups were observed in terms of gender , age , height , weight and BMI of the patients -LRB- Table 2 -RRB- . The vast majority of patients had an average body development and a good nutritional status , but reduced appetite was reported . There were also no differences in systolic and diastolic blood pressure , heart rate and body temperature between the two treatment groups at baseline . Fig. 2Diagram of participant flowTable 2Baseline data for the two treatment groupsEcN -LRB- n = 55 -RRB- Placebo -LRB- n = 58 -RRB- Male gender 32 -LRB- 58.2 % -RRB- 32 -LRB- 55.2 % -RRB- Age -LRB- median -RRB- 21 months23 monthsHeight -LRB- median -RRB- 83 cm83 cmWeight -LRB- median -RRB- 12.7 kg12 .6 kgBMI -LRB- median -RRB- 17.4 kg/m217 .2 kg/m2Mean duration of diarrhoea1 .4 days1 .6 daysMean stool frequency5 .0 per day5 .1 per dayPossible causes for the current acute diarrhoea episodePrevious antibiotic treatment2 -LRB- 3.6 % -RRB- 4 -LRB- 6.9 % -RRB- Virus infections 16 -LRB- 29.1 % -RRB- 19 -LRB- 32.8 % -RRB- Bacterial infections9 -LRB- 16.4 % -RRB- 4 -LRB- 6.8 % -RRB- Unspecified infections25 -LRB- 45.5 % -RRB- 29 -LRB- 50.0 % -RRB- Other causes3 -LRB- 5.5 % -RRB- 2 -LRB- 3.4 % -RRB- There was no difference in the duration of the current acute diarrhoea episode between patients in the EcN group and placebo group -LRB- EcN : 1.4 ± 0.6 days , mean : 1.0 days ; placebo : 1.6 ± 0.6 days , mean : 2.0 days -RRB- . The number of infections during the past 12 months was ≤ five in 55/55 patients -LRB- 100 % -RRB- of the EcN group and 56/58 patients -LRB- 96.6 % -RRB- of the placebo group . Infections as a cause of the acute diarrhoea were more often viral than bacterial . However , unspecific infections were the most common -LRB- Table 2 -RRB- . The number and proportion of patients with pathogenic microorganisms were slightly higher in the EcN group -LRB- 27/55 patients -RRB- than in the placebo group -LRB- 21/58 patients -RRB- at baseline . This difference was not statistically significant . Data analyses All efficacy analyses were originally designed to be performed on both the ITT and PP data sets . However , as the ITT and PP data sets were identical in this study -LRB- n = 113 patients -RRB- , only the ITT data are evaluated here . All safety analyses were performed on the ITT data set . Primary objective The median time to response was 2.5 days in the EcN group and 4.8 days in the placebo group , i.e. treatment with EcN shortened the duration of diarrhoea by 2.3 days . Statistical testing revealed that the EcN treatment was significantly superior to that of the placebo in terms of time to response -LRB- p = 0.0007 ; overall p value of the group sequential test design -RRB- -LRB- Fig. 3 -RRB- . Analysis by centre showed no difference in the number of responders between treatment groups . Fig. 3Time-to-response curves : Kaplan-Meier analysis -LRB- ITT analysis -RRB- In total , diarrhoea was stopped in 52/55 patients -LRB- 94.5 % -RRB- in the EcN group and 39/58 patients -LRB- 67.2 % -RRB- in the placebo group within 10 days . Fourteen patients dropped out of the trials -LRB- EcN , n = 1 ; placebo , n = 13 -RRB- because of unsuccessful therapy . The diarrhoea did not cease within 10 days of treatment in two patients of the EcN and six patients of the placebo group . Secondary objectives An exploratory comparison showed a significant difference in the number of responders between the treatment groups -LRB- p < 0.0001 ; ratio of rates : 1.406 ; 95 % CI : 1.162 -- 1.701 -RRB- . A cumulative presentation of the number of responders on each study day showed a difference between EcN - and placebo-treated patients starting on day 3 -LSB- EcN 34/55 -LRB- 61.8 % -RRB- vs. placebo 24/58 -LRB- 41.4 % -RRB- ; ratio of rates : 1.494 ; 95 % CI : 1.032 -- 2.163 -RSB- -LRB- Fig. 4 -RRB- . The difference increased until day 5 -LSB- EcN 45/55 -LRB- 81.8 % -RRB- vs. placebo 30/58 -LRB- 51.7 % -RRB- ; ratio of rates : 1.582 ; 95 % CI : 1.198 -- 2.089 -RSB- and then decreased slightly from day 6 to the end of study -LSB- EcN 52/55 -LRB- 94.5 % -RRB- vs. placebo 39/58 -LRB- 67.2 % -RRB- ; ratio of rates : 1.406 ; 95 % CI : 1.162 -- 1.701 -RRB- . Fig. 4Response rates among the patients receiving the EcN solution -LRB- n = 55 -RRB- and placebo -LRB- n = 58 -RRB- during the course of the study Prior to the treatment regimen , almost no infant had a normal stool consistency . During the course of the study the patients of the EcN group showed a more pronounced improvement than their counterparts in the placebo group . The same trend was observed for the disappearance of abdominal pain -LRB- 28/30 EcN patients vs. 24/33 placebo patients -RRB- and abdominal cramps -LRB- 17/18 EcN patients vs. 21/26 placebo patients -RRB- -LRB- Table 3 -RRB- . Table 3Improvement of symptoms after treatment EcN -LRB- % -RRB- Placebo -LRB- % -RRB- Normal stool consistency78 .440.5 No abdominal pain93 .372.7 No abdominal cramps94 .480.8 In addition , the general state of health , as assessed by the investigator during clinical examinations or by the parents by means of the diary , of the patients in the EcN group improved more clearly than that of the patients in the placebo group -LRB- data not shown -RRB- . Body temperature showed an almost identical decrease over time in both treatment groups -LRB- EcN : − 0.5 ± 0.4 °C ; placebo : − 0.4 ± 0.5 °C -RRB- . The number of vomiting episodes was very small at baseline in all patients and decreased to 0 % in both groups . In principle , body weight and the status of dehydration did not show any changes from baseline to the end of study in either treatment group . Only one patient in the placebo group experienced mild dehydration . From baseline to study termination , pathogenic microorganisms disappeared in a similar number of patients in both treatment groups -LRB- 14/27 patients in the EcN group and 12/21 patients in the placebo group -RRB- . In the patients who were free from infectious agents at baseline , pathogenic microorganisms were detected at the end of study in 3/28 and 6/37 patients in the EcN and placebo group , respectively . Tolerance to treatment The study medication was well tolerated . Only 2/55 patients -LRB- 3.6 % -RRB- in the EcN group and 2/58 patients -LRB- 3.4 % -RRB- in the placebo group experienced one adverse event -LRB- AE -RRB- each . These were rhinitis and abdominal pain in the EcN-treated patients and two cases of acute otitis media in the patients receiving the placebo . According to the European Medicines Agency -LRB- EMEA -RRB- classification , none of these AEs are rated as `` serious '' or `` severe '' -LRB- regulatory guidance CPMP/ICH/377 / 95 -RRB- . The two placebo-treated patients with otitis media were removed from the study due to the AE being intolerable . For the two AEs in patients receiving the EcN treatment , complete recovery was documented . According to the parents , tolerance to treatment was slightly better in the EcN group than in the placebo group , whereas no notable difference was observed by the investigators -LRB- Table 4 -RRB- . Table 4Tolerance to treatment in the two treatment groups Assessed by parentsAssessed by investigators EcNPlaceboEcNPlaceboVery good11/55 -LRB- 20.0 -RRB- a4/58 -LRB- 6.9 -RRB- 5/55 -LRB- 9.1 -RRB- 4/58 -LRB- 6.9 -RRB- Good44/55 -LRB- 80.0 -RRB- 53/58 -LRB- 91.4 -RRB- 50/55 -LRB- 90.9 -RRB- 53/58 -LRB- 91.4 -RRB- Poor0/55 -LRB- 0.0 -RRB- 1/58 -LRB- 1.7 -RRB- 0/55 -LRB- 0.0 -RRB- 1/58 -LRB- 1.7 -RRB- aPercentage is given in parenthesis Discussion The aim of this multicentre , prospective , confirmative , randomised , double-blind , placebo-controlled clinical trial of phase III was to investigate the therapeutic efficacy and safety of orally administered EcN in treating acute diarrhoea in infants and toddlers . The results showed that EcN was superior to the placebo in terms of both time to response and response rate . The difference in median duration of diarrhoea -- 2.3 days -- was statistically significant and also clinically important . Acute diarrhoea in children is very often self-limiting within a few days . However , toddlers and young infants are in danger of developing dehydration and a deteriorating general health . Therefore , a fast-tracking antidiarrhoeal treatment would be beneficial . Several investigations have been carried out with probiotics for the treatment of acute gastroenteritis , and different meta-analyses and systematic reviews have been published in this field . All of these have demonstrated the efficacy of probiotics in treating or preventing diarrhoea . On average , the treatment of diarrhoea with lactobacilli , bifidobacteria and/or S. boulardii shortened the duration of diarrhoea by only 0.5 -- 1.5 days -LSB- 4 , 12 , 14 , 18 , 19 -RSB- . Szajewska and Mrukowicz reviewed ten randomised , double-blind , placebo-controlled studies and concluded that the administration of probiotics led to a substantial reduction in the duration of acute diarrhoeal symptoms : an average of 20 h -LSB- 18 -RSB- . Moreover , a meta-analysis of nine clinical trials conducted by D'Souza et al. demonstrated that probiotics effectively prevented antibiotic-associated diarrhoea -LSB- 4 -RSB- . The work of van Niel et al. included nine randomised controlled studies with lactobacilli in acute infectious diarrhoea in children . In these studies , the duration of diarrhoea was significantly reduced by an average of 0.7 days along with the stool frequency -LSB- 19 -RSB- . Most recently , McFarland et al. examined the efficacy of probiotics in paediatric diarrhoea by analysing 39 randomised , controlled and blinded clinical trials comprising a total of 41 probiotic treatment arms -LSB- 12 -RSB- . Of these , 32 -LRB- 78 % -RRB- reported efficacy . The latest meta-analysis of 39 trials by Sazawal et al. showed that probiotics prevented acute diarrhea , with a risk reduction among children off 57 % -LRB- range : 35 -- 71 % -RRB- -LSB- 14 -RSB- . Diarrhoea is one of the best-studied indications for probiotics , and treatment with EcN has been found to stop acute diarrhoea more rapidly than other probiotics . The efficacy of EcN was confirmed by a second multicentre , prospective , randomised , double-blind , placebo-controlled phase III study conducted by our group -LSB- 7 -RSB- . In that study , children with prolonged diarrhoea treated with EcN showed a more rapid onset of response to treatment than those treated with placebo -LRB- median : 2.4 vs. 5.7 days ; p < 0.0001 -RRB- . There was also a remarkable difference in the response rates , as determined on days 14 -LRB- EcN : 93.3 % ; placebo : 65.8 % -RRB- and 21 -LRB- EcN : 98.7 % ; placebo : 71.1 % -RRB- , thus showing a statistically significant superiority of EcN on both days -LRB- p = 0.0017 and p < 0.001 , respectively -RRB- . In the present trial , high initial response rates in both groups represent the spontaneous healing known for acute gastroenteritis . The superiority of the EcN treatment became increasingly noticeable from 3 . The healing process was markedly faster in the EcN-treated patients than in the patients receiving placebo , a result which underlines the high efficacy of this probiotic . The relatively high number of children with unspecific diarrhoea corresponds quite well to the frequent failure to detect the responsible pathogen in routine analyses . This is the reason why the results of this study are not helpful in answering the question whether EcN is more efficient in bacterial or viral diarrhea . This question should be addressed by future studies . In the present study , EcN was safe and well-tolerated . There was no difference between the EcN and placebo treatments in terms of AEs , body weight , stool examinations and the assessment of tolerance . This result is in accordance with experience from clinical trials in premature and fullterm newborns where EcN was not only very safe but improved the microbial intestinal milieu of the treated infants and reduced the risk of acquiring pathogens early in life -LSB- 3 , 10 , 11 -RSB- . It has also been shown that prolonged colonisation with EcN protected infants at an age of 6 -- 12 months from flatulence , diarrhoea or constipation when given immediately on the first 5 days after birth -LSB- 16 -RSB- . Our understanding of the effects of probiotics and their numerous modes of action has grown substantially in recent years . With regard to gastroenteritis , probiotics may improve symptoms by several mechanisms , including : competition with pathogens -LRB- for adherence to intestinal epithelium , for growth and survival in the gut -RRB- and inhibition of pathogen overgrowth ; secretion of bacteriostatic/bactericidal peptides -LRB- e.g. colicins , microcins -RRB- ; enforcement of intestinal barrier function and reduction of microbial translocation ; modulation of immune responses -LRB- local and/or systemic , e.g. stimulation of secretion of IgA by lymphocytes and defensins by enterocytes -RRB- . All of these mechanisms of action have been shown for E. coli strain Nissle 1917 . The antagonistic activity of EcN against pathogens has been demonstrated in vitro in animal models and in humans -LSB- 1 , 10 , 13 , 17 -RSB- . In a pig model of intestinal infection , EcN was able to prevent acute secretory diarrhoea -LSB- 15 -RSB- . Among many other strain-specific characteristics -LSB- 2 , 5 , 6 -RSB- , EcN exerts an intense immunomodulatory effect in children -LSB- 3 , 11 -RSB- . Here , EcN was found to stimulate the production of antibodies of mucosa-associated B lymphocytes and the systemic production of antibodies -LRB- IgM , IgA -RRB- in premature and fullterm children . Conclusion In summary , EcN showed a significant superiority to placebo in the treatment of acute diarrhoea in infants and toddlers . EcN treatment also improved the general state of health and its administration was safe and well tolerated . Electronic supplementary material Below is the link to the electronic supplementary material Statistical analysis -LRB- DOC 31 kb -RRB-

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B I O B O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O B I O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O 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acute diarrhoea
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escherichia coli nissle 1917
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probiotic
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Joint-action coordination in transferring objects Here we report a study of joint-action coordination in transferring objects . Fourteen dyads were asked to repeatedly reposition a cylinder in a shared workspace without using dialogue . Variations in task constraints concerned the size of the two target regions in which the cylinder had to be -LRB- re -RRB- positioned and the size and weight of the transferred cylinder . Movements of the wrist , index finger and thumb of both actors were recorded by means of a 3D motion-tracking system . Data analyses focused on the interpersonal transfer of lifting-height and movement-speed variations . Whereas the analyses of variance did not reveal any interpersonal transfer effects targeted data comparisons demonstrated that the actor who fetched the cylinder from where the other actor had put it was systematically less surprised by cylinder-weight changes than the actor who was first confronted with such changes . In addition , a moderate , accuracy-constraint independent adaptation to each other 's movement speed was found . The current findings suggest that motor resonance plays only a moderate role in collaborative motor control and confirm the independency between sensorimotor and cognitive processing of action-related information . Introduction Given the strong inclination that people have towards behavioral mimicry when they are jointly involved in walking or speaking -LRB- Chartrand and Bargh 1999 ; Lakin et al. 2003 -RRB- , can we also demonstrate co-actors adopting each other 's movement patterns in the simple task of transferring objects ? If an object relevant for my own actions is placed in front of me at a high speed , shall I then automatically pick it up and transfer it also with a high speed or will I stick to my own , preferred speed ? Furthermore , will an observer be sensitive to the height of the movement trajectory with which an object is placed within reach as a potential cue of that object 's weight ? Detailed questions surrounding the potential transfer of movement kinematics in a shared action sequence as specified above have not yet been systematically investigated -LRB- cf. Sebanz et al. 2006 -RRB- . The little work that has been done in this area was limited to unintentional synchronization of arm movements in pendulum swinging -LRB- Schmidt and O'Brien 1997 -RRB- , incidental entrainment of leg movements when dyads solve a puzzle through dialogue -LRB- Shockley et al. 2003 -RRB- , and the kinematic characteristics of cooperative versus competitive grasping movements -LRB- Georgiou et al. 2007 -RRB- . A recent model of joint action by Oztop et al. -LRB- 2005 -RRB- that makes relevant claims regarding joint-action coordination in sequential task performance presumes that when a person observes someone else 's actions she automatically will activate her own action system not only to understand the behavior of the actor being observed -LRB- Rizzolatti and Craighero 2004 -RRB- but also to infer that actor 's intentions -LRB- cf. Wolpert et al. 2003 ; Iacoboni et al. 2005 -RRB- . The example Oztop et al. -LRB- 2005 -RRB- mentioned in this context concerns the implied meaning that is conveyed by the specific way in which people may handle a tool . For example , whereas holding a hammer with a usual grip around its handle is very likely to signal the intent of hammering , holding the hammer with a power grip around its face communicates the intention to handing over the tool to someone else rather than start hammering with it oneself . Of course , which semantics are primed by the way in which a tool is handled will depend on the shared knowledge of how the tool is used for the general purpose it was designed for -LRB- see also Cuijpers et al. 2006 -RRB- . In the present study we were neither interested in what a particular act might convey to an observer in terms of action semantics -LRB- Oztop et al. 2005 -RRB- nor how cooperative or competitive contexts are differentially reflected in the prehension kinematics of dyads -LRB- Georgiou et al. 2007 -RRB- . Instead , we focused on the extent to which an observer in her subsequent movements is influenced by specific kinematic features of a co-actor 's movements bringing the object within reach . Since the participants in the present study were asked to perform complementary acts rather than identical ones this research question is therefore only indirectly related to topics like behavioral mimicry and imitation -LRB- Koski et al. 2003 -RRB- . Our reasoning about the possible transfer of kinematic movement parameters from one actor to another was that if during action observation people internally simulate the movements that they observe -LRB- Gallese and Goldman 1998 ; Rizzolatti and Craighero 2004 -RRB- , then the kinematic features of these simulated movements might as well be re-used for a related , self-generated movement that , in time , closely follows the observed one even when this future movement is complementary in nature . Economizing on parameter remapping costs formed the basis of this expectation -LRB- cf. Rosenbaum et al. 1986 -RRB- . As regards inference making we were interested in the extent to which people derive the weight of an object when seeing someone else picking up and transporting the object . A similar matter has been investigated in an fMRI study by Grezes et al. -LRB- 2004 -RRB- but their experiment was primarily designed to find the brain correlates of action observation in the context of deception . To this end these researchers used pictures of an accomplice lifting boxes as if they were heavy or when they were actually heavy . In the present study , however , deceit was not the issue of investigation . Moreover , the object-weight dependent variations in movement kinematics were more subtle than in the Grezes et al. -LRB- 2004 -RRB- study and related studies on box lifting by Hamilton et al. -LRB- 2007 -RRB- and Kingma et al. -LRB- 2005 -RRB- as we will explain next . To gain further insight into the extent to which task-dependent kinematic variations affect the subsequent complementary actions of a co-actor , we exploited two widely investigated motor-control paradigms , viz. the speed-accuracy trade-off -LRB- Fitts 1954 ; Fitts and Peterson 1964 -RRB- and size -- weight illusion -LRB- Charpentier 1891 -RRB- . Figure 1 depicts the transportation task that we used for this purpose . First , one of the two actors -- the ` putting-actor ' -- was asked to pick up a vertically positioned cylinder from a nearby location on the table and to put that cylinder into a circular-shaped target area in the middle of the table , i.e. , within reach for the other actor . Subsequently , the other actor -- the ` fetching-actor ' -- was asked to fetch the cylinder from where the putting-actor had left it , and to reposition it , also in a circular-shaped , nearby target area . The fetching-actor was instructed not to pick up the cylinder before the putting-actor had released it . Fig. 1Top view of experimental setup depicting the experimental task . The dashed squares represent the starting areas for the -LRB- right -RRB- hand movements of both actors . At the filled circle a cylinder was positioned which had to be picked up by the putting-actor , repositioned in the central circular target area where the fetching-actor was to pick it up and place it in the target circle in the vicinity of her own starting area Three task variables were manipulated , viz. the size of the target areas in which the actors were to successively reposition the cylinder and the size and weight of the to-be-transported cylinder . The size of the target areas was expected to modulate the actors ' movement-speed and the size and weight properties of the cylinders were thought to affect the height with which the actors would lift the cylinders during transport . Before elaborating on our rationale it is important to mention that task conditions were kept constant within trial blocks of three repetitions to examine how quickly the dyads adapted to the between trial-block changes in the experimental conditions . All factors other than the repetition factor were randomized across the trial series and dyads , and at the start of each trial block the participants were unaware of the experimental conditions of that particular block -LRB- see `` Method '' -RRB- . Two types of potential transfer of movement kinematics were foreseen in our experimental task . First , it was expected that an incorrectly anticipated weight of a to-be-picked up cylinder would be reflected in the height with which an actor would lift that cylinder -LRB- cf. Grezes et al. 2004 -RRB- . A lighter than expected cylinder was assumed to be lifted higher than a heavier one and vice versa , i.e. , a heavier than expected cylinder was assumed to be lifted less high than a lighter one . Furthermore , if the fetching-actor would infer the weight of the cylinder that was transported by the putting-actor by observing her movements , then the fetching-actor was expected to have a more precise initial estimate of the weight of the to-be-transported cylinder than the putting-actor . The degree to which any surprise effect due to a wrongly anticipated object weight would transfer from the putting-actor to the fetching-actor thus formed a test as to whether or not the fetching-actor had actually inferred the cylinder weight . In repetitions two and three of each trial block both actors could rely , of course , on their sensorimotor memory -LRB- see Nowak and Hermsdorfer 2003 -RRB- as regards the object weight since in these trials they already had handled that particular cylinder in the previous -LRB- two -RRB- trial -LRB- s -RRB- of the trial block . To investigate the predicted object-weight dependent interpersonal kinematic transfer effects , we factorially combined two cylinder weights -LRB- light vs. heavy -RRB- with two cylinder sizes -LRB- small vs. large -RRB- yielding four cylinders . The size -- weight illusion that results from this particular combination of object features reflects the fact that people perceive a smaller of two equally-massed objects as heavier . For one of the suggested explanations of this illusion , we refer to Flanagan and Beltzner -LRB- 2000 -RRB- . The size -- weight illusion is so prominent that it also yields its typical effects when wielding a small and a large object of equal weight in the left and right hand simultaneously suggesting the distorted perception is due to sensory invariants rather than inferences -LRB- Amazeen and Turvey 1996 -RRB- . Irrespective of any size -- weight illusion effects , we expected the cylinder-weight variations to result in larger between trial adaptation effects on the height with which the participants would lift the cylinders than the cylinder-size variations -LRB- Gordon et al. 1991a , b -RRB- . We thus examined the extent to which the weight of an object carried from one position to another would be inferred by an observer . If the observer , i.e. , the fetching-actor , would not infer the weight of the transferred cylinder , then the surprise-effect expressed in the lifting height of the fetching-actor should be equally large as that in the putting-actor . Conversely , should the fetching-actor correctly infer the weight of the object by observing the putting-actor lifting and repositioning the cylinder , then the fetching-actor should be able to anticipate the cylinder 's weight better and not show such large surprise effects as the putting-actor would . A second manipulation targeted the extent to which the two actors would adopt each other 's movement speed in the face of variations of movement-accuracy constraints . If merely by observing someone else 's movements , one would be inclined to adopt a similar speed in a subsequent complementary movement , then confronting two actors with different target area sizes was expected to modulate their speed differently than when the actors would be confronted with these target areas individually . The rationale here was based on Fitts ' law , which states that one 's movement speed systematically varies with the size of the target area -LRB- Fitts 1954 ; Fitts and Peterson 1964 ; Mottet et al. 2001 -RRB- . The smaller the target area to reach for , the lower the movement speed due to the higher accuracy demands that are associated with small target areas . In the present study we manipulated the target area sizes of the first and the second actor separately , where the size was either small -LRB- diameter of 9 cm -RRB- or large -LRB- diameter of 18 cm -RRB- . If both actors had identical -LRB- either small or large -RRB- target area sizes , their movement speeds were most likely to become similar under the assumption that there would be a strong tendency to adopt each others ' speed . If this tendency of movement speed transfer was strong enough , then violations of Fitts ' law in the fetching-actor could be expected under conditions in which the two actors were confronted with dissimilar target area sizes . In sum , in the present study consisting of a sequential motor task involving two actors we tested whether lifting height -- a parameter that potentially could reveal an object 's weight -- would be picked up by an observing co-actor and determine her subsequent handling of that object and whether she would be inclined to adapt her speed to the observed speed , or , alternatively , whether the interpersonal transfer of kinematic parameters would be incidental in nature , i.e. , unrelated to the task constraints with which the individuals of the dyad were confronted . Method Participants Fourteen right-handed adult dyads participated in the experiment . Their ages ranged from 18 to 30 years ; mean age was 22 ± 2 years . The 28 participants , 22 females and 6 males , formed 8 female dyads and 6 dyads of mixed gender . They received either course credits or payment -LRB- 6 euros per hour -RRB- for their participation . Each participant signed an informed consent form . The study was approved by the local ethics committee and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki . Materials A Microsoft Windows-2000 controlled PC was used to control the stimulus events and data collection . Two synchronized 3D infrared motion-tracking systems -LRB- Optotrak ™ , Northern Digital , Waterloo , Canada -RRB- were used to record the displacements of the wrist , thumb and index finger of the right hand of the two actors . Three infrared-light emitting diodes -LRB- IREDs -RRB- were used per participant . The IREDs were fixated on the wrist joint and the distal phalanxes of the index finger and thumb of the right arm of the participants . The IRED-position data were sampled at a rate of 100 Hz with accuracy better than 0.2 mm in X , Y and Z directions . Each participant wore a pair of earphones through which a repetitive sound was presented at approximately 60 dB throughout the experiment . This prevented the participants from speaking to each other and hearing any task-related noise , e.g. , due to the cylinders making contact with the tabletop at completion of the transport phases . Each participant also wore a facial mask to avoid communication by means of facial cues . The participants were seated comfortably at opposite sides of a table on top of which a 1-cm thick marble plate was placed to prevent any object-weight information being conveyed from one actor to the other by means of vibrations via the table surface . Four cylinders of 25 cm height were used , two with a diameter of 2.5 cm and two with a diameter of 6.5 cm . Two cylinders had a lightweight of 230 g and two cylinders had a weight of 835 g. To avoid any potential confounding between the effects of cylinder and target-area size all cylinders were given a 4-mm thick , circular base of 8 cm in diameter . This ensured that the thin and thick cylinders had the same size support base and could be repositioned in a comparable stable way which was a factor that also could contribute to the accuracy constraints since the participants were asked to place the cylinders on small and large circular target areas that were clearly marked on the table surface . Procedure and task The experiment consisted of three sections . In the first section one of the two participants performed 48 single-actor control trials consisting of picking up and repositioning in random order , but blocked -LRB- three repetitions per block -RRB- , the four cylinders without the presence of the other participant . In the second section , the other participant performed 48 single-actor control trials , also alone . In the third section the two participants of the dyad performed 96 joint-action experimental trials . The 48 control trials per participant resulted from three blocked replications -LRB- n = 3 -RRB- of each of the factorial combinations of the factors size of starting area -LRB- small vs. large -RRB- , size of target area -LRB- small vs. large -RRB- , cylinder weight -LRB- light vs. heavy -RRB- and cylinder size -LRB- small vs. large -RRB- . The number of joint-action experimental trials was twice the number of single-actor control trials . In the joint-action experimental trials each participant was given in half the trials the role of putting the cylinder in the centre of the table , and in the other half of the trials the role of fetching the cylinder from the centre of the table -LRB- see Fig. 1 -RRB- . The role was randomly assigned to the trial blocks of three repetitions . In their control trials the participants of dyads 1 -- 9 -LRB- arbitrary numbered -RRB- performed the fetch-part of the experimental task , i.e. , at the start of their control trials they were confronted with a cylinder that was placed in the middle of the table and their task was to pick it up and place it in the area which was closest to their own starting position . Dyads 10 -- 14 performed in their control trials the put-part of the experimental task , i.e. , at the start of each trial they found the cylinder on the area closest to themselves and they were instructed to put the cylinder in the target area at the centre of the table . The data analyses showed that there were no systematic differences between the two groups of dyads as far as the targeted research questions concerned so the comparisons with the control trial data will not be addressed further in the remainder of this paper . The experiment was conducted by two experimenters who sat behind the participants . Each experimenter had a clear view on a separate computer screen which displayed information that specified the experimental conditions of every trial . In-between trials the participants were asked to close their eyes . After both participants had closed their eyes , the experimenters put the appropriate target pads on the table as well as the appropriate cylinder in the starting area of the putting-actor . Then , the two experimenters simultaneously tapped the participants on their lower arm , which indicated that they could open their eyes to start performing the trial . At the same time one of the experimenters started the movement recording . The standard event sequence in a joint-action experimental trial was as follows . At the start of each trial one of the two actors , i.e. , the putting-actor , found in a location close to the starting position of the right hand a cylinder that had to be picked up and moved to the target area in the centre of the tabletop -LRB- see Fig. 1 -RRB- . Only after the putting-actor had released the cylinder was the fetching-actor allowed to pick up the cylinder and to reposition it in a target area adjacent to her . The action sequence was to be completed within 8 s during which the displacements of the wrist and finger IREDs on both actors were sampled at a rate of 100 Hz . After every 48 trials , or whenever they asked , the participants were offered a 10-min break . Data analysis The raw IRED position data were smoothed with a second-order , low-pass Butterworth filter with a cut-off frequency of 8 Hz . Subsequently , the position data were segmented on the basis of the tangential velocity -- time functions of the IREDs on the wrists of the two actors -LRB- see top-left graph in Fig. 2 -RRB- . Fig. 2Kinematics derived from position data of infrared-light emitting diode -LRB- IRED -RRB- on tip of the thumb , tip of the index finger and wrist as obtained in a prototypical trial . Green -LRB- light grey -RRB- functions are from the putting-actor , red -LRB- dark grey -RRB- functions are from the fetching-actor . The top-left graph shows the tangential wrist-velocity time functions , the top-right graph a 3D rendering of finger-thumb displacements , the bottom-left graph shows the aperture-time functions , and the bottom-right graph shows the height -LRB- in cm above the table surface -RRB- of the midpoint between the thumb and index-finger IREDs The movement sequence of each actor was segmented into three intervals , the first interval corresponding to grasping the cylinder starting with the right hand in the home-position on the edge of the table and ending with finger and thumb making contact with the object , the second interval corresponding to the transportation of the cylinder to the target area -LRB- see put and fetch legends in Fig. 2 -RRB- , and the third interval corresponding to the participant 's hand returning to the home-position . The intervals were detected by a semi-automatic search procedure for relevant local minima in the tangential velocity profiles of the wrist movements . The time indexes thus found could be adjusted with an interactive computer program using a cross-hair whenever the experimenter considered the segmentation inaccurate . Following segmentation , the data analyses focused on the displacements of the IREDs located on the tip of the thumb and index finger of each of the two actors . The top-right graph of Fig. 2 shows a 3D-graph of the typical finger -- thumb displacements of the putting-actor -LRB- in green or light grey -RRB- and the fetching-actor -LRB- in red or dark grey -RRB- . The three cylinders were added to this graph post hoc to indicate the phasing of the displayed movement patterns . The bottom-left graph of Fig. 2 shows the aperture-time functions of both actors . This figure was used to inspect the grasping behavior of the participants . Systematic aperture overshoots just prior to object contact and upon object release were visually checked by the experimenter to verify whether the task of each actor was performed as requested . The bottom-right graph of Fig. 2 shows the height in the Z-dimension -LRB- perpendicular to the table surface -RRB- of the midpoint between the 3D positions of the IREDs on the thumb and index finger of each actor . This parameter reflected the surprise effects due to unexpected between-trial cylinder-weight changes on the lifting height , which was defined as the difference in the vertical position of the midpoint between the tips of the digits at the time of grasping the cylinder and the maximum height realized during transportation . In the second interval of each of the three-segment movement patterns , i.e. , the green function for the putting-actor and the red function for the fetching-actor , this lifting height reflected the height with which the participants lifted the cylinder while transporting it to their target area . The maximum lifting height -LRB- in cm -RRB- and the mean tangential wrist speed -LRB- in cm/s -RRB- realized by each actor during cylinder transport were used for further analyses . Statistical evaluation of the data consisted of repeated measures ANOVAs of which the designs are described in the relevant paragraphs in the results section or targeted t tests to evaluate specific hypotheses in more detail . Results Effects of cylinder properties Figure 3 shows the means and standard errors of the lifting heights realized by the putter and fetcher as a function of cylinder mass , cylinder size and the repetition factor . Table 1 summarizes the results of the repeated measures ANOVA that was conducted to evaluate these effects with a factorial design consisting of the within-dyad factors 2 roles -LRB- put vs. fetch -RRB- × 2 object masses -LRB- light vs. heavy -RRB- × 2 object sizes -LRB- small vs. large diameter -RRB- × 3 repetitions . As expected , the light cylinders were lifted higher than the heavy ones -LSB- F -LRB- 1,13 -RRB- = 86.5 , P < 0.001 -RSB- . This effect interacted with object size -LSB- F -LRB- 1,13 -RRB- = 14.4 , P < 0.01 -RSB- in line with the size -- weight illusion . For the light cylinders it was the smaller one that was lifted higher than the larger one . For the two heavy cylinders , it was the larger one that was lifted higher than the smaller one . The interaction between object mass and object size on lifting height -- reflecting the size -- weight illusion effect -- was most pronounced in repetition 1 as confirmed by the first-order interaction between object mass and repetition -LSB- F -LRB- 2,26 -RRB- = 123.8 , P < 0.001 -RSB- but remained present in repetitions 2 and 3 as reflected by the second-order interaction between object mass , object size and repetition -LSB- F -LRB- 2,26 -RRB- = 3.78 , P < 0.05 -RSB- , confirming the robustness of the size -- weight illusion . Fig. 3Means and standard errors of the lifting height -LRB- in cm -RRB- as a function of role -LRB- putting vs. fetching -RRB- , object diameter -LRB- small vs. large -RRB- and object weight -LRB- light vs. heavy -RRB- for repetitions 1 , 2 and 3 separatelyTable 1Results of repeated measures Anova on the lifting height according to a 2 role -LRB- putting vs. fetching -RRB- × 2 object mass -LRB- 230 vs. 835 g -RRB- × 2 object sizes -LRB- 2.5 vs. 6.5 cm in diameter -RRB- × 3 repetitions factorial designFactordfFPRole1 ,13 < 1NSObject mass1 ,1386.5 < 0.001 Object size1 ,137.1 < 0.05 Repetition2 ,2658.0 < 0.001 Role × object mass1 ,13 < 1NSRole × object size1 ,131.3 NSObject mass × object size1 ,1314.4 < 0.01 Role × object mass × object size1 ,13 < 1NSRole × repetition2 ,26 < 1NSObject mass × repetition2 ,26123.8 < 0.001 Role × object mass × repetition2 ,26 < 1NSObject size × repetition2 ,263.67 < 0.05 Role × object size × repetition2 ,26 < 1NSObject mass × object size × repetition2 ,263.78 < 0.05 Role × object mass × object size × repetition2 ,26 < 1NS No main effect or interaction of role -LRB- put vs. fetch -RRB- was found -LRB- all Fs < 1 -RRB- , which was not unexpected since cylinder-weight increases and decreases were expected to have counteracting effects on the lifting heights by the putter and fetcher if any interpersonal transfer would take place at all . Targeted paired t tests confirmed that there were systematic interpersonal transfer effects of lifting height between putter and fetcher as will be described next . A detailed time-series analysis of the lifting heights which the dyads realized indicated that the fetching-actor benefited from movement observation . The results of this analysis are shown in Fig. 4 . In those cases in which from one trial block to the next the cylinder 's weight changed from heavy to light and the putting-actor showed a ` surprise ' effect as reflected by an increase of her lifting height between these two trials of , on average , 4.69 cm , the fetching-actor showed a similar surprise effect but to a smaller extent . This reduced surprise effect in the fetching-actor of , on average , 3.67 cm , is shown in the left-hand graph of Fig. 4 . The incidence of this effect was relatively high . It happened in 88 % of those trials -LRB- i.e. , N = 99 -RRB- in which a heavy-to-light cylinder-weight change occurred . A two-tailed t test comparing the lifting heights on trial i − 1 and trial i -LRB- being the third trial of each trial block and the first of the subsequent block , respectively -RRB- for the putting-actor revealed that her surprise effect was statistically significant -LSB- t -LRB- 98 -RRB- = 15.98 , P < 0.01 -RSB- . For the fetching-actor , the smaller surprise-effect was also statistically significant -LSB- t -LRB- 98 -RRB- = 13.54 , P < 0.01 -RSB- . A repeated measures ANOVA confirmed that the relevant interaction between role -LRB- putter vs. fetcher -RRB- and trial -LRB- i − 1 = heavy and i = light -RRB- was statistically significant -LSB- F -LRB- 1,13 -RRB- = 7.24 , P < 0.05 -RSB- . Fig. 4Means and standard errors of the lifting height -LRB- in cm -RRB- of the putting-actor and the fetching-actor . Left-hand graph : whenever the putting-actor showed a lifting-height increase from trial i − 1 to trial i due to an unexpected mass reduction between these trials , the fetching-actor also showed this surprise effect but less strong . Trials i − 1 were the third trials of the trial blocks ; trials i were the first trials of the subsequent trial blocks . Right-hand graph : similarly , whenever the putting-actor showed a lifting-height decrease from trial i − 1 to trial i due to an unexpected mass increase between these trials , the fetching-actor also showed this surprise effect , but again , not as strong as the putting-actor did We found a similar effect when focusing on those trial pairs in which the cylinder-weight changed from light to heavy and the putter showed a ` surprise ' effect as reflected by a decrease of her lifting height between those trials . The results of this analysis are shown in the right-hand graph of Fig. 4 . Whereas the putting-actor proved to lift the cylinder , on average , 2.21 cm less high when the cylinder turned heavier from trial i − 1 to trial i , the fetching-actor did so as well but , on average , for only 0.97 cm . The incidence of this phenomenon was at chance level , i.e. , in 54 % -LRB- N = 61 -RRB- of the cases in which such a cylinder-weight change occurred in the experiment . A two-tailed t test comparing the lifting heights on trial i − 1 and trial i for the putting-actor and fetching-actor separately again revealed that the effects were statistically significant for both actors -LSB- t -LRB- 60 -RRB- = 12.08 , P < 0.01 , t -LRB- 60 -RRB- = 3.69 , P < 0.01 , respectively -RSB- . A repeated measures ANOVA confirmed that the relevant interaction between role -LRB- putter vs. fetcher -RRB- and trial -LRB- i − 1 = light and i = heavy -RRB- was statistically significant -LSB- F -LRB- 1,13 -RRB- = 31.08 , P < 0.001 -RSB- . The time-series analyses on light-to-heavy cylinder weight changes and vice versa were corroborated by the results of dyad-based linear regression analyses in which the lifting height of the putting-actor in the first trial of the trial blocks was used as predictor for that of the fetching-actor . In contrast to the repeated measures ANOVA , the regression analysis took into account lifting-height co-variations in both directions , i.e. , increases as well as decreases . An example of these data is depicted in Fig. 5 . The slopes of the resulting regression equations turned out to be smaller than 1.0 for all 14 dyads showing that the putting-actor was more surprised by a cylinder-weight change than the fetching-actor . For nine of the dyads the positive slope proved statistically significant -LRB- P < 0.05 -RRB- . On average , the slopes amounted to 0.43 -LRB- R2 = 0.25 -RRB- , indicating that the fetching-actors were less surprised by any cylinder-weight change than the putting-actors . Fig. 5Example of the linear regression analysis between the lifting-height data generated by the putter and fetcher of 1 of the 14 dyads participating in the study . The data concern the first trial within trial blocks of three repetitions of the experimental conditions . The regression analyses revealed the robustness of the observed reduction of the size -- weight illusion due to movement observation in the dyads studied . The dashed line with slope = 1 represents the situation in which the lifting height of the fetcher would equal that of the putter Effects of target-area size variations Figure 6 shows the average effects on the mean tangential wrist velocity of the putting and fetching-actors as a function of the manipulations of the size of the target regions where the cylinders had to be placed . The second part of the sequential action under study , i.e. , fetching the cylinder from the middle of the table , proved for no apparent reason overall to be performed somewhat slower than the first part , i.e. , putting the cylinder in the middle of the table . The performance speeds of the participants were independently tuned to the sizes of the target areas with which the actors were confronted . In line with Fitts ' law , small target areas elicited low speeds and large ones yielded high speeds . This relationship applied to both actors whether or not they were confronted with similar or dissimilar accuracy constraints . Table 2 summarizes the repeated measures ANOVA to evaluate these effects with a 2 roles -LRB- put vs. fetch -RRB- × 2 sizes of putting target region -LRB- ` putting-size ' ; small vs. large -RRB- × 2 sizes of fetching target region -LRB- ` fetching-size ' ; small vs. large -RRB- factorial design . The absence of the first-order interaction between putting-size and fetching-size -LRB- F < 1 -RRB- and the second-order interaction between the factors role , putting-size and fetching-size confirm the robustness of these findings . Fig. 6Means and standard errors of the mean wrist speed -LRB- in cm/s -RRB- as a function of role -LRB- putting vs. fetching -RRB- and target area size -LRB- S = Small , L = Large ; p = put , f = fetch -RRB- . The labels with subscript p reflect the size of the target area of the putting-actor and labels with subscript f reflect the size of the target area of the fetching-actorTable 2Results of repeated measures ANOVA on the mean wrist speed -LRB- in cm/s -RRB- according to a 2 role -LRB- putting vs. fetching -RRB- × 2 putting-size -LRB- small vs. large target area -RRB- × 2 fetching-size -LRB- small vs. large target area -RRB- factorial designFactordfFPRole1 ,1318.60 < 0.01Putting-size1 ,1375.07 < 0.001Fetching-size1 ,1333.90 < 0.001 Role × putting-size1 ,1320.21 < 0.001 Role × fetching-size1 ,1322.03 < 0.001Putting-size × fetching-size1 ,13 < 1NSRole × putting-size × fetching-size1 ,13 < 1NS A trial-by-trial inspection of the speed changes of both actors revealed , however , a moderate degree of performance-speed adaptation by the fetching-actor to that of the putting-actor . Figure 7 shows the results of this analysis . If from one trial to the next the size of the target areas remained constant for both actors but the putting-actor increased her performance speed for some reason , the fetching-actor followed this incidental speed increase of the putting-actor only partially as shown in the left-hand graph of Fig. 7 . The incidence of this co-variation in performance speed between the two actors was below chance level , i.e. , it happened in 34 % -LRB- N = 150 -RRB- of the cases in which the phenomenon could theoretically occur . Nevertheless , the changes in speed were , in both actors , statistically significant -LSB- t -LRB- 149 = 7.63 , P < 0.02 and t -LRB- 149 -RRB- = 5.95 , P < 0.01 , two-tailed , for the putting-actor and fetching-actor , respectively -RRB- . Fig. 7Means and standard errors of the wrist speed -LRB- in cm/s -RRB- of the putting-actor and the fetching-actor . Left-hand graph : whenever the putting-actor showed a task-unrelated speed increase from trial i − 1 to trial i , the fetching-actor also showed such a speed increase . The trials involved concerned the second and third trials of the trial blocks in which no task conditions changed . Right-hand graph : similarly , whenever the putting-actor showed a task-unrelated speed decrease from trial i − 1 to trial i , the fetching-actor followed this speed decrease The reverse co-variation of performance speeds happened slightly more often . The right-hand graph of Fig. 7 shows that whenever the putting-actor reduced her movement speed from trial i - 1 to trial i during which the size of the target regions remained constant , the fetching-actor again partially followed this speed decrease . This co-variation in speed occurred in 42 % -LRB- N = 186 -RRB- of the cases in which this effect could occur . For the putting-actor and fetching-actor the speed decreases that were isolated here were again both statistically significant -LSB- t -LRB- 185 -RRB- = 5.95 , P < 0.01 and t -LRB- 185 -RRB- = 3.32 , P < 0.01 , two-tailed , respectively -RSB- . Linear regression analyses in which the mean wrist speeds of the putting-actor as observed in the second and third trials of the trial blocks were used as predictor for that of the fetching-actor confirmed the just described results . The slopes of the regression equations proved positive for 12 of the 14 dyads indicating that the fetching-actor followed the speed changes of the putting-actor in direction but only partially in size . For 10 of the 14 dyads the positive correlations proved statistically significant -LRB- P < .05 -RRB- . R2s in these analyses ranged between 0 and 0.33 -LRB- mean R2 was 0.11 -RRB- indicating the target-size independent speed relationship between the two actors was weak . Combined effects of size -- weight illusion and speed-accuracy trade-off An inspection of the combined effects of the three task constraints that were manipulated revealed that even though on average the heavier cylinders were transported at a systematically lower speed than the lighter cylinders -LRB- mean = 43.78 cm/s ; SD = 8.37 cm/s for the light cylinders and M = 38.14 cm/s ; SD = 7.06 cm/s for the heavy cylinders -RRB- , the speed variations due to the variations in the size and weight of the cylinders did not differentially affect the movement-speed variations as a result of the target-area size variations . Lifting-height variations due to the spatial accuracy-constraint manipulations were marginal -LRB- < 2 mm -RRB- and also did not systematically influence the lifting-height variations due to the size-illusion effect . Discussion The present study examined the extent to which at the level of movement kinematics a transfer of performance parameters takes place between co-actors involved in transferring objects . The results of the main analyses that we conducted to assess the effect sizes of the experimental manipulations were largely negative . Object-mass variations induced lifting-height variations of equal size in both actors . Target-region size based speed variations also did not show interpersonal transfer . These results suggest that in sequential joint actions the tuning to each others movement parameters is absent and thus demonstrate the limits of automatic movement simulation by observation as suggested by mirror-neuron theories -LRB- Gallese and Goldman 1998 ; Gallese et al. 2004 ; Rizzolatti and Craighero 2004 -RRB- . However , it remains to be seen whether the mirror-neuron system represents observed actions with a precision that allows for direct imitation . This does not appear to be the case in macaque monkeys . One could claim that any hypothetical system in general could infer the goals/intentions of observed movements without explicitly representing , say , the speed of the movement . More detailed analyses of incidental interpersonal transfer effects indicated that the situation was more complex than that . When focusing on the effects of between-trial cylinder-weight changes , the actor who was confronted with such changes first showed a systematically larger surprise-effect than the actor who was asked to transport the cylinder after the first actor had done so . A key finding here was that through the realized trajectory height during object transportation , the object mass was picked up by movement observation and integrated into the observer 's movement plan . Our prediction was therefore confirmed , i.e. , the movements of an actor are likely to affect a subsequent , complementary movement generated by an observer . Regarding the size of the effects it proved that the object property mass was , via lifting height , a more prominent factor determining task performance of the co-actors than movement speed . The linear regression analyses of the between-trial lifting-height changes due to cylinder-mass changes yielded larger proportions of explained variance when correlating the behavior of the fetching-actor with that of the putting-actor than the comparable analyses involving the incidental speed changes . With respect to goals and means of task performance , the dominance of object-mass over target-width makes sense given that the object is more likely to function as a goal in the task of handing over objects than the movements needed to perform such a task -LRB- Cuijpers et al. 2006 -RRB- . In a similar vein , the different sizes of the effects of object mass and movement speed could be taken to provide support for the importance of goal-inference making in collaborative joint action over and above a quasi-automatic , direct-matching based process of movement imitation or ` motor resonance ' -LRB- Flanagan and Johansson 2003 ; Iacoboni et al. 1999 ; Koski et al. 2003 -RRB- -LRB- Fig. 8 -RRB- . Fig. 8Example of the linear regression analysis between the wrist-speed data generated by the putter and fetcher of 1 of the 14 dyads participating in the study . The data concern the second and third trials within trial blocks of three repetitions of the experimental conditions . The regression analyzes revealed the robustness of the observed , task-constraint independent covariation of movement speed between the two actors . The dashed line with slope = 1 represents the situation in which the wrist speed of the fetcher would equal that of the putter Our interpretation of the current results does rely , of course , on the validity of both the weight-change effects and the co-variation of the actors ' movement speeds . It could be argued that the fetcher 's movement speed covaried with that of the putter due to a non-specific , visually primed increase in attention rather than the direct consequence of perceiving the putter 's object-transportation movements . However , attentional mechanisms are an unlikely explanation for our observations since the only visual cue that could have increased the attention in the fetcher was the putter 's movement speed . Whether the object-weight related adaptation in the fetcher to the observed movement of the putter was due to the inference of the weight of the object or to the observed kinematics per se , also remains a matter of discussion . If it was the former , then motor resonance -LRB- i.e. , mirror-neuron system -RRB- may not be responsible for a direct transfer of the kinematics parameters . The effects of the object and the accuracy constraints differ in one fundamental aspect . The expected information transfer for the object is valid for the programming of the movement , while any hypothesized transfer of speed , by simple copying the observed movement to reduce dimensionality violates Fitts ' law . This implies that our hypothesis about the transfer of speed was either not valid or that the effect is intrinsically short lived because the duration of the effect is overruled by intrapersonal constraints . In other words , while the information about weight change is very relevant for movement programming , the examined speed changes were not . Apparently , movements that are being observed in a joint-action task can be used for multiple purposes . First , the observation might lead to internal simulation in order to understand the behavior that is being observed -LRB- Rizzolatti and Craighero 2004 -RRB- . Second , the internally simulated movements might provide clues as to the intentions associated with the observed behavior -LRB- Oztop et al. 2005 ; Wolpert et al. 2003 ; Iacoboni et al. 2005 -RRB- . Third , the observed movements might form the basis for prediction as to what an actor might do in the near future -LRB- Csibra 2005 -RRB- . Fourth , observed movements might provide clues about the task constraints at hand . In the present experiment , lifting height was such a parameter that indicated to the observer the weight of the cylinder that was transported . Fifth , observed movements may provide a global scaling parameter of ones own future actions , specifically if these actions are complementary to those performed by the actor that is being observed . Further research into the factors that determine the relative importance of these various roles which action observation may play in joint action is clearly needed . Our study also suggests that kinematic parameters picked up during movement observation may even affect a subsequent movement that is performed in a workspace that is totally differently oriented than the workspace of the actor being observed . This finding extends the findings of the recent study by Van Schie et al. -LRB- 2004 -RRB- who showed that action observation activates cortical motor areas as if the observer had performed the task herself , i.e. , when an observer who is facing an actor sees that actor move with her right hand the right cortical motor areas of the observer become activated indicating that the observer would have executed the task with her left hand . These findings suggest that movement simulation is egocentric and viewpoint-dependent . Our demonstration of interpersonal action coordination in complementary joint action was restricted to the successive transportation of a cylinder by two actors . The movements preceding and succeeding the actual transportation of the cylinder could also have been scrutinized for signs of action coordination . However , the amplitudes of these movements by the two actors were hardly comparable . Moreover , the dyads involved in this study showed , not surprisingly , also the tendency to wanting to start task performance simultaneously . The preference of people to adopt either in-phase or out-of-phase timing patterns is not only prevalent in individual , inter-limb coordination tasks but also when people perform tasks together -LRB- Schmidt and O'Brien 1997 ; Shockley et al. 2003 -RRB- . These tendencies clearly co-exist alongside the casual transfer of kinematic movement parameters in dyadic action sequences .

O B O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B I O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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