Schedonorus pratensis) in response to medium intensity (corresponding with densities of ca. 1200 voles/ha for 5 weeks during 3 months) or heavy intensity (ca. 1200 voles/ha for 8 weeks during 3 months) grazing by a mammalian herbivore, the field vole (Microtus agrestis). A laboratory experiment was then conducted to evaluate the effects of endophyte infection status and grazing history of the grass diet on vole performance. As predicted, grazing increased foliar silicon content, by up to 13%. Grazing also increased foliar levels of phosphorous and several phenolic compounds, most notably those of the flavonols isorhamnetin-diglycoside and rhamnetin derivative. Silicon concentrations were consistently circa 16% higher in E+ grasses than in E-grasses, at all levels of grazing. Similarly, concentrations of chlorogenic acid derivative were found to be consistently higher in E+ than in E- grasses. Female voles maintained on heavily grazed grasses suffered higher mortality rates in the laboratory than female voles fed ungrazed grass, regardless of endophyte infection status. Our results conclusively demonstrate that, in addition to tolerance, grasses employ multi-tiered, effective defenses against mammalian grazers.Grasses have been considered to primarily employ tolerance in lieu of defense in mitigating damage caused by herbivory. Yet a number of mechanisms have been identified in grasses, which may deter feeding by grazers. These include enhanced silicon uptake, hosting of toxin-producing endophytic fungi and induction of secondary metabolites. While these mechanisms have been individually studied, their synergistic responses to grazing, as well as their effects on grazers, are poorly known. A field experiment was carried out in 5 × 5 m outdoor enclosures to quantify phytochemical changes of either endophyte-infected (E+) or endophyte-free (E-) meadow fescue ( Grasses are highly tolerant to grazing by means of their rapid regrowth capacity, basal meristems, underground storage organs and tillering capacity . Indeed,Following herbivore damage, Si is drawn from the soil and deposited systemically in the cell walls or lumina of new shoots as silica bodies or phytoliths . These fGrazers have often been observed to avoid plant material with high Si content . HoweverMany grass species harbor systemic, vertically transmitted endophytic fungi, which may also increase the resistance of the host to herbivory , 2006. EWhile adverse effects of endophyte consumption are well documented for domestic livestock , which is commonly infected by the endophytic fungus Epichloë uncinata (Microtus agrestis served as our model grazing herbivore.Meadow fescue (uncinata  was useduncinata  known touncinata . A commoThe following specific hypotheses were tested: (1) vole grazing elevates levels of both Si and phenolics in grasses, (2) the magnitude of response of Si and phenolics to grazing differs between endophyte-infected and non-infected grasses, and (3) consumption of heavily grazed grass, as compared to consumption of less heavily grazed grasses, has negative impacts on vole physiological condition, and more so if the grass is endophyte-infected.E. uncinata, which produces loline alkaloids, which appear to be non-toxic to large mammal herbivores  were established in May 2006 in an old agricultural field by tilling, fertilizing with cow manure (30 000 kg/ha) and sowing as monocultures either endophyte-free seed lots  or endophyte-infected seed lots  of the meadow fescue cultivar “Kasper” at a rate of 20 kg ha-1  during summer 2011. The enclosures  in order to retain the experimental voles and exclude voles of natural populations and small mammal predators.Figure 1). Four 5m × 5 m sheet metal plots arranged in 2 × 2 squares were constructed  in one randomly assigned corner (corners bordering the outside of the enclosure complex were excluded to reduce predator attraction) of each of the 10 enclosures (5 × E+ and 5 × E-). Two plots per enclosure were randomly designated as vole grazing plots (G+) and two as non-grazed control plots (G-).Every second enclosure pair of the 10 available pairs was selected for the experiment , vole grazing in endophyte-free plots (G+E-), no grazing in endophyte-infected plots (G-E+), and no grazing in endophyte-free plots (G-E-). The grazing treatment was begun in late May 2011 by introducing two adult field voles, trapped in the vicinity of the enclosures and in Suonenjoki, Eastern Finland, into each G+ plot. Prior to introduction, all voles were housed in standard laboratory rodent cages  with ad libitum water, feed pellets , and turnip.Two levels of grazing intensity we applied to ensure adequate responses of grasses to the grazing treatment. The medium grazing intensity treatment involved two voles grazing in each plot continuously for 2 weeks, and thereafter four voles grazing for 3 weeks, either directly after the first 2 weeks, or after a 3 week period of no grazing. The heavy grazing intensity treatment involved two voles grazing in each plot continuously for 2 weeks, and thereafter four voles grazing first for 3 weeks, followed by 3 weeks of no grazing and finally another 3 weeks of grazing by four voles.In summary, the medium grazing intensity plots received 14 days of grazing at a vole density corresponding to 800 voles / ha (2 voles × 0.0025 ha = 800 voles/ha) plus 21 days of grazing at a vole density corresponding with 1600 voles/ha (4 voles × 0.0025 ha = 1600 voles/ha). The high intensity grazing treatments received 14 days of grazing at 800 voles / ha plus 42 days of grazing at 1600 voles/ha. The collective grazing intensity over the experiment approximated 1200 voles/ha for 5 weeks during 3 months and ca. 1200 voles / ha for 8 weeks during 3 months for the medium and heavy grazing intensity treatments, respectively. The level of grazing on individual grasses was not measured, but visual inspection indicated that while heavy grazing did have a substantial effect on vegetation, grasses were at no point during the experiment entirely deplete within the plots.Live trapping was conducted in mid-June in all enclosures to measure the body mass of voles in the G+ enclosures and to verify that no voles had entered the G- enclosures. As expected, no voles were encountered in the G- enclosures. However, only circa 25% of the originally introduced voles were trapped in the G+ enclosures over three nights. This strongly indicated predation within the experimental enclosures, and a cat was occasionally seen around the enclosure complex.Therefore, the experimental grazing protocol was altered from its original form. In mid-June, all voles were removed from the plots. Four field voles were then introduced into half of the G+ plots for a period of 3 weeks. Thereafter, the voles were trapped and translocated to the remaining plots. This was again repeated after 3 weeks, with four voles returned to the plots that were first grazed. During this 9 week period, only seven voles disappeared, and those that did were replaced upon translocation. All voles were live trapped out of the plots at the end of August.To evaluate the effects of grazing on phytochemistry, meadow fescue samples were collected in each of the plots three times during the summer: immediately prior to introduction of voles, once at the beginning of August and once at the beginning of September (1 week after voles had been removed). Each time, one tiller was removed at the base from three randomly selected meadow fescue plants per plot and pooled into one sample. During the first sampling occasion, samples from the two G+ and two G- plots per enclosure were also pooled.The Si, phosphorous (P), nitrogen (N), and carbon (C) contents of the samples were analyzed for each of the three sampling occasions. For these analyses, grass samples were washed under water, oven dried at 80°C and ground into a fine, non-fibrous powder. Three hundred milligram of this powder was pressed in a hydraulic press into a 3 mm thick, 13 mm diameter pellet with a pressure of 13 bar. Si and P content (expressed as percentage dry weight) was analyzed from the pellets with a portable X-ray fluorescence spectrometer , as described by Phenolic compounds were analyzed only from samples collected on the last occasion, after the grazing treatment. These samples were air dried at room temperature for 1 week prior to analyses. All soluble non-tannin phenolic compounds were extracted and HPLC-analyzed from the grass leaf samples according to the protocol described in n = 24 voles per treatment group), which received ad libitum grass collected daily from the experimental plots . For this segment of the study, all grass collected from grazed enclosures was pooled and not distinguished between heavy or medium grazing. Voles also received pieces of potato for extra hydration.At the beginning of September, a laboratory experiment was carried out to evaluate how earlier grazing and endophyte infection status affected vole physiological condition and performance. 96 wild field voles, captured near the towns of Suonenjoki, central Finland  and Jokioinen, were housed in same sex pairs in a decommissioned greenhouse, in standard laboratory cages containing peat and straw as bedding and nest material. The voles were assigned to one of four food treatment groups  every 3–4 days . In the beginning and at the end of the feeding period, a blood sample was collected from the retro-orbital sinus of each vole using a capillary tube. Tubes were then centrifuged at 12000 g for five minutes, and haematocrit expressed as the percentage of packed red blood cells in total volume. The feeding experiment was terminated and all voles euthanized due to an increased rate of mortality in the end of the second experimental week, for reasons that remain unidentified.The experiment was carried out under permit from the Animal Ethics Council of the State Provincial Office of Southern Finland.Variation in grass Si, P, N, and C content was analyzed with linear mixed models using the maximum likelihood method, where each of the elements was in turn the response variable. Grazing intensity , endophyte infection status (E+ or E-), time  and all interactions were initially entered in the models as class explanatory variables. Time was designated a repeated factor, with plot as the subject. In all cases, AIC-based model selection  indicatee -transformed. Grazing intensity, endophyte infection status and their interaction were entered as fixed explanatory variables, while enclosure and plot (nested within enclosure) were designated random factors.Variation in phenolics concentrations at the end of summer was also analyzed with separate linear mixed models for each compound using the maximum likelihood method. Initially, all peak intensity values for the different compounds were logThe overall response of meadow fescue to the treatments in terms of their phenolic content was also analyzed with multivariate analysis of variance using all 16 identified phenolic compounds as response variables, and grazing intensity, endophyte infection status and their interaction as explanatory variables.Changes in the body mass and haematocrit value of voles that survived to the end of the laboratory experiment were analyzed with linear mixed models, with the percentage of change relative to the beginning of the experiment as the response variable. Grazing history (grazed or not) and endophyte infection status of the grass they were fed, vole sex and body mass at the beginning of the experiment, together with all possible three-way interactions, were entered as fixed explanatory variables. Identity of the cage in which the voles were housed was entered as a random factor. Full models were reduced by removing explanatory terms on the basis of AIC. Model fit was assessed by visual observation of the final model residuals.Vole survival during the laboratory experiment was analyzed with generalized linear mixed models, using vole survival as a binary response variable with a logit link. Grazing history and endophyte infection status of the grass, vole sex, and all interactions, were entered as fixed explanatory variables and vole cage as a random factor.® Institute Inc., Cary, NC, USA).Full models were reduced in all analyses by removing explanatory terms on the basis of AIC – terms were removed if this reduced the AIC value by >2 units . Model fF2,24.4 = 3.50, p = 0.046). Highest levels were recorded in the heavy grazing treatment (mean ± SE. Si content as percentage dry weight = 1.56 ± 0.07%), followed by medium grazing (1.54 ± 0.08%), while control grasses had the lowest values . Si levels were consistently higher in E+ grasses than in E- grasses, with no significant interactive effect of grazing .Grazing elevated the Si content of grasses . Highest levels were recorded in the medium grazing treatment (mean ± SE. P content as percentage dry weight = 0.42 ± 0.01%), followed by heavy grazing (0.42 ± 0.01%), while control grasses had the lowest values . The level of P declined in E+ grasses over the summer, whereas that in E- grasses remained stable . No differences were found in concentrations of N, C, or in C/N-ratio relative to grazing intensity, endophyte infection status, time or their interactions .Likewise, grazing elevated the P content of grasses . One-way multivariate tests with either E+ or E- samples did not clearly indicate which of the main effects had a stronger effect on grass phytochemistry. The varying degrees of grazing intensity tended to influence the phenolics profile of endophyte-free samples , but these differences were less pronounced in endophyte-infected samples .A two-way multivariate analysis of variance revealed a significant interaction between grazing intensity and endophyte infection status on the phenolics profile of the grasses . Concentrations of chlorogenic acid derivative were higher in E+ than in E- grasses. Two compounds were affected by the interaction between grazing intensity and endophyte status. Levels of quercitrin, in particular, were positively associated with grazing intensity, but only in E+ grasses (Table 1).Five of the 16 analyzed phenolic compounds exhibited an elevated response to grazing – chlorogenic acid, isorhamnetin-diglycoside, myricetin-glycoside, isorhamnetin 3-glucoside, and rhamnetin derivative .The body mass of voles maintained in the laboratory on endophyte-infected and endophyte-free grasses responded differently to the grazing history of their diet. Voles feeding on endophyte-free grass that had been grazed throughout the summer lost relatively more mass than voles in the other three groups . Feeding on previously grazed grass also had a significant negative main effect on vole body mass change . Females lost more body mass than males, irrespective of dietary group . Conversely, females maintained on heavily grazed grasses suffered ca. 45% higher mortality rates than females fed ungrazed grass, regardless of endophyte infection status; these differences did not manifest in males .Females that had fed on endophyte-infected grass had elevated haematocrit levels compared to those fed on endophyte-free grasses . Many phenolics are inducible defensive compounds, which either inhibit digestion by herbivores, are deterrent or even directly toxic . Quercitrin consumption has been shown to reduce the growth of weanling voles, and most profoundly so when dietary protein levels are low , in particular, were positively associated with grazing intensity, but only in E+ grasses ( are low . The eff are low .The grazing-induced elevation of Si may have more far-reaching effects than the up-regulation of the physical defense of plants. For example, Si appears also to have a functional role in the systemic response of plants to pathogens, through the activation of general defensive pathways, e.g., involving salicylic, or jasmonic acids . ElevateA caveat of our study is that we were unable to determine the effects of vole grazing on either the amount of endophyte hyphae per grass leaf or the concentrations of mycotoxin alkaloids that the fungus produces. Voles that consumed previously grazed grass lost body mass in the laboratory. Females, in particular, suffered mass loss while maintained in the laboratory, regardless of treatment. The voles were offered only one species of grass as diet. Consumption of such a monotonous diet is highly unlikely for voles in natural habitats . The facFemales that had fed on endophyte-infected grass had elevated haematocrit levels compared to those fed on endophyte-free grasses. Haematocrit measures the relative volume of red blood cells in whole blood, and its values may increase due to either proliferation of red blood cells, or, more commonly, due to a reduction in blood plasma content due to dehydration . A dehydHighest levels of mortality were recorded for females maintained on grazed grasses. Conversely, endophyte infection status did not affect mortality rates. Although endophyte infection status appeared to be associated with female food avoidance in the laboratory, as judged by hematocrit levels, these effects were not pronounced enough to impact survival. Collectively, our results indicate that grazing-induced changes in the quality of diet, i.e., increased Si and phenolics content, outweigh the potential negative effects of endophyte infection on the physiological condition of voles see . FurtherOur results render support to the hypothesis that food quality may indeed have a limiting effect on vole population growth, in cases when grazing is severe and long enough see . We concThe 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.


We introduced video-based teaching in pediatrics. We evaluated the impact of a pediatric video program on student performance in assessing pediatric patients presented as video cases. The program consisted of a library of pediatric videos, and inclusion of these in the teaching and examination for pediatric medicine.Medical students on a pediatric clerkship at the University of Copenhagen assessed eight short pediatric video cases during autumn 2011 and spring 2012. Two independent observers evaluated a subset of records in a pilot study. A blind evaluation was made of the written records of 37 students before, and 58 students after, the introduction of the program using a Rubric score with four domains.The intraobserver interclass correlation coefficient was 0.94 and the interobserver interclass correlation was 0.71(n=25). The students’ mean total Rubric score in spring 2012 (7.0) was significantly higher  than autumn 2011 (4.7). Cohen's d was 1.1 (95% CI 0.6–1.7). Single domains scores increased significantly for general assessment (1.30 versus 0.57) , recognition of principal symptoms (1.38 versus 0.81) , appropriate diagnosis (2.28 versus 1.78)  and consistency between observed symptoms and diagnosis (1.94 versus 1.57) .Students improved in evaluating pediatric patients presented as video cases after the introduction of the program. The impact on real-life situations remains to be established. The clinical assessment of pediatric patients is difficult, and students' access to pediatric patients may also be limited because of seasonal variation and short clerkships. This is likely to limit the acquisition of competence . TeachinDual-code theory states that the formation of mental images aids learning . InclusiEducators have explored the efficacy of using patient video cases, which, at least in theory, expose students to the complexity of actual clinical problems . AlthougThe aim of this study was to evaluate the effect of a video case teaching program in Pediatrics on students’ performances in assessing pediatric patients presented as video cases.Before January 2012, standard education in Pediatrics at the University of Copenhagen consisted of a 5-week pediatric clerkship. During the clerkship, students participated in daily activities at the pediatric departments as well as problem-based learning sessions and formal lectures. The clerkship ended with a 30-minute oral assessment, based on a written patient case.In January 2012 (spring semester 2012), a video case teaching program in Pediatrics was introduced. This consisted of access to a new library of 180–200 short pediatric patient video cases on the university e-learning platform, which was available online 24/7 to medical students during their pediatric clerkship. We have previously described the content of and topics covered by the video case library . AccordiIn a prospective study design, medical students who attended the pediatric course at the University of Copenhagen during autumn 2011 and spring 2012 semesters participated in a test, where students assessed eight video cases presenting different common conditions in pediatric patients  completed the test to evaluate the effect of the program. The groups had a comparable mean age (28.3 years in autumn 2011 and 28.5 years in spring 2012) and gender balance .The student mean total Rubric score in spring 2012 was significantly higher (7.0) than the students’ total score in autumn 2011 (4.7)   , assessment of principal symptoms (1.38 versus 0.81)  and diagnoses (2.28 versus 1.78) . Improvement in consistency between description, symptoms, and diagnosis just reached the level of significance (1.94 versus 1.57) .As described previously , studentIn our study, students’ abilities to evaluate pediatric patients presented as video cases, as assessed by a Rubric score, significantly improved after the introduction of the video case teaching program. The data are robust, as the intra- and interobserver interclass correlation coefficients were very good, even though more independent observers would have provided further strength.Using clinical video cases of pediatric patients in an authentic clinical context, rather than single text cases with or without still pictures, may enable students to work on developing observational skills, which otherwise develop haphazardly with clinical experience.As the program was in several parts, our study does not give a clear picture of the causes of the observed increase in students’ Rubric scores. It is well known that students focus their attention on what will enable them to pass examinations -11. ThisAnother limitation of our study is the relatively small number of students. As the composition of the Rubric will naturally influence the outcome, the choice of domains and standards for Rubric scores may also be worthy of discussion, as different choices and sets of standards might have altered the results. The Rubric score was not tested on any selection of video cases other than the eight used in this study. Our Rubric score therefore needs further evaluation to clarify its usefulness in evaluating student performance in assessing pediatric patient video cases. Supplementary focus group interviews would have provided further information about the mechanisms involved in the students’ cognitive processes when assessing the video cases.We were surprised that many reports demonstrated little consistency, as some students described symptoms other than those the child presented, but somehow managed to make an appropriate diagnosis, or described the symptoms well but gave an entirely irrelevant diagnosis. An example from several students was the correct description of inspiratory stridor and croupal cough in video case no. 1, a child with croup, but a diagnosis of asthma or pneumonia. From the dual-code theories, the observed discrepancy may demonstrate that the students did not integrate the visual cues in the video cases with their theoretical knowledge of pediatric symptoms and illness. We speculate that this could be improved by increasing the number of supervised video tutorials, or by including more videos in the diagnosis-focused teaching sessions.We also noted a tendency for the students to overlook and fail to report on the general appearance of the child. We speculate that this may be due to “tacit knowledge”—that students may not pay attention to, or may unconsciously assess, the general condition of the child, and focus on symptoms and diagnosis. This interpretation is supported by our unstructured observation of the apparently intuitive ability of students, even on the first days in clerkship, to identify a “normal” rather than severely ill child.Other studies ,12-19 thSeveral studies have shown that authenticity—that is, a realistic situation and the feeling of “caring for a real patient"—is the critical feature of a video case and contributes to higher learning by enhancing case discussions ,13. The Kamin et al.  comparedIn another study investigating the influence of video cases compared with written cases on the critical thinking process in problem-based learning, Kamin et al.  showed tBalslev et al.  comparedThe students in our study commented very positively on the use of video cases, but also expressed their need for supervision and dialogue as a critical way to achieve effective learning from the use of video cases. This is in accordance with other studies -18,21,22Kamin et al.  investigFinally, and importantly, we have not been able to find studies that have shown a beneficial effect of patient video case-based learning on the clinical assessment of patients in real life. Further studies are needed.The availability of a formal video case teaching program was very effective in improving student ability to assess such video cases. It remains to be established if these interventions also improve their ability to assess patients in real-life situations.The study was approved by the Danish Data Protection Agency, j.nr 2007-58-0015. Informed consent was obtained from all participants. All patient video cases were recorded with written informed consent from custody holders. The Danish Regional Health Research Ethics Committee was consulted, but no further approval was needed, as the study did not involve any kind of human intervention, excision of human tissue, or similar.


Parents who opted for early infant male circumcision (EIMC) and health care workers felt EIMC was a safe and acceptable procedure that would likely become more widely adopted over time. Barriers to EIMC uptake such as parental fears of harm and cultural beliefs are potentially surmountable with adequate education and support. Parents who opted for early infant male circumcision (EIMC) and health care workers felt EIMC was a safe and acceptable procedure that would likely become more widely adopted over time. Barriers to EIMC uptake such as parental fears of harm and cultural beliefs are potentially surmountable with adequate education and support. The World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) recommend early infant male circumcision (EIMC) for prevention of HIV. Here, we present findings from a qualitative study in Zimbabwe that assessed parental and health care workers' perspectives of EIMC conducted using devices.This qualitative study was nested within a trial of EIMC devices. Between January and May 2013, we held 4 focus group discussions (FGDs) and 12 in-depth interviews with parents and 12 in-depth interviews with clinicians . We also conducted 95 short telephone interviews with parents who had arranged to bring their sons for EIMC but then defaulted.Parents who had adopted EIMC spoke of their initial anxieties about the procedure. Additionally, they commented on both the procedure and outcome. Parents who decided against EIMC cited fear of harm, specifically the infant's death, penile injury, and excessive pain. Misperceptions about male circumcision in general and EIMC specifically were a significant barrier to EIMC adoption and were prevalent among health care workers as well as parents. In particular, the findings suggest strong parental concerns about the fate of the discarded foreskin. Parents who chose EIMC for their newborn sons felt that the procedure was safe and expressed satisfaction with the outcome. For their part, health care workers largely thought that EIMC was safe and that the outcome was aesthetically pleasing. They also felt that it would be feasible to offer wide-scale EIMC for HIV prevention in the public sector; they recommended strategies to increase EIMC uptake, in addition to highlighting a few concerns.The qualitative study enables us to better understand parental and health care workers' perspectives of EIMC conducted using devices, especially their perspectives on EIMC safety, feasibility, acceptability, and barriers. These findings will be used to design demand-generation activities that support wider adoption of EIMC. The program aims to reach 1.3 million 15- to 29-year-olds by 2017.,,,This qualitative study sought to complement an earlier study that explored the hypothetical feasibility and acceptability of EIMC among health care workers, parents, and the wider family  held in-depth interviews and focus group discussions (FGDs) with parents. Budgetary and time constraints limited the numbers of interviews, discussions, and phone calls. In all, 24 participants took part in in-depth interviews and another 38 in FGDs. An additional 95 parents took part in short phone interviews. No one declined to take part in the qualitative study.We conducted in-depth interviews and FGDs with parents who had adopted EIMC for HIV prevention—3 interviews and 1 FGD with a total of 10 mothers; 3 interviews and 1 FGD with a total of 9 fathers. We selected these participants randomly from a list of parents who had adopted EIMC. We also conducted interviews and FGDs with parents who had declined to circumcise their newborn sons—3 interviews and 1 FGD with a total of 10 mothers, and 3 interviews and 1 FGD with a total of 9 fathers. We selected these participants randomly from a list of couples who had not adopted EIMC and had not been shortlisted for short phone interviews . Discussions with clinicians assessed actual acceptability of the procedure and obtained their views on the feasibility of offering wide-scale EIMC using either the AccuCirc device or Mogen clamp. Discussions also elicited clinicians’ perceptions of the safety of the procedure when conducted with either device.Further, we conducted 95 short phone interviews with parents who had arranged to bring their sons for EIMC but then defaulted. The phone interviews sought to ascertain only the parents’ reasons for not bringing the infant for the procedure. In these phone interviews, we included 15 of the 17 parents (88%) who had gone through all study screening procedures  but did not eventually enroll. Of these 15, 10 were mothers and 5 were fathers. We selected the other 80 phone interview participants as follows: 65 women (10%) were randomly selected from a list of 650 mothers who had arranged to bring their sons for EIMC but then defaulted. An additional 15 men (10%) were randomly selected from a list of 150 fathers who had participated in weekend group meetings and had promised to bring their sons for EIMC but then defaulted . We contFGDs lasted 2 to 2.5 hours; in-depth interviews lasted 45 minutes to 1 hour. All FGDs were conducted in Shona, the participants’ language. In-depth interviews were conducted in either English or Shona, depending on the participant’s preference. We audio-recorded all FGDs and in-depth interviews.We transcribed the recorded interviews and discussions and, where necessary, translated them verbatim into English. We identified initial themes during the interviews and discussions; these themes informed an initial coding framework. Then, 3 researchers used this framework to code 5 in-depth interviews and all FGDs line by line on paper. This led us to add additional codes to the coding framework. We entered the transcripts into NVivo 10 , a qualitative data storage and retrieval computer program. Trained and experienced researchers (authors CM and SF) coded each transcription separately, using the modified coding framework, taking note of any emerging new codes. If the coders disagreed over the interpretation of some codes, the senior social scientist (WM) met with the 2 researchers. The 3 would examine the codes and collectively agree on the standard forms to use for coding. We then revised the coding framework accordingly. WM checked concordance of the 2 researchers’ coding in addition to independently coding all transcripts. We typed the handwritten statements from the phone interviews and entered the information into a Microsoft Excel document. Researchers read the statements and assigned each statement a code based on its key words.,We grouped codes into categories and then identified emerging themes following the principles of thematic analysis.The study was approved by the Medical Research Council of Zimbabwe and the ethics committees of University College London and the London School of Hygiene and Tropical Medicine. We obtained written informed consent from participants on the day of the interview or discussion. At the start of each short phone interview, we sought verbal consent.Parents who had adopted EIMC spoke about their initial anxieties concerning the procedure. Additionally, they commented on both the procedure and its outcome. Parents who had decided against EIMC mentioned fear of harm, specifically the infant’s death, penile injury, and excessive pain. There were no discernible differences between mothers' and fathers' responses.On the whole, health care workers thought EIMC was a safe procedure, and the outcome was aesthetically pleasing. Nearly all EIMC study doctors and nurses expressed preference for the AccuCirc device over the Mogen clamp. We detail these findings below.Discussions suggested that most parents who had adopted EIMC initially had some anxieties; these came up mostly during the consent process. During the consent process, parents learned in greater depth the possible adverse consequences of EIMC. A father told how he had silently posed rhetorical questions during the consent process.I kept asking myself, “Isn’t it going to cause some deformities on the thing [penis]?” and “What happens if it [penis] starts decaying?” “What have been the results with regards to this exercise since they are saying it is research?” You know, research normally is research. Parents' initial anxieties came up mostly during the consent process.Despite assurances that the rate of EIMC-related adverse events is very low and also that, if an adverse event occurs, it is usually minor and easily resolved, most parents remained agitated during the procedure.I was so uncomfortable during the time I was sitting here [in the clinic boardroom] as I had been told that my child could possibly get injured during the process. Most parents who had adopted EIMC and who were interviewed after the infant had completely healed thought that the procedure was very safe. A mother remarked:Ha-a, it’s safe, 100%; it’s 100% safe. My son healed well. I didn’t have a problem with it. In terms of bleeding, he didn’t bleed that much. It was just some minimal bleeding and that was it. Also, I simply applied Vaseline and he healed quickly. I can say it’s 100% safe. Another mother expressed similar sentiments:It’s safe, the baby did not bleed, he was not sutured, and I did not have to immerse the wound in salt [salty water]. However, a father’s response suggested some uncertainty:Ya-a, it’s safe, but you always wonder if everything is okay because you don’t know and there is no way to know, you understand what I am saying? … You say to yourself, “Let’s hope I don’t end up regretting.” You always have that fear … and you say, “What if something didn’t go well?”… Like I am saying right now, there is no way one can tell whether or not everything was done successfully. Despite assurances from study staff that the procedure had gone well, this participant still had fears that his son’s reproductive capability may have been damaged during EIMC, and he was anxious about his son’s later fertility or sexual functioning. He also felt that he would only be able to tell once his son had grown up and became sexually active. This shows the extent to which some parents view EIMC as a procedure that involves more than just foreskin removal.Overall, parents who had adopted EIMC expressed satisfaction with the outcome. A mother remarked:First of all, it’s smart. Secondly, it [penis] now has a better “shape”… I think that’s why they have the slogan “PINDA MUSMART” [local slogan that promotes VMMC as hygienic]. It’s just a good thing. On the whole, parents who had adopted EIMC said they would circumcise their next newborn son. Furthermore, they stated that they would recommend EIMC to other parents.Parents who had adopted EIMC would recommend EIMC to other parents.Fear of immediate harm emerged as one of the major reasons that parents did not adopt EIMC. A few parents expressed concerns that the procedure and its associated complications  could possibly lead to an infant’s death. A father maintained:Ya-a, something might be said to be safe, but at the same time, everything has loopholes.… Somehow it might not succeed, you understand? It’s just a simple operation you know. An operation on the appendix is supposed to be safe. A lot of people have undergone that kind of operation, and some have died. There are things that we presume to be safe but are not necessarily safe. Such a concern as this one was based on the assumption that the infant’s penis was not only tiny but also “too fragile” for the procedure. A father asked:How do you really know that the child’s foreskin starts here and ends there? What if they overdo it and end up cutting some veins … ? Although some men mentioned that they had decided on EIMC for their sons because they themselves had undergone VMMC, it appeared that if fathers had found VMMC very painful, they were less likely to agree with male circumcision for their sons.What you as an adult go through … you imagine the pain and your son undergoing such pain at that age … Another father noted:… It [pain] was something that I still remembered very well … I thought of the pain that I had gone through and I refused … During phone interviews, a few parents also mentioned fear of pain as one reason for ultimately deciding against EIMC .Discussions suggested that cultural beliefs were a significant barrier to EIMC. For example, participants suspected that Satanists were conducting the EIMC research. A mother professed her initial fears:I don’t want to lie; I suspected that you were Satanists and that you may take the foreskin … I really don’t know the process, but I was just scared because I don’t want to lie. Satanists are present but we don’t know the organizations they work for … Another female participant who had adopted EIMC described how someone had scared her after the procedure.I met a certain woman who asked me if I had seen where the foreskin had gone. When I told her that I had not seen it but I had only been told that it would be incinerated, she said it was a real shame that I had chosen to sacrifice my child to Satanism. She insisted that I was supposed to have requested the foreskin and disposed of it myself. Men who did not choose EIMC for their sons stated in a group discussion that they would circumcise their sons only on condition that they would be allowed to take the removed foreskin with them.“My doctor said I should not do it” Perceptions such as these were a result of poor knowledge of the EIMC procedure; in fact, local anesthetic was applied prior to the procedure.Misconceptions were also prevalent among ancillary staff, including lay community health workers. The lay community health workers participating in the study were mostly hand-picked elderly women, many of whom had some basic education. A nurse said about them:They [lay community health workers] think the infant has to be anesthetized first [general anesthesia], so they assume that if infants are anesthetized, they will “never wake up” [implying dying]. Some have heard of people who have died after being anesthetized. The same nurse went on to state that these community workers often passed on misinformation to the communities where they worked. Given their misconceptions about EIMC, perhaps it is not surprising that the 50 lay community health workers based at the study clinic  did not refer a single infant for EIMC during the comparative trial, despite initial assurances that they would actively support the study.Discussions with non-EIMC study nurses also suggested that some of their peers gave mothers ambivalent or contradictory advice regarding EIMC.You hear them saying, “Ya-a, it’s a good thing to have him [son] circumcised, but if it was my son, I would not have him circumcised.” This quotation suggests once again that some health care workers did not promote EIMC.During discussions, study clinicians reported their initial anxieties with EIMC. A study doctor described her initial feelings:Before I underwent training, I thought EIMC was such a difficult thing. I couldn’t imagine infants being circumcised; I had never seen such a thing.… And then during the lectures when I was taught the various techniques and their complications, it was a bit scary. Another doctor described the EIMC experience as “mind-opening.” He elaborated:I had a preconception that the neonatal stage was the child’s most delicate period and that EIMC could predispose them to infections, would result in delayed wound healing, or anything like that. I never thought circumcision could be that safe and easy. Despite acknowledging initial anxieties, study doctors stated that, with more exposure and practice, they became confident conducting EIMC and subsequently began to feel that the procedure was both uncomplicated and safe.Now I am very comfortable. I now feel that EIMC is a procedure that you can even do with your eyes closed. Another doctor maintained:I think it’s a procedure that can safely be done not only by doctors but by any adequately trained health care provider. Study nurse-midwives also stated that, after assisting doctors with EIMC procedures, they now felt that they could safely perform the procedure.From what I have observed, I am very confident that I can also perform the procedure. When asked if she thought that nurses other than those involved in the EIMC study could also perform the procedure, a study nurse-midwife responded:They can. They are doing episiotomy; episiotomy is cutting a part that is even unmarked, a section you think the unborn baby might come through. Discussions suggested that on the whole, study doctors preferred the AccuCirc device over the Mogen clamp due to the former's safety features. A study doctor said:AccuCirc is straightforward and it’s a device that can protect. … We have that thing that protects the glans, so you don’t have to worry about anything … Another study doctor explained why he preferred the AccuCirc device over the Mogen clamp:I have realized that when using AccuCirc, there is less manipulation of the penis. With Mogen clamp, you manipulate the foreskin so much that the pen mark disappears just before you cut off the foreskin and so you won’t have a good approximation of the amount of foreskin that you should remove. As a result, you can either remove too little or too much foreskin. Just as with parents who adopted EIMC, study clinicians stated that the EIMC outcome was aesthetically pleasing. A study nurse-midwife commented:It’s indeed a sweet outcome; you actually feel proud of it. A study doctor felt that, compared with adult male circumcision, EIMC produced a better cosmetic result.EIMC has amazing results even when compared to adult MC [male circumcision]. I most liked the fact that the outcome was not only satisfactory to us as providers but to the parents and guardians of the infants as well. Informed by their experience with EIMC in the context of a small research trial, health care workers felt that it was feasible to roll out wide-scale EIMC for HIV prevention in Zimbabwe. On the whole, these health care workers felt that AccuCirc was likely to have several advantages over the Mogen clamp when it came to wide-scale implementation, including, for example, through rural clinics.Even nurses stationed at rural areas will be able to safely perform the procedure through AccuCirc, especially because the device is simple to use and the shielding ring makes it impossible to partially amputate the penile glans. Non-study nurses expressed optimism that, if adequately trained, they could safely perform EIMC using the AccuCirc device.The other time one of the study guys had a meeting with us, he clearly demonstrated how that white plastic gadget [AccuCirc] works. If we are trained, we will be able to perform the procedure. Also, we already have knowledge of some of the aspects such as sterile procedures. We can do it. Despite overwhelmingly recommending that nurses and midwives be trained and delegated to perform EIMC, nurses (both EIMC and non-EIMC) felt that these clinicians should be covered by doctors in case of any major complications.During the EIMC comparative trial, some parents called study staff whose mobile numbers were on the contact card (including at night) to report issues that the staff thought trivial . EIMC study clinicians wondered how these understandable parental anxieties would be addressed in the context of roll-out. Specifically, they questioned how the public health sector would be able to provide such intensive phone support.Will the public clinics and hospitals be able to put in place the necessary supportive mechanisms such as taking night phone calls? .EIMC study clinicians stated that, unlike disposable diapers, cloth diapers (the option used by most people) are less absorbent and perhaps changed less frequently, so that the baby was sitting in damp (cloth) diapers for long periods, resulting in delayed wound healing.… Some delayed wound healing we experienced had to do with the fact that mothers were using nappies [cotton or cloth diapers], but once we gave them the Pampers [disposable diapers], the babies subsequently healed very well. The same doctor went on to question the feasibility of purchasing large volumes of disposable diapers during EIMC roll-out.Will you be able to purchase Pampers [disposable diapers] for all those babies whose parents cannot afford Pampers during the roll-out? We nested a qualitative study within a trial that assessed the feasibility, safety, acceptability, and cost of rolling out EIMC using devices in Zimbabwe. The qualitative study enabled us to explore parental and health care workers' perspectives on EIMC conducted using devices, especially as they relate to EIMC safety, acceptability, barriers, and feasibility.,,Despite acknowledging initial anxieties with EIMC, parents expressed satisfaction with both the procedure and the outcome. These findings corroborate the EIMC trial findings, in which nearly all mothers (99.5%) reported satisfaction with the outcome,Despite initial misgivings, both parents and the clinicians who performed the circumcisions expressed satisfaction with the procedure and its outcome.Like parents, study clinicians, despite acknowledging initial anxieties with EIMC, reported satisfaction with EIMC. All felt that it is a simple procedure that can be performed by non-doctors. These opinions are especially important because they were expressed by health care workers experienced with the procedure. Moreover, based on their experience, clinicians felt that it was feasible to offer wide-scale EIMC for HIV prevention. Their recommendations need to be considered when planning EIMC scale-up, especially their recommendations that nurse-midwife providers should be covered by doctors in case of any major complications and that the AccuCirc device should be used during roll-out. Furthermore, issues concerning dealing with parental anxieties and EIMC wound management need to be carefully considered in the context of scale-up. The study also found a poor understanding of EIMC among health care workers not involved in conducting the procedure, highlighting the importance of adequate training of these stakeholders.,–,,Parental reasons for non-adoption of EIMC included fear of harm, cultural beliefs, and misinformation from health care workers. These findings are similar to those of EIMC hypothetical acceptability studies.Additionally, communication materials need to highlight the several advantages of circumcising males during infancy rather than later in life. The materials also will need to include a “frequently asked questions” section that specifically addresses the parental concerns raised in this and other studies. Engaging satisfied parents to promote circumcision will be an important strategy to allay other parents’ fears. It may also be important to develop quality standards to assess provider–client communication, with a view to assuring the quality of the EIMC counseling process.Engaging satisfied parents to promote circumcision will be an important strategy to allay other parents’ fears.The finding that painful VMMC experiences among adult men leads them to reject EIMC for their sons has at least 3 implications for VMMC roll-out in general and EIMC promotion in particular. First, adult VMMC programs need to manage clients’ pain adequately. Second, VMMC clients circumcised via conventional surgery need to be empowered so that during the procedure they will alert providers whenever the anesthesia is not adequate. Last, EIMC awareness campaigns need to explain the differences between adult conventional surgery and EIMC—especially the fact that the latter does not require an anesthetic injection, sutures, or dipping the post-circumcision wound in salty water, often considered painful.,Correcting misconceptions around VMMC in general and EIMC specifically will be another important strategy in awareness campaigns to allay parental concerns. Awareness campaigns need to specifically address the persistent concern about the discarded foreskin.Awareness campaigns need to specifically address the persistent concern about the discarded foreskin.,This qualitative study was nested within the first randomized comparison of AccuCirc and Mogen clamp devices for EIMC in sub-Saharan Africa. The advantages of conducting qualitative research with or within trials are now well recognized. For one thing, the qualitative components of trials gather information that helps to answer research questions in depth.actual as opposed to hypothetical acceptability and feasibility of EIMC among parents, study clinicians, and non-study clinicians. Triangulation has been widely adopted in qualitative research as a means to investigate the validity of both the data and the conclusions derived from them.This study also triangulated various data collection methods  to explore the A potential limitation of this study is that budget and time constraints limited our sample to 12 in-depth interviews, 4 focus group discussions, and 95 short phone interviews with parents. It could be argued that parents with newborn sons who declined to participate in the trial (n = 984) were not adequately represented. It is also possible that we did not fully explore all themes due to the relatively small sample.This qualitative study enabled us to explore parental and health care workers’ perspectives on EIMC conducted using devices. Parents who opted for EIMC and EIMC providers felt that EIMC was a safe and acceptable procedure that would likely be more widely adopted over time. However, some parents and health care workers without experience or knowledge of EIMC feared that the procedure might be harmful or painful. These findings will be used to inform the design of a demand-generation intervention to support wider adoption of EIMC.Parents who opted for EIMC and EIMC providers felt that EIMC was a safe and acceptable procedure that would likely be more widely adopted over time.


Prevention researchers have found that drinking in different contexts is related to different alcohol problems. Where and with whom people drink affects the types of alcohol-related problems they experience. Consequently, identifying those contexts that result in the greatest number of problems provides a novel opportunity to target new prevention efforts aimed at those contexts. However, identifying these contexts poses methodological challenges to prevention research. To overcome these challenges, researchers need tools that allow them to gather detailed information about when and where people choose to drink and how contextual factors influence drinking risks. New data collection and analysis techniques, such as activity-space analysis, which examines movement through different contexts, and ecological momentary assessment, which captures microlevel contextual changes as individuals move through their days, can advance the field of alcohol studies by providing detailed information on the use of drinking contexts, particularly when combined. Data acquired through these methods allow researchers to better identify those contexts where and conditions under which drinking and problems related to drinking occur. Use of these methods will allow prevention practitioners to target prevention efforts to those contexts that place most drinkers at risk and tailor prevention efforts to each context for specific outcomes. The study of drinking contexts has become an increasingly fertile area of research in prevention science. Each drinking event has a series of contextual characteristics unique to that event. Where (location), when (the sequence of events), with whom , and under what circumstances (situation characteristics) a person drinks affect the types of alcohol-related consequences a person experiences. Taken together, these contextual characteristics may exacerbate or buffer an individual from experiencing alcohol-related problems. Through the identification of high-risk contexts, a selective prevention approach  can be aConsider the following scenarios: After the senior prom, a girl goes to her boyfriend’s house for the night with a group of friends and their dates. The parents, who are hosting the party, set up the party but stay in their room to keep out of the way and let the teens enjoy themselves. The teens all think that the parents do not care if anyone drinks. Some already have consumed alcohol at the prom, and others invite along additional friends they know, some of whom are 21 years old. In another scenario, after the prom, another girl goes to the official “after party” hosted by the school at a local bowling alley. Because this party is hosted by the school, several parent chaperones are present. Some of these teens also have consumed alcohol at the prom, but they do not expect that they will be able to do so at the school-sponsored after party. In each scenario, the drinking context either provides specific risks for young people or buffers them from those risks. In the first example, the young people are at risk for drunkenness and other related problems, such as risky sex, arguments, and fights. In the second example, alcohol-related consequences are minimized, because contexts for both drinking and problems are constrained.Recent research has found that different drinking contexts present unique risks for several social problems. Drinking at fraternity and sorority houses or events is related to more drinking-related problems among college students , includiThis article presents a social ecological model that explicates relationships among key individual and contextual factors involved in alcohol use and alcohol-related problems. This is followed by a discussion of two complementary approaches to obtain the detailed information necessary to examine these relationships: activity-space analysis (ASA) and ecological momentary assessment (EMA). ASA highlights the importance of examining movement through different contexts and its resulting impact on drinking behaviors and related problems. EMA is a methodological tool that captures microlevel contextual changes as individuals move through their days. Integration of these two approaches in studying risks for alcohol-related problems can (1) provide a framework for identifying the key contextual elements that place drinkers at risk, and (2) allow researchers to examine linkages in time among behaviors, contextual elements, and where people regularly spend time.Alcohol-related problems are affected by individual characteristics; the situational, social, and locational characteristics of drinking contexts; and alcohol use. Individual characteristics refer to demographic and psychological factors such as impulse control, self-efficacy, risk-taking propensity, and drinking expectancies. The selection of different drinking environments seems to be correlated with a variety of different personal characteristics such as gender, age, and ethnicity and personal characteristics such as impulsivity, risk taking, drinking expectancies, and beliefs . In the Situational characteristics refer to those features of a context that change from one drinking event to another, such as time of the day, level of parental supervision, or legal and social constraints. For example, it may be that specific locations place constraints on behavior such that some alcohol-related problems  may be less likely to occur at someone else’s home  or restaurants and bars  but more likely to happen at less supervised locations such as parks and beaches. People who drink often at bars may be concerned about potential legal ramifications of fighting in bars and may be more likely to become aggressive at home (toward an intimate partner or children), where fewer individuals are present to stop the abuse .Social characteristics refer to the collective attributes of people and their relationships in drinking contexts. These characteristics also are temporal and change from one drinking event to another. An intimate house party with friends and significant others has different risks than a large party at a bowling alley where a person may or may not know all the other attendees. Social characteristics of the drinking context, such as number of people, gender or age composition, peer expectations, and drinking behaviors of social-network members also may be important determinants of alcohol-related consequences. Male college students reported greater frequency of drunkenness in large groups of mixed-gender and small groups of same-gender individuals compared with small mixed-gender groups . ParentsReturning to the prom example, a high-school freshman female who attends a party at which alcohol is served may have little experience with alcohol and may feel awkward because the majority of prom-goers are juniors and seniors, but she decides to drink at the after party to fit in with the rest of the group. The number of people drinking at the after party  may place her at higher risk for alcohol-related consequences  than some of her peers who did not attend that party. Importantly, alcohol may not be a necessary ingredient for some problems, because this setting may draw together people with intentions to engage in risky behaviors, regardless of the amount they consume. Therefore, distinguishing the roles of alcohol in these social processes in drinking contexts is important.Location characteristics, such as proximity to sources of alcohol or the necessity of using a motor vehicle to get from one place to another, will further affect the likelihood that one will experience negative outcomes. Within these contexts, alcohol use affects the rates at which problems will occur. Drinking in places with higher densities of alcohol outlets may increase bar hopping . In addition, the availability of drinking places outside the home almost invariably leads to greater exposures to risks related to driving after drinking . These rIndividual, situational, social, and locational aspects of drinking environments are temporal and change over the course of a day or evening. To further understand the social mechanisms by which drinking contexts affect alcohol use and drinking-related problems, it is important to assess the relationships among these different aspects of drinking contexts, drinking behaviors, and drinking-related outcomes over time. Thus, researchers need to collect detailed data that identifies where people spend time on a regular basis, whether alcohol is consumed in those settings, and with whom respondents are spending time. For example, a high-school student may start his or her day at home, leave for school, go to a part-time job, head over to a friend’s house to study, and end the day back at home. While at his or her friend’s house, he or she may find the liquor cabinet open and available for use. A parent also might start his or her day at home, leave to take the children to school, drop off clothes at the dry cleaner before heading into work, walk to a lunch meeting near the office, stop at the grocery store for some dinner items on the way home, pick up the children from an after-school program, and take them to activities before heading back home for the night. While at lunch the parent may find time to have a drink with a friend. In each of these different places, an individual’s risk for alcohol use or related problems will be a function of effects related to physical access to alcohol , the social interactions that may occur within places , and individual proclivities to drink.As suggested here, location characteristics such as proximity to alcohol outlets are only one of several key components for understanding the roles of drinking contexts in drinking and related problems. Historically, these characteristics have been measured using standard geospatial approaches. Such approaches most often include the use of spatial data in Geographic Information Systems to map locations of alcohol outlets relative to locations where people live and presumably spend much of their time. Thus, almost all previous and current research on the physical availability of alcohol through outlets and alcohol-related problems has focused on local residential and commercial environments using administrative areas such as Census tracts or ZIP Codes . Such stUnderstanding the geographic distribution of “activity spaces” requires individual respondents to provide geographic information on where they regularly spend their time, at minimum, or a daily listing of where they go during each day, including the routes the individual has traveled to get to those places, at maximum. Activity spaces consist of the places that an individual has visited and the routes and areas the individual has traveled throughout each day. The way individuals use their environments, represented by their activity spaces, and social relationships within these spaces may mitigate or exacerbate drinking and related problems. Assessments of the structures of these spaces may provide better measures of exposures to alcohol use and related harms. The examination of activity spaces also can help explicate how exposure to an alcohol environment may differ between drinkers and nondrinkers, affecting their level of risk. Research has not determined (1) whether greater physical access to alcohol increases the risk for alcohol-related problems  for both drinkers and nondrinkers, and (2) the social mechanisms that may explain why differences may or may not exist.Researchers need reliable methods to collect specific geographic information that links the social mechanisms under study to the theoretical statements that tie behaviors to specific geographic locations. For example, an analysis of the mechanisms by which different types of social support , drinking behaviors of network members, and use of on-premise drinking places interact to increase risks for different forms of child neglect  would require identification of locations at which adults were present when these events take place  . HoweverThe few studies that have measured activity spaces have done so with primarily school-aged youth and small sample sizes and in isolated geographic areas , limiting generalizability . These sChallenges do exist when collecting these types of data. Activity-space data require that respondents provide locations that can be geocoded to report those points. Respondents may not always accurately report those locations. For example, when asked to pinpoint a location using names of two streets that intersect, they may name two parallel streets or identify two streets that do not intersect. This can be overcome by using GPS technology to track individuals’ movements across space. However, use of GPS often results in large amounts of data for each individual, making it difficult to analyze . FinallyRecent research on substance abuse has combined activity space approaches with GPS devices to document micro-movements across space with information elicited at regular intervals from the respondent via EMA . This acIn addition to specific geographic risks within an individual’s activity space, that space may include certain types of social contacts that may either buffer him or her from risks associated with the physical availability of alcohol or exacerbate those risks. A parent who spends time with impulsive social-support members at bars where violence occurs regularly may internalize those norms, placing his or her children at greater risk of being physically abused . These tActivity-space analysis represents a step beyond the standard use of geospatial data to identify exposures to drinking contexts, opportunities to drink in those contexts, and problems related to those contexts. However, by themselves, activity-space analyses do not provide information about specific characteristics of drinking events that may be relevant to the further elucidation of the social processes that lead from opportunities to drink to drinking risks. Situation and social characteristics see  may be bEMA refers to a range of methods that involve collection of real-time data that can be used to describe a person’s behaviors and experiences throughout the day in his or her natural environments . MomentaA few limitations and challenges of the EMA approach should be considered . First, Despite these potential limitations, there is great value to using EMA to study the role of drinking contexts in alcohol-related problems. First, EMA may obtain a more accurate report of behaviors and experiences in people’s natural environments. Traditional survey methods use predefined categories of drinking locations  and contextual characteristics that fail to provide an accurate picture of the wide range of drinking contexts that people encounter. Also, when asked about the past year, past month, or even past 24 hours, people may not accurately recall locations, setting characteristics, and drinking behaviors that were specific to a particular event. EMA attenuates recall errors and provides rich and descriptive event-specific information . The eveHuman behaviors change over time and across situations. Further, people’s experiences, choices, and behaviors in one situation are likely to affect their experiences, choices, and behaviors in another situation. For example, it is possible that supportive characteristics for aggression in the first drinking event  will contribute to the likelihood of engaging in physical aggression over the course of an evening. Therefore, such behavior may only manifest in the second or third drinking context with fewer legal ramifications. EMA data are necessary for understanding individuals’ experiences, choices, and behaviors over time and across contexts to establish knowledge about the potential dynamics by which contextual characteristics affects alcohol consumption and drinking-related problems.Previous studies have used EMA approaches to study alcohol craving, use, dependence, and other drinking problems among youths, young adults, and adults e.g., . These sA common EMA approach to studying drug use behaviors asks respondents to initiate assessments when they are involved in the alcohol or other drug (AOD) use behavior  . They also are prompted at random times to complete similar assessments when not using AODs. Alternatively, study participants are prompted to respond to assessments at regular intervals or random times . A recenIn the authors’ ongoing project, EMA data about drinking contexts, drinking behaviors, and related problems will be collected from 16-to 19-year-olds using cell phone interactive voice-response (IVR) surveys to assess the characteristics related to greater problems among youth. No GPS tracking data will be collected in conjunction with these EMA reports. Assessments will be collected at six time points  on 2 weekends over 2 consecutive weeks. Each time, participants will receive invitation calls on their cell phones to respond to a brief survey. In conjunction with survey data of youth individual characteristics , these EMA data will be used to address important questions related to where, when, and under what conditions youth experience specific problems.In sum, the episodic-and context-based nature of AOD use makes the EMA approach appropriate for studying such behaviors . EMA metEach drinking event has a set of characteristics unique to that event. Previous research has shown that these characteristics affect the types of alcohol-related consequences that individuals experience. However, to design focused environmental prevention programs   aimed atAn example of prevention programs that make use of the contextual information targeting adolescent drinking would be informational apps for parents in which they can identify risky contexts. For example, an app could ask parents to obtain and provide information such as the location of the party  their child wanted to attend, potential supervision, number of guests, and the likelihood of legal drinkers in attendance. The app would help parents identify the kinds of parties that are most dangerous to teens and offer guidance to reduce risks related to underage drinking, including guidance on local social host laws, actions to contact social hosts (unwitting or otherwise), and access to police and social service agencies. Part of the success of such an intervention might be the experience of going through a checklist that reminds parents to have conversations with their children about drinking risks and helps them explore their concerns with their children. Another app, similar to the LiveSafe app being implemented on college campuses, might encourage underage youth to report instances of drinking and related problems via text messages to the police. This information would allow police to intervene more quickly in contexts where risky drinking or alcohol-related problems have occurred. Perhaps more importantly, the app provides encouragement to youth to recognize and respond to risks in their drinking environments.The social ecological framework presented here is a starting point to identifying aspects of the drinking environment that expose individuals to increased risk for alcohol-related problems. Activity-space analysis and EMA are the most suitable approaches to study these aspects and examine the mechanisms by which risk may occur. Individually, both of these approaches can test various aspects of the social ecological framework presented. However, integration of both provides a richer understanding of the underlying contexts that result in problems. Additional challenges may exist when integrating these types of data. First, training of study participants on the protocol, the assessments, and any device used is an essential aspect of such studies. Second, ethical considerations must be addressed when tracking an individual’s location and associated behaviors, because the protocols are detailed, data intensive, and potentially may intrude on other protected behaviors . Third, the use of GPS technology and the EMA approach often result in large amounts of observation data for each individual, making it important to develop appropriate analysis strategies to answer key research questions . FinallyDespite these challenges, we believe that the integration of EMA and GPS data offers a great opportunity to overcome limitations of current research and enhance our understanding of the social mechanisms that underlie associations between drinking contexts and drinking-related problems. Revisiting the prom example, data from both activity-space analysis and EMA can help in theorizing how individual characteristics , contextual characteristics , locational characteristics , pre-and postevents, and alcohol consumption (drinking before the event) interact to result in problem behaviors. Further understanding of such mechanisms has the potential to advance prevention theory, current research, and context-based interventions to prevent alcohol-related problems.


Malnutrition is common in hospitalized medical patients and is associated with poor clinical outcomes. Whether malnutrition has a direct link to adverse outcomes or is rather a mirror of the severe patient condition remains debated. Our aim was to study the association of acute and chronic malnutrition status with blood biomarkers from different pathophysiological concepts to better understand the underlying mechanisms of malnutrition.We prospectively followed consecutive adult medical inpatients hospitalized between February 2013 and October 2013 in a tertiary care Swiss hospital. Nutritional risk was assessed using the Nutritional Risk Screening (NRS 2002) score, which incorporates acute and chronic measures of malnutrition. Multiadjusted regression models were used to investigate the associations between acute and chronic nutritional risk and biomarkers mirroring inflammation , stress (copeptin), renal dysfunction , nutritional status , and hematological function . Biomarker levels were transformed into deciles due to skewed distributions.P = 0.0021, PCT 0.28, P = 0.003, proADM 0.4, P < 0.001, copeptin 0.44, P < 0.001, urea 0.28, P = 0.002, vitamin D25 -0.23, P = 0.012, albumin -0.6, P < 0.001, hemoglobin -0.5, P < 0.001, RDW 0.46, P < 0.001. These associations remained robust after adjustment for sociodemographics (model 1), comorbidities (model 2) and main medical diagnosis (model 3). Subgroup analysis suggested that mainly the acute part of malnutrition and not chronic malnutrition was associated with an increase in biomarker levels.A total of 529 patients  were included. Overall, there was a significant association of NRS and most biomarkers of inflammation, stress, renal function, nutrition and the hematological system (coefficient and 95% CI): CRP 0.021, Acute malnutrition was associated with a pronounced inflammatory response and an increase in biomarkers from different pathophysiological systems which may partly explain the link between malnutrition and adverse medical outcomes. However, interventional trials are needed to prove causal relationships.


Key elements of Lesotho’s phased introduction of early infant male circumcision were strong commitment from the Ministry of Health and donors; adequate training and supervision; integration with maternal, newborn, and child health; and appropriate communication. Challenges around cultural acceptance, the availability of health care providers, and task sharing will need to be addressed. Key elements of Lesotho’s phased introduction of early infant male circumcision were strong commitment from the Ministry of Health and donors; adequate training and supervision; integration with maternal, newborn, and child health; and appropriate communication. Challenges around cultural acceptance, the availability of health care providers, and task sharing will need to be addressed. The World Health Organization and the Joint United Nations Programme on HIV/AIDS recommend early infant male circumcision (EIMC) as a component of male circumcision programs in countries with high HIV prevalence and low circumcision rates. Lesotho began incorporating EIMC into routine maternal, newborn, and child health (MNCH) services in 2013 with funding from the United States Agency for International Development and United Nations Children’s Fund. This presented unique challenges: Lesotho had no previous experience with EIMC and cultural traditions link removal of the foreskin to rites of passage. This process evaluation provides an overview of EIMC implementation.The Lesotho Ministry of Health and Jhpiego conducted a baseline assessment before service implementation. Baseline information from an initial assessment was used to develop and implement an EIMC program that had a pilot and a scale-up phase. Key program activities such as staff training, quality assurance, and demand creation were included at the program design phase. Facilitating factors and challenges were identified from a review of information collected during the baseline assessment as well as the pilot.Between September 2013 and March 2015, 592 infants were circumcised at 9 sites: 165 (28%) between 1 day and 6 days after birth; 196 (33%) between 7 and 30 days, and 231 (39%) between 31 and 60 days. Facilitating factors included strong support from the Ministry of Health, collaboration with stakeholders, and donor funding. Providers were enthusiastic about the opportunity to offer new services and receive training. Challenges included gaining consent from family members other than mothers, and parents’ concern about pain and complications. The EIMC program also had to manage providers’ expectations of compensation because overtime was paid to providers who took part in adult circumcision programming but not for EIMC. Limited human resources, including authorization only for doctors to perform EIMC, impeded provision of services.Despite communication, compensation, and task-shifting challenges, integrating EIMC services with MNCH services could be a sustainable model for EIMC service delivery in Lesotho. President’s Emergency Plan for AIDS Relief (PEPFAR), and the United Nations Children’s Fund (UNICEF).2007: Male circumcision task force formedFebruary 2012: Ministry of Health (MOH) launches voluntary medical male circumcision (VMMC) servicesFebruary 2013: MOH commits to introduction of EIMC servicesApril and May 2013: Rapid assessment of initial facilitiesSeptember 2013: 4-month pilot launchedFebruary 2014: Start of phased scale-up,,As per WHO guidance, VMMC programs need adult circumcision to reach 80% coverage and EIMC to be institutionalized to maintain the benefit of the fast scale-up of the adult circumcision program.,According to WHO guidelines, EIMC is safe for full-term infants who weigh more than 2.5 kg and who have the procedure from 12 to 24 hours through 60 days after birth under local anesthesia and with the use of WHO-recommended devices.,,EIMC projects have faced challenges around uptake of services in East and Southern Africa, where, unlike in West Africa, infant male circumcision is not commonly practiced.On the service side, in most countries in East and Southern Africa, only physicians are licensed to provide male circumcision, while nurse-midwives and nonphysician clinicians are the primary care providers during and after delivery.,Lesotho has one of the highest HIV prevalence rates in the world, with an estimated 23.7% of adults infected.Modeling studies have estimated that for every 5 circumcisions in Lesotho, 1 HIV infection would be prevented.In 2013, the MOH established an EIMC task force within the Family Health Division, which oversees MNCH activities. The MOH held meetings to present the strategy and to determine the best approach to introduce EIMC in Lesotho. Meetings brought together a number of experts from United Nations (UN) agencies and other organizations supporting the MOH in the implementation of core HIV prevention and treatment programs. Stakeholders included MNCH, sexual and reproductive health, and family planning technical leads in the MOH and members of district management teams, UN agencies, the Christian Health Association of Lesotho, international and local NGOs, and managers at the selected hospitals. These meetings were organized to discuss guidelines for EIMC services in Lesotho and to determine how provision of EIMC services could be used as an opportunity to strengthen other MNCH services.The proposed program model sought to integrate EIMC services into existing MNCH services, with EIMC provided to infant boys between 1 and 60 days after birth. The stakeholders developed a road map for implementation of EIMC services that included the comprehensive package of services recommended by UNAIDS .12The proposed program model sought to integrate EIMC services into existing MNCH services, with EIMC provided to infant boys between 1 and 60 days after birth.Information about EIMC for parentsProcesses to document HIV status of the mother; if not known, HIV testing and counselingAdherence counseling for mothers in the prevention of mother-to-child transmission of HIV program to continue with their medicationCounseling and consent from mother or parentsInfant feeding educationMessaging to reinforce postnatal visit on day 7Information to reinforce immunizationAftercare instructions—post-EIMC careAnalgesicsGeneral HIV prevention pamphletsCondom provision to mothersBased on programs in other countries, and after discussion and consultation with the EIMC task force, the Lesotho MOH chose the Mogen clamp for program scale-up, because it is a 1-piece device, it does not need to be assembled, and it can be reused after sterilization. Other devices under consideration are placed on the infants and require a return visit to the facility for removal, which is a challenge due to Lesotho’s mountainous terrain.Both doctors and nurses were trained on the EIMC procedure with specific roles. The procedure is performed only at the hospital level and only by doctors; however, trained nurses assist with the surgical procedure and perform follow-up care of circumcised infants. In Lesotho, either parent of the male infant can provide written consent for the procedure even though culturally fathers are expected to be the ones who authorize mothers to circumcise the infant.Supplementary Material 1: Facility readiness assessment form); a pilot phase at 2 facilities; and a moderate program scale-up phase with services being rolled out at 6 other hospitals and 1 health center. Members of the EIMC task force assessed each phase and drew up recommendations to inform the following phase.A pilot of EIMC services in Lesotho was conducted over 2 years from September 2013 to March 2015. A phased approach was used to ensure that all steps of program implementation were in place. Three phases were designed: a rapid assessment to gather baseline information regarding readiness of facilities as well as potential demand  after their selection by hospital management. The program procured equipment and supplied it at each site . Nurses conducted education on EIMC at antenatal care (ANC) clinics at hospitals and health centers. Circumcised babies were routinely assessed at 48 hours and 7 days after the procedure, either in the hospital or at their health center, to evaluate wound healing and to detect and document adverse events.Ethical oversight was provided by the Lesotho MOH. Data presented in this manuscript are anonymous and analysis was done without identifiers. Informed consent to circumcise the child was obtained from the parent after information highlighting benefits and risks of the procedure was given. The local institutional review board (IRB) and the Johns Hopkins University IRB provided approval for secondary data analysis.During the pilot, 45 providers, including 4 doctors, 25 hospital nurses, and 16 health center nurses were trained during 3 workshops to perform various aspects of EIMC services. During the scale-up phase, 149 health workers, comprising 131 nurses, 16 doctors, and 2 lay counselors, received training in 9 workshops at the 7 sites where services were scaled up .Between the start of the pilot in September 2013 and March 2015, 592 male infants were circumcised , includiOnly 1 mild adverse event was recorded during the reporting period, representing 0.2% of total circumcisions. No severe adverse events were recorded. The adverse event occurred on a procedure performed during a training activity by a trainee doctor on a 6-week-old infant at Mafeteng District Hospital. Upon completion of the procedure, it was noted that excessive skin had been removed from the shaft on the ventral aspect of the penis. The trainer on-site consulted with the master trainer off-site and a decision was made to allow for healing to proceed and to determine any remedial action at the infant’s follow-up visit after 48 hours. At the 48-hour visit, the wound was exposed and assessed. The infant was examined again at the seventh day post-circumcision and again at 4 weeks post-circumcision. By the third checkup and review visit, the wound was satisfactorily healed and the defect had been covered by new skin.From October 2014 through March 2015, 11%  of male babies delivered at the 9 implementation sites  were circumcised; rates ranged from 27% (81/299) in Berea Hospital to 2% (8/403) in Leribe Hospital.The rapid assessment in May 2013 provided information for upgrading sites to offer EIMC services. Specifically, it assessed MNCH programs in selected facilities, identifying opportunities and mechanisms for integrating EIMC services with MNCH services, sensitizing site managers and health care providers on the introduction of EIMC services in their facilities, and assessing the willingness of parents expecting a baby, should they have a son, to allow him to be circumcised.Supplementary Material 2: Interview questionnaire for potential parents).The methodology for data collection included interviews with site managers, health care providers, and expectant parents (and accompanying relatives) attending ANC services, data collection of key information , and direct observation of newborn care services .The rapid assessment was conducted at 2 sites that were considered for the pilot phase. These sites were selected as they were already offering VMMC (the doctors at those sites were trained for adult VMMC provision), and they were close to the MOH headquarters in the capital—for ease of monitoring. The 2 sites were Mafeteng District Hospital and Scott Hospital  at the hospital also showed an interest in EIMC services. The parents raised concerns about pain for the neonate, timing of the surgery, and potential negative consequences, such as mutilation of the newborn by the EIMC procedure. However, a majority of those interviewed thought that EIMC was good for health and reduced chances of infections.Establish an early infant male circumcision (EIMC) task team to oversee introduction of EIMC services in hospitalsDevelop guidelines and tools for service provision and monitoringContinue discussions around task sharing to allow nurses to perform EIMC procedures at both hospitals and clinicsImplement EIMC services where feasible on a daily basis, not on a weekly basis Develop EIMC information, education, and communication materials for communitiesSupplementary Material 4), a group education and counseling flipchart, a step-wise procedure chart to guide health workers in performing circumcision with the Mogen clamp, a complications pamphlet, and IEC brochures . Monitoring and evaluation tools, including registers, adverse event forms, and quality standards assessment tools, were also developed and piloted at the 2 hospitals. When finalizing EIMC guidelines, it became clear that there was a need also to finalize and update guidelines on essential newborn care.EIMC services were introduced at the 2 pilot facilities in September 2013. The objectives of the pilot were to introduce EIMC services at the 2 hospitals and to consider integration of EIMC services into MNCH services. Specific objectives included developing appropriate trainings for the Lesotho context; finalizing and implementing EIMC program guidelines; and ensuring targeted communication on EIMC services through the development and distribution of information, education, and communication (IEC) materials; as well as education of pregnant women. Key documents developed during this phase included guideline documents, “Minimum Standards for Performing Early Infant Male Circumcision”  availabilityTrain additional providers from existing and new service sites to ensure the expansion of servicesEnsure the quality of services at all sites by providing training for all managers and health care workers involved in service provisionEnsure that the few trained staff are scheduled to provide services daily to avoid missed opportunities due to staff unavailabilityA roll-out plan detailing steps to be taken to expand services nationally was developed with consideration of recommendations from the pilot . EIMC seEngage facility management teamConduct rapid site assessment—look at infrastructure and personnelConduct initial demand creation in hospital and communitySet up siteSelect and train providersInitiate servicesProvide supportive supervision and mentoringTraining for both the pilot and scale-up phases took place immediately before service initiation at each of the implementing sites. Eligible trainees were qualified and licensed health care workers, preferably working in the maternity unit or in the maternal and child health clinic at the hospitals where service initiation was being planned. Each training ran for 5 days, and doctors and nurses trained together. Trainers conducted regular visits and worked with EIMC trainees until they reached competency in the circumcision procedure and could identify and manage complications. Other components of the training included education and counseling for parents of male infants. Specific training was developed for nurses at health centers on providing education and counseling of prospective parents, pre-procedure screening to ensure infants were fit for circumcision, and post-procedure checkup and care.Each training ran for 5 days, and doctors and nurses trained together.Teaching methods included 1 day in the classroom for theory presentations and discussion, 1 day of practice with models at different skills stations, and 3 days of hands-on clinical practice with babies in the clinic. To ensure competence, trainers closely monitored and supervised the physicians and nurses during the first 5 procedures. Trainers assessed knowledge at the end of the training through an examination, and they assessed skills by observing each step of the procedure.The EIMC technical working group developed a communication plan to address myths and misconceptions about EIMC. IEC materials regarding EIMC services are continuing to be provided to the primary audience  at ANC clinics, maternity wards, postnatal clinics, clinics seeing children under the age of 5, and VMMC clinics. These IEC materials were also provided through routine community mobilization activities.Early in program implementation, the technical working group developed tools for quality assurance. The MOH, WHO, and Jhpiego conducted external quality assurance visits to all sites. Lesotho uses guidelines based on WHO’s quality assurance guidelines for male circumcision.In addition, each site has a quality assurance assessment team  that undertakes a quality assurance review, to identify performance gaps and to develop action plans to bridge those gaps. EIMC service providers and managers also conduct periodic self-assessments of their services to improve quality. The process helps providers develop a sense of ownership of the assessment findings so that they become involved in making recommendations and implementing solutions.While the EIMC program in Lesotho is still in the early stages, demand for services has increased slowly as the program has expanded from 2 to 9 sites.Supplementary Material 6: EIMC pilot implementation program assessment).Introduction of the EIMC program was supported by a strong commitment from the MOH, close cooperation with stakeholders , and stable funding from USAID and UNICEF. In addition, when providers were offered the chance to train, they were enthusiastic about the opportunity to acquire a new skill and offer new services. The phased introduction of services helped to ensure a smooth start-up and, where possible, recommendations from the assessment were applied to the pilot, and recommendations from the pilot were applied to the scale-up at 7 facilities .Providers being trained in EIMC now receive refresher training on neonatal care, which is important because of Lesotho’s high infant mortality rate.,The primary challenge to EIMC uptake in Lesotho is that even though either parent can provide consent individually, the mother still consults with the father and other family members before consenting to the procedure, as has been reported in other programs in Southern Africa.The primary challenge to EIMC uptake in Lesotho is the mother’s need to consult with the father and other family members before consenting to the procedure.In Lesotho, low rates of institutional childbirth (58.7%)Cultural practices also have an impact on uptake of EIMC services. Traditionally, boys in Lesotho are circumcised during ritual initiation into adolescence and adulthood.,Another challenge in Lesotho and supported by other studies is parents’ reluctance to have their baby boys circumcised due to concerns about pain, the infant being too young to undergo a surgical procedure, and potential harm.The program also had some difficulties integrating EIMC services into the MNCH program. The VMMC program in Lesotho is a stand-alone program that operates year-round from clinics and through seasonal campaigns. While MNCH providers have been enthusiastic about getting trained in EIMC service provision, this enthusiasm has been hard to sustain, one reason being compensation. Unlike VMMC providers, EIMC providers do not receive incentives for providing male circumcision services. The MOH sees the provision of EIMC services as part of the standard package of MNCH services and has not provided for extra compensation. As a result of the discrepancy, some MNCH providers have lost enthusiasm for including additional tasks in their already busy schedules. In addition, some hospitals that provided EIMC services for a fee before the launch of the official EIMC program are now expected to provide these services for free, which has undermined management buy-in.,A notable challenge is the lack of available providers, which is partly the result of a shortage of doctors, the only cadre authorized by their regulatory body to perform EIMC. However, under the new, recently revised preservice education curriculum, nurses are being trained to perform the EIMC procedure. In practice, most nurse clinicians are not sure they have the authority from their regulatory body and are hesitant to perform the procedure. Furthermore, nurse clinicians are a recently revived cadre and very few in number, and therefore they cannot meet the demand for EIMC services. There are fewer than 50 nurse clinicians for the entire country. All cadres of nurses should be authorized to perform EIMC to meet the growing demand. The need for task sharing of the male circumcision surgical procedures between medical doctors and nurses was identified before program inception and is seen in other programs as well.The introduction of EIMC services for HIV prevention into MNCH services in Lesotho demonstrates the feasibility of such a program in a low-resource setting with leadership and commitment from the MOH and key stakeholders. EIMC can be institutionalized to complement gains from the adult VMMC program.Allowing nurses to perform EIMC procedures would increase the availability of services in hospitals and would also allow the procedures to be performed in health centers, where a large number of potentially eligible infants are seen. Stakeholders should encourage the MOH and professional regulatory organizations to license nurses to provide EIMC services.Circumcision services should also be offered on a daily basis at implementation sites. Currently, EIMC services are offered once or twice a week at each site, based on the providers’ workload or on set service days. We also believe that the MOH should explore offering EIMC services on a daily basis at district hospitals. EIMC services would then be available during the 3 visits  that are most likely to present an opportunity for babies to be circumcised, and the mothers would not have to make a return visit, which is difficult for them.With only 1 adverse event reported during the assessment, we believe that this review will assist program implementers in Lesotho to tailor the national scale-up of services to their local context.