Polyethylene glycol is commonly used to manage constipation and is available with or without electrolytes. The addition of electrolytes dates back to its initial development as lavage solutions in preparation for gastrointestinal interventions. The clinical utility of the addition of electrolytes to polyethylene glycol for the management of constipation is not established.The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of functional constipation in adults.A systematic review was conducted to identify randomised controlled clinical trials that assessed the use of polyethylene glycol in functional constipation. The primary outcome was the mean number of bowel movements per week.Nineteen studies were included in the NMA . PEG and PEG + E are both effective, increasing the number of bowel movements per week by 1.8  and 1.9  respectively versus placebo and by 1.8  and 1.9  respectively versus lactulose. There was no efficacy difference between PEG + E and PEG  and there were no differences in safety or tolerability.Polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. The addition of electrolytes to polyethylene glycol does not appear to offer any clinical benefits over polyethylene glycol alone in the management of constipation. Constipation is a common gastrointestinal symptom with a reported mean prevalence of 15 to 17 % amongst the general population. The prevalence is as high as 81 % amongst older hospitalised patients and 95 % amongst patients taking opioid analgesics . ConstipPolyethylene glycol, a minimally absorbed osmotic laxative, is commonly used to manage constipation in both adults and children. It is a mixture of different sized compounds with an approximate mean molecular weight of either 3350 or 4000 g/mol and is available in formulations with the addition of electrolytes (PEG + E) or without electrolytes (PEG). Polyethylene glycol exerts its laxative action by increasing the water content of stools due to its ability to interact with water molecules  or standard error [SE]). When data was available for both bowel movements and complete spontaneous bowel movements per week the later data was used in the analysis. Where data was only available graphically, estimates of the values were extracted by scaled measurement. Where means were not available, medians and interquartile ranges were collected. All data were adjusted to mean number of bowel movements per week (plus standard deviation) to allow meaningful comparison between the studies. To assess secondary endpoints, data regarding safety, tolerability, and compliance or willingness to continue therapy were collected.All included studies were assessed for the risk of bias by two reviewers according to recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions . Each poStudies included in the analysis were grouped according to whether the polyethylene glycol investigated included electrolytes (PEG + E) or not (PEG) and then according to the comparator (placebo or different active controls).For all pairings where there was more than one study a direct estimate of the difference in mean number of bowel movements per week has been obtained using both a Bayesian fixed effects and a Bayesian random effects model  using SAS v9.3. In addition, all the available data have been combined using a network meta-analysis with a Bayesian random effects model fitted to assess the relative effectiveness of PEG and PEG + E . NMA wasThe mean stool frequency was treated as a continuous outcome and hence a generalized linear model with identity link and a normal likelihood distribution was fitted using SAS v9.3 PROC MCMC. Vague (flat) priors were used for all calculations. A normal distribution  was used for treatment effects and a uniform  for inter-study standard deviation. Each analysis was run with 200,000 simulations, 1000 burn-in and thin = 20. The sensitivity of the results to study quality was explored by re-fitting the NMA having excluded all studies with a high risk of bias.An overview of the study selection process is summarised in Fig. N = 7), lactulose (N = 1) or serotonin agonist (N = 1); nine studies compared PEG + E versus placebo (N = 5), lactulose (N = 1), serotonin agonist (N = 1) or bulk forming laxative (N = 1), plus one study involved both an active (lactulose) and placebo control group; and two studies made direct comparisons between PEG and PEG + E. Table Of the 20 qualifying studies; nine studies compared PEG versus placebo  patients had chronic constipation, [In the majority of the studies  agonists were not statistically significant. The direct comparison of PEG + E and PEG suggests that the difference in the mean number of bowel movements per week is negligible and not statistically significant . The relative effectiveness of both PEG and PEG + E versus placebo was maintained with sensitivity analysis including only studies with a low risk of bias.Table Twelve studies included in the systematic review provided data on the safety of polyethylene glycol , 29–31 ap = 0.07) [Only two studies provided data on patient compliance or willingness to continue polyethylene glycol therapy. In a placebo-controlled study, compliance was lower with PEG + E as assessed by the mean number of sachets used per week . In a di = 0.07) .The aim of this network meta-analysis was to assess the relative effectiveness of polyethylene glycol with and without electrolytes in the management of functional constipation. The addition of electrolytes to polyethylene glycol did not enhance clinical effectiveness compared to polyethylene glycol alone.This NMA and the direct head-to-head random effects meta-analysis are consistent and confirmed that both PEG and PEG + E are effective treatments for constipation. Comparisons with placebo were highly significant, with PEG and PEG + E increasing the number of bowel movements per week by 1.8 and 1.9 respectively. These results are consistent with previously published meta-analysis where polyethylene glycol (PEG and PEG + E grouped together) was found to increase the mean number of bowel movements per week by 1.98 versus placebo . Our resNo safety signals emerged that would suggest that the addition of electrolytes provided any safety benefits to the use of polyethylene glycol in the management of constipation. Although most of the studies in this systematic review were of short duration, this finding is consistent with a long-term open label study of PEG. Over the 12 month study period no clinically significant changes in haematology or blood chemistry, particularly electrolytes, were observed amongst the whole study population or in older participants .Overall the tolerability of PEG and PEG + E was found to be good and often comparable to placebo. The majority of adverse events were gastrointestinal and were rated as mild to moderate in severity. Withdrawals due to adverse events were uncommon with both PEG + E and PEG. From a safety and tolerability perspective the addition of electrolytes to polyethylene glycol does not appear to provide any additional clinical benefits in the management of constipation.p < 0.0001) with 84 subjects preferring the taste of PEG whilst only seven subjects preferred PEG + E [PEG is a tasteless and odourless and can be mixed with the beverage of the patient’s choice . Althoug PEG + E . Palatab PEG + E , 35. In  PEG + E  which maAs with any systematic review, the quality of the studies and the heterogeneity of the study populations included in the analysis present a limitation of this study. There were only four studies considered to have a low risk of bias. Five studies were crossover studies, only two which had washout periods, , 27 hencDespite the high prevalence of constipation in the elderly and the frequent use of laxatives in this patient population, there is a paucity of clinical trials evaluating the safety and efficacy of polyethylene glycol in the elderly. This represents an important evidence gap.This network meta-analysis has confirmed that polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. There was no difference in the number of bowel movements per week and there appears to be no differences with respect to safety or tolerability between the two preparations. The addition of electrolytes in this clinical setting does not appear to offer any clinical benefits over polyethylene glycol alone.


Promoting active travel is an important part of increasing population physical activity, which has both physical and mental health benefits. A key benefit described by the then Scottish Government of the five-mile M74 motorway extension, which opened during June 2011 in the south of Glasgow, was that the forecast reduction in motor traffic on local streets would make these streets safer for walking and cycling, thus increasing active travel by the local population. The aim of the study was to evaluate the impact of new motorway infrastructure on the proportion of journey stages made actively (cycling or on foot) by individuals travelling in and out of the local area.n = 435 (2009–10), 543 (2012–13)), (2) a comparator area surrounding an existing motorway (n = 477 (2009–10), 560 (2012–13)), and (3) a control area containing no comparable motorway infrastructure (n = 541 (2009–10), 593 (2012–13)). Multivariable, multi-level regression analysis was performed to determine any between-area differences in change in active travel over time, which might indicate an intervention effect. Reference populations were defined using two alternative definitions, (1) Glasgow City and (2) Glasgow and surrounding local authorities.Data for the periods 2009–10 and 2012–13 were extracted from the Scottish Household Survey (SHS) travel diaries, which record each journey stage made during the previous day by a representative sample of the Scottish population aged 16 and over. Each individual journey stage was assigned to one of the following study areas surrounding existing and new transport infrastructure: (1) an area surrounding the new M74 motorway extension  contains supplementary material, which is available to authorized users. Increasing the proportion of journeys which are walked or cycled (‘active travel’) is an important component to increasing population level physical activity, which can translate into physical and mental health benefits of significant magnitude , 2. A rePhysical Activity and The Environment’ guidance published by the UK National Institute for Health and Clinical Excellence (NICE) in 2008 All stages: All stages regardless of distance travelled. [b]All stages greater than 0.5 km (kilometre): Stages so short a distance that it is reasonable that they could only be walked or cycled were excluded. [c]Stages less than 5 km only: Stages that were of such a long distance that they are likely only to be walked or cycled by enthusiasts were excluded. And [d]Stages greater than 0.5 km and less than 5 km: Excluded stages due to both definitions described in [b] and [c] above.The purpose of the second sensitivity analysis is to assess the extents to which including or excluding journey stages that were either certain or unlikely to be 'active' impacted on our results. For example, a journey over 6 km in distance is likely to be made using a motorised transport mode. We examined the effect of assessing journey stages for which there may reasonably have been a ‘choice’ of mode. This used the following four definitions: During the period 2009–10, 3706 participants in Glasgow and its surrounding authorities completed a SHS travel diary; 43.9 % (n(number):1627) males , and a substantial proportion were retired (2009–10: 25.9 % and 2012–13: 26.2 %); reflecting the older demographic of the sample. Most of the population described their health as fair to very good (2009–10: 93.3 % and 2012–13: 91.5 %).The numbers of journey stages completed by individuals during 2009–10 and 2012–13 are presented in Table The total number of stages included in 2009–10 by study area were South (n:435), East (n:477), and North (n:541). There were more stages included for 2012–13: South (n:543), East (n: 560), and North (n:593).The probability of a stage being made ‘actively’ increased in all study areas Fig. . Althougp = 0.003).The likelihood of an active stage was modelled for the periods 2009–10 and 2012–13 for each study area against the reference category Glasgow and surrounding authorities  influenced the likelihood of an active stage, the sensitivity analysis provided no changes in the results  and North (Control) had an increased odd ratio of an active stage during 2012–13 when compared to Glasgow and its surrounding authorities in 2009/10 Table .Table 4IThe aim of our study was to describe (a) recent changes in active travel over time and, (b) whether the opening of the M74 extension in Glasgow produced any between area differences in change compared to journeys completed in a comparator, control and wider city area. We found increases in the proportion of journey stages made using active travel from 2009–10 to 2012–13 for all study areas and both Glasgow and surrounding local authorities, and Glasgow City. There was no significant change in the likelihood of a journey stage being ‘active’ for people living near the M74 extension compared to Glasgow and surrounding authorities, and in a comparator area. There were small increases in the proportion of stages using active travel and the probability of a stage being made actively.Therefore in evaluating whether the opening of the M74 extension had an effect on active travel in the local area: we found no clear evidence that the M74 extension alone had either increased or decreased actively travelled journey stages in the local area. Increases in active travel were more likely due to changes in active transport for the region as a whole.The potential effects of the M74 extension on local residents were considered prior to its construction  and descCross-sectional surveys conducted in three areas of the UK  prior to new walking and cycling infrastructure described that for obligatory journeys people tended to choose the fastest mode of transport available to them . This isA stimulating built environment around the home containing interesting things to look at increases the likelihood of physical activity . It is dThe results presented in our study showed increases in stages being made actively from the period 2009–10 to 2012–13 in Glasgow and surrounding authorities, and all three of our study areas. In England between the periods 2012–13 to 2013–14 there were no countrywide increases in cycling and walking, however there were regional differences in uptake and 35 local authorities reported significant increases in the proportion of local people who cycled one or more times a week .In encouraging people to build physical activity into their daily lives it has been suggested that tackling environmental, structural and financial barriers to active travel should be prioritised . In the New urban motorway infrastructure in the UK is rare; therefore both the anticipated and true impact of the M74 extension on active travel is unknown; arguments made during the consultation phase lacked a clear evidence base. Construction provided a unique opportunity to conduct a natural experiment to understand the impact of the M74 extension on active travel behaviours of local residents. This evidence will have significant importance for future urban transport developments both in the UK and other nations world-wide.There are important strengths and weaknesses in the study design which should be considered when drawing final conclusions. The SHS travel diaries are part of an on-going repeat cross sectional survey which includes a large randomly selected and representative population. To describe between area differences in active journey stages between areas of Glasgow and surrounding authorities, individuals were assigned to one of three study areas based upon whether their residential intermediate zone was fully or partially located within a study area. This method is not as accurate as assigning a person to an area using a full postcode as sometimes these intermediate zones cover large geographic areas. Due to data protection concerns, the data we obtained did not include precise postcode locations to allow matching . The maiThe SHS travel diary dataset collects information for all stages of a journey undertaken between the ultimate start and end destination of a journey. This allowed us to analyse stage data and increase the final numbers included in our analysis. The SHS calculated journey distances using straight line linear distance between two postcode points. This may under report the true distance of a journey where routes cannot follow this path and are usually longer.reasonable transport mode choice’ defined as over 0.5 km and under 5 km when measuring the likelihood of active travel [The likelihood of a stage being made either by foot or cycled may largely depend upon the distance travelled and longer stage distances are negatively associated with active travel . A recene travel . This asAlthough there are limitations when using national datasets such as the SHS travel diaries, our study in part shows the potential and benefit of using routinely collected data. The dataset we analysed included almost 8000 people completing 21461 journey stages over two time periods across Glasgow and surrounding authorities. Using these data for research purposes incurred no charges and compared to collecting our own study data for this number of people it would have been both burdensome and expensive.Glasgow, the largest city in Scotland, displayed small increases in the proportion of journey stages which were walked or cycled but there were no between area differences in change in active travel for people living near the new M74 extension when compared to Glasgow and surrounding authorities. It must be noted that although there was not a significant increase in active travel journeys made by local residents, neither was there a decrease.Although we found little city-wide variation in active travel, recent studies have suggested that there is regional variation in increases in active travel. Future studies exploring regional variation and inequalities in active travel could provide more understanding of whether changes in active travel in Glasgow are comparable to other UK cities and large urban areas.The M74 extension is here to stay, therefore it is now important that transport activity and active travel monitoring continues in the area. The Scottish Government maintains this at a national level through the National Indication: Public or Active transport, which aims to ‘Increase the proportion of journeys to work made by public or active transport’  as captuCI, confidence interval; KM, kilometre; LL, lower level; N, Number; NHS, National Health Service; NICE, National Institute for Health and Clinical Excellence; OR, odds ratio; SHS, Scottish Household Survey; UK, United Kingdom; UL, upper level


There have been numerous attempts to synthesize the results of local‐scale biodiversity change studies, yet several geographic data gaps exist. These data gaps have hindered ecologist's ability to make strong conclusions about how local‐scale species richness is changing around the globe. Research on four of the major drivers of global change is unevenly distributed across the Earth's biomes. Here, we use a dataset of 638 anthropogenically driven species richness change studies to identify where data gaps exist across the Earth's terrestrial biomes based on land area, future change in drivers, and the impact of drivers on biodiversity, and make recommendations for where future studies should focus their efforts. Across all drivers of change, the temperate broadleaf and mixed forests and the tropical moist broadleaf forests are the best studied. The biome–driver combinations we have identified as most critical in terms of where local‐scale species richness change studies are lacking include the following: land‐use change studies in tropical and temperate coniferous forests, species invasion and nutrient addition studies in the boreal forest, and warming studies in the boreal forest and tropics. Gaining more information on the local‐scale effects of the specific human drivers of change in these biomes will allow for better predictions of how human activity impacts species richness around the globe. It is well recognized that the Earth's biodiversity is undergoing significant change resulting from various types of human activity . Studies that reported multiple measures of species richness for the same geographic location  were only included in the dataset once and the values were averaged when calculating effect sizes. We only included multiple responses from the same study when they were taken from different countries or biomes. The selection criterion is similar to that in Murphy and Romanuk  and a moTo investigate the data gaps existing across the Earth's biomes, we categorized study responses using the 14 global terrestrial ecoregions identified by Olson et al. . We visuP‐value was equal to or less than 0.05.We conducted a separate chi‐squared test for each driver of change and used the total number of studies for each driver to calculate the expected number of studies. For example, the total number of land‐use change studies across all biomes is 342; therefore, to calculate the expected number of studies in each biome for the chi‐squared test based on land area, we multiplied the proportion of land area that each biome covers by 342 to give the expected values. These values were then compared to the observed number of studies in each biome in the chi‐squared test. Biome–driver combinations were considered significantly over‐ or under‐represented if the c) and impacted (i) treatments in each study and was calculated as the response ratio , while the Nearctic and Oceanic realms are significantly over‐represented . Based on land area, land‐use change studies are significantly over‐represented in the Neotropics  and are significantly under‐represented in the Palearctic . Both species invasion and nutrient addition studies are significantly under‐represented in the Afrotropics  and significantly over‐represented in the Nearctic and Oceanic  realms. Warming studies are significantly over‐represented in the Nearctic realm .Our results reveal several biases in the global distribution of anthropogenically driven, local‐scale species richness change studies. Studies included in the dataset were conducted in 79 countries. The five countries with the greatest number of responses were as follows: USA (23.6% of responses), China (8.1% of responses), Brazil (6.5% of responses), Canada (5% of responses), and Australia (3.7% of responses). The Palearctic and Nearctic are the most commonly studied biogeographic realms with 33.8% and 28.6% of studies conducted in these realms, respectively. Across all studies, the Afrotropic and Antarctic realms are significantly under‐represented based on land area , while the temperate broadleaf and mixed forest, temperate coniferous forest, tropical moist broadleaf forest and Mediterranean biomes are significantly over‐represented .Across all drivers, temperate broadleaf and mixed forests 31%) and tropical moist broadleaf forests 23%) are the most frequently studied biomes , and over two times, the number of expected responses in the temperate broadleaf and mixed forest . All other biomes contain less than 6% of the land‐use change studies . When analyzed based on the projection of future land‐use change and the impact that land‐use change has on the biodiversity of each biome, the tropical moist broadleaf forest remains over‐represented in both categories . The temperate broadleaf and mixed forest biome is over‐represented based on the impact on biodiversity , but not based on projected future land‐use change. Both the temperate and tropical coniferous forest biomes are significantly under‐represented based on the magnitude of land‐use change expected to occur in these biomes in the future , and the tropical coniferous forest is almost significantly under‐represented based on the impact to biodiversity . The temperate grassland and tropical dry forest biomes have the lowest variance in the magnitude of species richness change following land‐use change , while the desert and tropical coniferous forest biomes have the highest variance  .There is notable disparity in how frequently studied a biome is when the four drivers of change are examined separately Figs. , 2. One P < 0.001, df = 12; 18%), but not based on the projected extent of exotic invasions and the impact of invaders on Mediterranean biodiversity. Invasion studies are relatively well represented in temperate grasslands, deserts, and tropical moist broadleaf forests, yet all other terrestrial biomes contain 5% or fewer of the invasive species responses , while the temperate broadleaf forest , temperate grassland , and Mediterranean  biomes have the highest variance .Studies that examine the effect of species invasions on local‐scale species richness change are significantly over‐represented in the temperate broadleaf and mixed forests  based on all three categories , but temperate broadleaf and mixed forests are the only biome that is significantly over‐represented based on the projected levels of future nutrient addition and the impact on biodiversity (Table n = 2), temperate grassland , and tundra  biomes have the lowest variance in the magnitude of species richness change following nutrient addition, while the tropical moist forest  and boreal forest  biomes have the highest variance .Over half of nutrient addition studies are conducted in the temperate region Fig. , Table 1P < 0.001, df = 12; 39% of studies). Warming studies are also well represented in the tundra biome (23%), yet are lacking in the boreal forest (5%) and nonexistent in the tropics with zero warming studies conducted in tropical grasslands and the three tropical forest biomes  and temperate broadleaf forest  biomes have the lowest variance in the magnitude of species richness change following warming, while the montane grassland  and tundra  biomes have the highest variance .Similar to the other drivers, warming studies are over‐represented in temperate broadleaf and mixed forests based on land area, projections of future change, and impact on biodiversity  and the Mediterranean (18% of responses). Invasions by exotic species are most likely in regions of high human activity  compared with the large number of total studies conducted in this biome. Species invasions are not thought to be one of the major threats to biodiversity in the tropical biomes as the high diversity in the tropics minimizes the chance of non‐native species successfully invading  and are better represented in the tundra biome compared with the other four drivers of change (23% of responses). Global circulation models predict larger increases in temperature at higher latitudes  in the magnitude of change in species richness following the four human drivers of change.Click here for additional data file. Click here for additional data file.


Adolescence [defined by the World Health Organization (WHO) as the time period between the ages of 10 and 19 years] is a critical period in human physical and psychosocial development when an individual progresses from an immature state to a mature state capable of reproduction. Pregnancies in this stage of life account for 23% of the burden of disease arising from pregnancy and childbirth, despite only representing 11% of all births worldwide.BJOG published an issue last year on the WHO Multicountry Survey of Maternal and Newborn Health, in which the authors of one paper reported higher rates of various pregnancy and childbirth outcomes (including low birthweight) in adolescents aged 10–19 years, compared with young adults aged 20–24 years, and concluded that ‘interventions are crucial to reduce adverse pregnancy outcomes among adolescent women in LMICs’.Ninety‐five percent of the 16 million adolescent pregnancies that occur each year are in low‐ and middle‐income countries (LMICs),Physical size (e.g. weight and height) is an indicator of nutritional status, and the odds of SGA are increased in adult women with pre‐pregnancy height [odds ratio (OR) 1.9] or weight OR 2.5) in the lowest, compared with the highest, quartile..5 in theStudies in Bangladesh and Mexico have suggested that adolescent girls  stop growing in response to pregnancy: the change in height  was approximately zero in pregnant adolescent girls, but was positive and significant in non‐pregnant adolescent girls matched on age and menarcheal age.The two prominent adolescent pregnancy nutrient‐partitioning studies that have investigated offspring outcomes were conducted in high‐income countries (HICs).A recent publication of the Consortium of Health Orientated Research in Transitioning Societies group found that adolescent pregnancy (ages ≤ 19 years), compared to young‐adulthood pregnancy (ages 20–24 years), was associated with increased risk of stunting at age 2 years (OR 1.46) and higher adulthood fasting glucose concentrations in the offspring.Six studies were identified that had supplemented the diet of pregnant adolescents and measured growth and development‐related outcomes. Two of these studies involved calcium supplementation,As is clear, the literature on the nutritionally mediated pathways underpinning the links between young maternal age and poor intergenerational and long‐term health is sparse. Existing publications have studied different age ranges, without equal distribution of adolescents across those age ranges, which combined with other between‐study differences (e.g. parity) has contributed to largely equivocal findings. Evidence of nutrient partitioning is mostly limited to a few studies in HICs, where the nutritional requirements of adolescence and pregnancy are likely to be met. Two studies in LMICs suggest that adolescent girls stop growing in response to pregnancy,To understand which (and how and when) components of nutrition increase risk for adverse outcomes in the offspring of adolescent compared to young‐adulthood pregnancies, a prospective observational study with a young‐adult reference group is required; recruitment of equal numbers of females in each yearly age band between 13 and 26 years would provide an adolescent group and a young‐adult group, and allow in‐depth investigation of difference within these groups. Furthermore, to understand which components of nutrition increase risk for adverse outcomes in the adolescents themselves (and how and when), a non‐pregnant reference group matched on key variables  is also required. The females and their offspring would ideally be followed‐up for long‐term health assessment and subsequent pregnancies. Such a study would be best suited to LMICs where rates of adolescent pregnancy and their adverse sequelae are high. Preferably, a multicentre programme of research across contrasting environments (in the same country or in different countries) would be conducted in order to understand how the nutritional epidemiology of adolescent pregnancy might depend on context (e.g. the disease profile of the population being studied). This will enable any subsequent nutritional intervention to be appropriately tailored. Careful consideration of the context of adolescent pregnancy within each setting would also be necessary to understand the role of socio‐economic position in influencing both the probability of an adolescent becoming pregnant and (via nutrition and other factors) the risk of adverse outcomes.Although the WHO recommend pregnancy prevention as the primary solution for poor reproductive outcomes of adolescent pregnancy, societal and cultural practices in many LMICs are a barrier to changes in practice.None declared. Completed disclosure of interests form available to view online as supporting information.WJ and SEM conceptualized the commentary, drafted and revised the article critically for important intellectual content, approved the version to be published, and agree to be accountable for all aspects of the work.Not applicable.WJ and SEM are funded by the Medical Research Council (UK) programme: MC_UP_1005/1. Click here for additional data file. Click here for additional data file.


Previous studies have demonstrated a correlation between medical students who undertake international medical electives (IMEs) in resource poor settings and their reported career preference for primary care in underserved areas such as rural practice. This study examines whether a similar correlation exists in the Australian medical school context.Data was extracted from the Medical Schools Outcomes Database (MSOD) of Australian medical students that completed commencing student and exit questionnaires between 2006 and 2011. Student responses were categorized according to preferred training program and preferred region of practice at commencement. The reported preferences at exit of students completing IMEs in low and middle income countries (LMIC) were compared to those completing electives in high income countries (HIC).The effect of elective experience for students expressing a preference for primary care at commencement was non-significant, with 40.32 % of LMIC and 42.11 % of HIC students maintaining a preference for primary care. Similarly there were no significant changes following LMIC electives for students expressing a preference for specialist training at commencement with 11.81 % of LMIC and 10.23 % of HIC students preferring primary care at exit. The effect of elective experience for students expressing a preference for rural practice at commencement was non-significant, with 41.51 % of LMIC and 49.09 % of HIC students preferring rural practice at exit. Similarly there were no significant changes following LMIC electives for students expressing a preference for urban practice at commencement, with 7.84 % of LMIC and 6.70 % of HIC students preferring rural practice at exit.This study did not demonstrate an association between elective experience in resource poor settings and a preference for primary care or rural practice. This suggests that the previously observed correlation between LMIC electives and interest in primary care in disadvantaged communities is likely dependent on student and elective program characteristics and supports the need for further research and critical examination of elective programs at Australian medical schools. Student interest in international medical electives (IMEs) has prompted researchers to evaluate their educational potential and role in medical curricula . A recenThe best evidence for this association is published in several US-based single institution comparative studies. For example, Ramsey and colleagues found that 36 % of doctors participating in an IME program in a low income country as medical students chose general practice compared to 11 % of controls . SimilarDespite including suitable control groups, caution must be exercised when interpreting the results of these studies as: (i) none used longitudinal data to evaluate changes in career preferences before and after elective experiences; (ii) all of the programs included applicant selection processes that likely generated a significant selection bias; and (iii) these studies focus on individual, well structured, and supported elective programs. As acknowledged by all authors, these limitations make it impossible to infer causality or generalize beyond the participating students and doctors.This study responds to these limitations and evaluates the transferability of previous findings to the Australian context. Specifically, we analysed questionnaire data collected by the Medical School Outcomes Database (MSOD). These questionnaires are offered to all students enrolled in Australian medical schools and are administered at commencement of studies and at graduation. Consequently, this study provides a novel analysis of career preference before and after elective experience using a large and representative sample.MSOD is the principal data collection project for medical student information in Australia, implemented and operated by the Medical Deans of Australia and New Zealand to evaluate educational programs and inform workforce planning. Questionnaire data are collected directly from medical students from all 18 medical schools in Australia . StudentData from MSOD were provided to the authors in May 2013, and included elective data and selected questionnaire data for students completing both the Commencing Medical Student Questionnaire (CMSQ) and Exit Questionnaire (EQ) during the period, 2006–2011 , 10. Thin = 3673). We assumed that international students completing electives in their country of birth likely had systematically different motivations for undertaking IMEs and were excluded from the analysis, resulting in a total study cohort of n = 3596.Only students responding to either question of interest (see n = 212), low and middle income country electives were not stratified.Students were categorized as having completed at least one overseas elective in a low or middle income country (LMIC) setting, or as having completed electives only in high income country (HIC) settings, which included electives completed in Australia or overseas. Host countries were categorized as LMIC if they reported a gross national income (GNI) less than US$12 275 in the World Development Index . Due to Two streams of analysis were conducted to examine, i) the association between elective experience and preferred training program at EQ taking into account CMSQ preference and, ii) the association between elective experience and preferred region of practice.n = 2213). Students reporting their decision as not final at EQ were categorized according to the first of their top three preferences. Respondents’ preference at CMSQ was treated as a confounder and respondents were categorized accordingly, resulting in CMSQ preference categories for primary care (n = 309), specialist (n = 1508), and undecided (n = 396). The preferences reported at EQ for students that completed LMIC electives were compared to those that completed HIC electives. The association was tested using Chi Square.The CMSQ and EQ asked students to select from a range of responses for preferred training program. Preferences were categorized into “primary care” when respondents indicated a preference for general practice, public health medicine, or rural and remote medicine, or “specialist”, for all other preferences. Only students that provided answers for the preferred training program question at CMSQ and EQ were included (n = 2894). Again, respondents’ preference at CMSQ was treated as a confounder and CMSQ preference categories were created for rural (n = 656) and urban (n = 2238). The preferences reported at EQ for students that completed LMIC electives were compared to those that completed HIC electives for both categories. The association was tested using Chi Square.There were no questions in the CMSQ or EQ that asked specifically about work with underserved populations. Rural practice was accepted as a surrogate because rural populations are one of the largest and most visibly underserved populations in Australia. The questionnaires asked students to select from a range of responses for preferred region of practice. Preferences were categorized as “rural” if respondents indicated preference for a regional city, large town, small community, and smaller town or “urban” if they indicated preference for a capital city or major urban centre. Only students that provided answers for the preferred region of practice question at CMSQ and EQ were included .χ2 = 0.065, df = 1, p = 0.80), specialty , and undecided .The results for preferred training program can be found in Table χ2 = 2.781, df = 1, p = 0.10) and urban .The results for preferred region of practice can be found in Table This study evaluated data provided by MSOD for a relationship between elective experience in resource poor settings and student career preferences for primary care and work with underserved populations. This analysis did not detect any association between elective experience and career preferences.The lack of a statistically significant correlation in these data must be interpreted carefully, as failing to find a significant correlation is not the same as demonstrating that it does not exist . HoweverFirst, previous studies used selection criteria that likely recruited participants with systematically distinct motivations and career intentions that may have caused selection bias. For example, the elective program studied by Godkin and Savageau required students to submit a written application and essay . The IntIn contrast, the MSOD data were collected from students from across Australia, many of whom arranged electives independently. It is reasonable to infer that this population has diverse motivations for completing electives in LMIC settings. A recent literature review provides insight into what motivates medical students to undertake IMEs. It identified three dominant motivations: (i) altruism; (ii) self-serving rationale, such as language acquisition, exposure to range of illnesses, or access to high patient volumes; and (iii) the opportunity to work beyond the scope of practice typically allowed for medical students . ElectivSecond, the present findings may reflect differences in the electives themselves. Elective programs studied previously tended to include student support and structured learning outcomes. For example, participants in the study reported by Ramsey and colleagues were required to complete a two week full-time course prior to departure and were expected to participate in community health activities as well as clinical placements , 17. AlsIn contrast, Australian students often organize electives independently and receive limited and variable support and structure. In a recent study, 12 of the 16 medical schools interviewed in Australia reported that they offered pre-departure training, but only half of those programs were mandatory and had an average duration less than five hours .The contribution of these two key differences to understanding the disparity between past and present findings is offered tentatively and subject to confirmation through further research. Subject to this limitation, these findings suggest that the previously established association between elective experience and career preference may be limited to well-structured and supported elective programs that accept students with specific motivations.It is worth noting that the students and programs previously studied aspire to the recommendations for safe and educational elective programs described in the literature –25. SpecWhile Australian medical students are likely to benefit from the electives that they undertake, the differences in program characteristics invite the question; does this disparity in results reflect substandard structure and support for Australian medical students undertaking electives in resource poor settings to the detriment of student wellbeing, learning, and professional growth? At the very least, these findings establish the need for further research into ways to minimize risk and maximize learning and hopefully encourage medical educators to critically examine the elective programs for which they are responsible.There are important limitations to this study. First, due to limitations inherent to secondary analysis of data, the analysis employed national GNI as a relatively crude indicator of resource poor elective setting. Inevitably there is considerable within- and between-country variation in terms of healthcare resource allocation. Visiting a LMIC does not guarantee exposure to the kind of resource poor settings previously studied.n = 1383) compared to location of practice (n = 702). This finding is consistent with survey results published on the MSOD website, however the reason for the consistently poorer response rate to the specialty of practice question is unknown [Second, there is a large discrepancy between respondent attrition from CMSQ to EQ for speciality of practice  the motivations and characteristics of Australian medical students to undertake IMEs; and ii) how to best structure electives and support students to maximise student learning and safety, while maintaining the integrity of host community healthcare.


Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio‐based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more  directed manipulations of metabolism.Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non‐native host is considered. The advantages of a particular oilseed crop,  Camelina sativa as a useful platform for metabolic engineering of lipids, and propose that a new paradigm of predictive manipulation will exceed progress made thus far with iterative approaches.In this review we advance the oilseed plant  Plant seeds are a reservoir of energy‐dense molecules, including oils enriched in triacylglycerols (TAGs) that serve as the primary storage form of fatty acids. These TAGs and their component fatty acids not only provide a major dietary calorie source and media for food preparation, but also serve as a renewable source of hydrocarbons for biofuels and industrial applications. Although our knowledge of plant lipid metabolism and its regulation is not complete, the basic pathways of fatty acid biosynthesis, modification and assembly into triacylglycerols are well characterized. With this information and the wealth of genetic diversity for synthesis of novel fatty acids and storage oils, seeds offer a ‘palette’ and platform for the design and tailoring of biochemical pathways to generate diverse nutritional and industrial oils not currently found in oilseed crops. As tools for synthetic biology and information from large‐scale systems biology studies emerge, it is possible to rapidly assemble novel pathways in oilseed crops and achieve predictable outcomes.Camelina sativa is both a model system and a crop platform for lipid metabolic engineering because of its close genetic relation to Arabidopsis (both being members of the family Brassicaceae), its simple, non‐labour‐intensive transformation system and its relatively short life cycle.For the purpose of this review, synthetic biology will be defined as the design and engineering of biologically based parts and novel activities to facilitate the redesign of existing, natural biological systems. The application of synthetic biology for metabolic engineering of plants has lagged behind synthetic biology‐based engineering of microbial systems due in part to the challenges and long time‐frames associated with obtaining transgenic plants and the imprecision and lack of predictability associated with random insertion of transgenes into the host plant genome. However, seed lipid metabolism represents a good system for building and developing synthetic biology tools for metabolic engineering because lipid biosynthetic pathways are generally well characterized, analytical protocols exist for rapid measurement of fatty acid and lipid products and lipidomic methodologies are available to assess global changes in lipid and biosynthetic intermediates for iterative improvement of engineering strategies. Concomitantly an oilseed chassis has emerged that is capable of hosting the new functions necessary to manufacture novel molecules. The oilseed plant C. sativa as a platform for the production of bioproducts, outline the metabolic context and then, through a series of case studies, examine how lipid synthesis in seed oils can be redesigned to enable the accumulation of novel fatty acids that have beneficial functional groups or properties.The fatty acid and lipid biosynthetic pathways of plants form a biochemical chassis upon which strategies for the production of novel molecules can be synthetically designed. Although questions about the regulation and biochemical architecture of enzymes in these pathways remain, the basic framework of fatty acid and lipid biosynthesis in plants is well characterized. New enzymes can be introduced from other species or rationally designed to alter carbon flux through these pathways, producing compounds of high value that are absent or typically found in low levels in oilseed crops. The aim of this review is to discuss the emergence of C. sativa), an oilseed crop of the Brassicaceae, has been identified as a promising new crop for oil production due to its adaptability to temperate growing regions, low input requirements, a short crop cycle and disease resistance  and an oil content of about 40%  and linoleic acid (18:2)  and low in erucic acid (22:1), a fatty acid that has been linked to heart disease  the ease with which it can be transformed via Agrobacterium floral vacuum infiltration . The DAG is then available for two different acyltransferase reactions: diacylglycerol acyltransferases (DGAT) transfer acyl‐CoAs to the sn‐3 position of DAG to produce TAG; alternatively phospholipid:diacylglycerol acyltransferases (PDAT) transfer the sn‐2 acyl group of from phospholipids to DAG, forming TAG  and linoleic  acids. Using the ‘omega’ nomenclature for unsaturated fatty acids, in which the position of the double bond is determined by counting carbon atoms starting from the methyl end of the acyl chain, the Δ9 double bond of these C18 fatty acids is at the omega‐9 position. This double bond is formed by the activity of the soluble, plastid‐localized Δ9 acyl‐acyl carrier protein (ACP) desaturase, which is most active with stearoyl (18:0)‐ACP  rather than omega‐9 unsaturated fatty acids (e.g. 18:1Δ9) provided the basis for the recently reported redesign of unsaturated fatty acid biosynthesis in C. sativa seeds for the production of oils containing up to 60% omega‐7 mononunsaturated fatty acids  with improved kinetic properties with the 16:0‐ACP substrate  suppression of KASII further increased amounts of these fatty acids to about 40% of the total fatty acids , resulting in the accumulation of primarily 16:1Δ9 and 18:1Δ11. Overall, this strategy illustrates how fatty acid synthesis and modification reactions can be tailored and iteratively optimized around a synthetic fatty acid desaturase for the redesign of unsaturated fatty acid synthesis to produce compounds of industrial value.The design of a Δ9‐16:0‐ACP desaturase to produce omega‐7 unsaturated fatty acids (e.g. 16:1Δrase ‘Com5’ with iSimmondsia chinensis) seeds  seeds . The latter storage form, referred to as acTAG, is similar to TAG except that acetate (C2) is present at the sn‐3 position of TAG instead of a fatty acid   and reduced in polyunsaturated fatty acids for improved oxidative stability of acTAG oil  and α‐linolenic acid  to omega‐3 long‐chain polyunsaturated fatty acids (LC‐PUFA) like eicosapentaenoic acid  and/or docosahexaenoic acid  requires the introduction and coordinated expression of multiple transgenes. Two separate and converging aerobic routes have been identified for the biosynthesis of the C20 LC‐PUFAs arachidonic acid  and EPA . Analysis of the lipids in the seeds and leaves of the transgenic plants confirmed the production of moderate levels of EPA but also high levels of C18 Δ6 desaturation products, e.g. γ‐linolenic acid  and stearidonic acid . Following these two studies many researchers undertook an iterative engineering approach  and Napier et al. (Rothamsted Research), was to directly assess gene combinations and their regulatory elements in the seeds of stably transformed plants  the feasibility of producing omega‐3 LC‐PUFAs in the field without any yield penalty  industry. Perhaps counter‐intuitively, marine and salmonid fish species have a very limited capacity to synthesize EPA and DHA and consequently the human nutritional value of the finished product is determined by the diets provided to the farmed fish. To produce the very significant volumes of omega‐3 LC‐PUFAs required by aquaculture necessitates the production of EPA and DHA in agricultural oilseed crops rather than via algal fermentation. The opportunities of scale associated with such crops provide the only economically viable route to generate a fish oil substitute  in the required quantities. As an established oilseed crop, C. sativa variety, enzyme specificity, constructs design/orientation and possibly the site of integration influence outcomes. For example, the choice of Δ5‐elongase defined the extent of EPA accumulation; a highly active Δ5‐elongase will generate DHA at the expense of EPA  suggested that the maximum levels of EPA accumulation in seeds were about 8%, whereas in C. sativa levels of about 24% were observed  characterization of the lipid synthesis and assembly network, (ii) the coordinated and targeted expression of multiple genes and functional activities in specific tissue types (compartments), (iii) the assembly of complex transgene cassettes and their targeted insertion into the genome of the host plant, and (iv) the rational design of new synthetic enzyme activities.It is clear from each of the examples above that tools are available for the predictable and reliable synthetic design of seed lipid metabolism. The success of these approaches has required the coordinated and targeted expression of multiple genes and the optimization of enzyme activities. The availability of a adaptable chassis like et al., et al., Although significant progress has been made in both the synthesis and accumulation of target compounds, identification of key genes associated with lipid synthesis remains elusive. As discussed, many of the enzymes involved in the synthesis and modification of fatty acids and their assembly into TAGs have been well studied and are conserved between most of the major oilseed species. However, comparatively little is known about the genes and assembly of pathways that produce the extensive variation in seed oil composition seen in nature. Even in plants with complete genome sequences, it is difficult to identify all the components of complex lipid metabolic pathways. For example, the use of genome‐wide association studies (GWAS) in Arabidopsis has recently identified new genes associated with lipid synthesis and composition  in seeds. Codon‐optimization, directed evolution, screening enzyme libraries and the incorporation of non‐natural amino acids all provide ways of improving or generating novel enzymatic activities. These approaches have the potential to produce long‐lasting re‐engineered enzymes with specific properties necessary for versatile bio‐production  enzyme activities, e.g. an improved DGAT for the incorporation of EPA/DHA‐CoA into TAG. The discussion above demonstrates the utility of designing a Δ9‐16:0‐ACP desaturase to produce omega‐7 unsaturated fatty acids  to deliver a step change in crop performance and lower the environmental impact of agriculture Figure . Such anin silico. Ultimately, a combination of ‘omic technologies, together with new genome editing capabilities will greatly expand our ability to alter the metabolism of any given chassis. However, the real goal is to deliver such modifications in such a manner that is predictive (and not require multiple iterations), ideally based on computational, rather than biological, interrogation of the system. Even in the intensively studied area of plant seed metabolism, this objective is still some way off, but the examples described in this article demonstrate not only considerable progress but also areas for future study.There are now several successful examples of complex metabolic engineering of oilseeds for a range of useful and valuable traits. In some cases, the engineered plants have undergone field‐trial evaluation, and shown promising stability of the introduced trait under ‘real world’ conditions. Much of this progress has been achieved through a combination of intuitive interventions and several rounds of iteration, in which ‘learning by doing’ plays a critical role. In that respect, a transition to more predicative approaches is both desirable and essential, and new methodologies to further understand the endogenous metabolism, with which transgene‐directed activities must integrate, will provide the underpinning knowledge base by which better interventions might be designed


The expansion of oil palm plantations at the expense of tropical forests is causing declines in many species and altering ecosystem functions. Maintaining forest‐dependent species and processes in these landscapes may therefore limit the negative impacts of this economically important industry. Protecting riparian vegetation may be one such opportunity; forest buffer strips are commonly protected for hydrological reasons, but can also conserve functionally important taxa and the processes they support.We surveyed leaf litter ant communities within oil palm‐dominated landscapes in Sabah, Malaysia, using protein baits. As the scavenging activity of ants influences important ecological characteristics such as nutrient cycling and soil structure, we quantified species‐specific rates of bait removal to examine how this process may change across land uses and establish which changes in community structure underlie observed shifts in activity.Riparian reserves had similar ant species richness, community composition and scavenging rates to nearby continuous logged forest. Reserve width and vegetation structure did not affect ant species richness significantly. However, the number of foraging individuals decreased with increasing reserve width, and scavenging rate increased with vegetation complexity.Oil palm ant communities were characterized by significantly lower species richness than logged forest and riparian reserves and also by altered community composition and reduced scavenging rates.Reduced scavenging activity in oil palm was not explained by a reduction in ant species richness, nor by replacement of forest ant species by those with lower per species scavenging rates. There was also no significant effect of land use on the scavenging activity of the forest species that persisted in oil palm. Rather, changes in scavenging activity were best explained by a reduction in the mean rate of bait removal per individual ant across all species in the community.Synthesis and applications. Our results suggest that riparian reserves are comparable to areas of logged forest in terms of ant community composition and ant‐mediated scavenging. Hence, in addition to protecting large continuous areas of primary and logged forest, maintaining riparian reserves is a successful strategy for conserving leaf litter ants and their scavenging activities in tropical agricultural landscapes. Our results suggest that riparian reserves are comparable to areas of logged forest in terms of ant community composition and ant‐mediated scavenging. Hence, in addition to protecting large continuous areas of primary and logged forest, maintaining riparian reserves is a successful strategy for conserving leaf litter ants and their scavenging activities in tropical agricultural landscapes. Agricultural expansion and intensification continue to cause widespread loss of biodiversity and alter ecosystem functioning. In tropical regions, oil palm is among the most rapidly expanding crops, especially in South‐East Asia  affect ant communities and scavenging rates?2 area of twice‐logged lowland dipterocarp rain forest, acacia plantation Acacia mangium and oil palm plantation Elaeis guineensis (planted between 1998 and 2012) in Sabah, Malaysian Borneo . Sampling was conducted in the continuous twice‐logged forest (n = 8 sites/streams) in which selective logging had been carried out in the 1970s and 1990s – 2000s  and at sites adjacent to rivers in oil palm without a riparian reserve . There is no primary forest within 50 km of these sites, and as riparian reserves are isolated linear fragments in a previously logged and then converted landscape, riparian zones in continuous logged forest are an appropriate comparison. All data were collected between April and July, the relatively dry half of the year  within a 600‐km. et al. . The meaAt each sampling point, we carried out a 30‐min observation of scavenging activity. In both years, all observations at each site were carried out in 1 day. Baits were pellets made of crushed earthworm . Bait platforms of laminated graph paper were placed with the edge flush with the soil. Each had thirty baits, one placed in the centre of every 2 × 2 cm square . We used four different size classes, randomly positioned on the grid for each trial  to ensure that baits were attractive to a range of ant species and similar to naturally occurring sources of protein (e.g. dead invertebrates).We recorded the time when the first ant entered the bait card and the number of individuals arriving during each five‐minute time period. We recorded temperature at the beginning of each trial as this can affect foraging activity  and tree basal area using the angle point method  species count, the number of species arriving at each bait card; and (iv) species richness, the number of species observed across all observations at each site. As we were only able to complete 12 (of 15) observations at two of the 25 sites, we calculated the incidences of each species and then applied a coverage‐based richness estimation technique using the iNEXT online platform  ant abundance, the total number of foragers arriving at each observation. There were 15 observations in which all bait items were removed before the trial ended, causing subsequent declines in ant abundance. We corrected for this by assuming that ant abundance would have remained at the level observed during the five‐minute period before the last bait item was removed; (ii) ant diversityWe also calculated functional metrics for each observation: (i) time until the first ant reached the bait card, (ii) number of bait pellets removed, (iii) the proportion of bait mass removed and (iv) recruitment rate. We calculated recruitment rate by extracting the gradient of a linear regression on the number of ants arriving in each 5‐min time period following arrival of the first ant.et al. We analysed the effect of land use, temperature and their interaction on each of our community and functional metrics. For abundance of ants, diversity of ants, time until the first ant arrived, number of bait pieces removed, proportion of bait mass removed and recruitment rate, we ran generalized linear mixed models (GLMMs). We set site as a random factor and specified transformations and error families as appropriate see . For sitThere are three non‐mutually exclusive hypotheses for the mechanisms underlying changes in scavenging activity following habitat conversion: (i) that species are lost (and not replaced) when habitats are converted and that this results in reduced bait removal; (ii) that there is turnover in species composition with habitat conversion, and the new species scavenge at a different rate due to a) changes in forager density, b) new species having different scavenging rates to those they replace or c) changes in scavenging rates per forager resulting from increased numerical dominance of species that remove baits relatively slowly; and (iii) that persisting (shared) species alter their scavenging activity in converted habitats  changes in the density of foragers, b) changes in the species scavenging activity or c) changes in the numerical dominance of species with different scavenging rates).To examine whether loss of species explained the observed differences in bait removal (hypothesis 1), we ran a generalized linear model to test for a relationship between the proportion of bait removed  and species richness, using data from all sites.We then tested whether turnover in species could explain differences in bait removal. To ensure that we were only testing for differences between the ant communities responsible for the observed differences in scavenging rates, we combined data from land uses with no significant differences in both ant community composition and overall bait removal rates. We then isolated data for the species that were unique to each group (i.e. the species ‘replaced’ in the change from land use(s) with higher scavenging rates to land use(s) with lower scavenging activity) and tested whether the abundance of foragers differed between these two groups (hypothesis 2 a). To see whether species unique to land uses with less overall scavenging had lower per individual bait removal rates than those they had ‘replaced’ (hypothesis 2 b), we calculated each species’ scavenging rate . We then tested whether the species’ scavenging rates differed between our land‐use groupings. We also calculated the mean bait removal rate per ant  and tested whether this differed between species unique to the land uses with high and low rates of scavenging (hypothesis 2 c).To investigate whether observed differences in scavenging activity could be explained by changes in the persisting species, we first isolated the data on the subset of species found in land uses with both high and low rates of scavenging. We then tested whether the abundance (hypothesis 3 a) and bait removal rate (hypothesis 3 b) of these shared species differed between the land uses. We also tested whether the mean bait removal rate per forager (hypothesis 3 c) differed between land uses.permanova, respectively, with the mean width for each site, the mean vegetation complexity and their interaction as predictors. All analyses were carried out in R . Ant abundance declined significantly with increasing riparian strip width, but there were no other significant relationships between reserve width or habitat complexity and the number of species at each observation, the diversity of ants or the site‐level species richness  could be because ground cover is necessary for foraging ants to risk carrying baits that reduce their speed and increase their vulnerability to predators. As there was no effect of reserve width on species richness or scavenging rate, we conclude that widths similar to those in this study can conserve leaf litter ant fauna that would be lost if oil palm was planted up to the river bank. We also conclude that riparian reserves can maintain the ant communities, functional role as scavengers . However, the composition of the wider reserves was more similar to the twice‐logged forest areas Fig. , and so et al. et al. Although we have demonstrated that riparian reserves retain leaf litter ant communities similar to those in larger areas of twice‐logged forest, other aspects of reserve design deserve further attention. We were not able to assess the importance of corridor connectivity, as all the riparian reserves we surveyed were linked to large fragments of logged forest (>3000 ha). Other studies in tropical landscapes have shown that the connectivity to large areas of forest can be crucial for the persistence of some species (Laurance & Laurance Protection of riparian forest can help retain biodiversity and ecological functions within tropical agricultural systems. Our results indicate that the ground‐foraging ant fauna is less diverse in oil palm plantations than nearby forest and that scavenging activity is also impaired; this may have implications for food webs and nutrient cycling in the plantations. Our data suggest that the reduction in scavenging is best explained by increases in the relative abundances of species with low bait removal rates. In contrast, neither the ant communities nor their scavenging activity differed between continuous logged forest and forest in riparian reserves. Hence, we conclude that protecting riparian reserves can help mitigate the negative impacts of oil palm expansion on tropical biodiversity and ecosystem function.Fig. S1. Map of study sitesTable S1. Names of all species observed and the number of foragers counted across all observations in each land use.Click here for additional data file.


IPMN) of the pancreas is characterized by intraductal papillary proliferation of mucin‐producing epithelial cells that exhibit various degrees of dysplasia. IPMN is classified into four histological subtypes  according to its histomorphological and immunohistochemical characteristics. Endoscopic retrograde cholangiopancreatography plays a crucial role in the evaluation of these features of IPMN. Endoscopic ultrasonography (EUS) has proven to be more sensitive than computed tomography or magnetic resonance imaging for early detection of malignancy. The present review addresses the current roles of endoscopy and related techniques in the management of IPMN. The particular focus is on diagnosing IPMN and malignancy within IPMN, detecting pancreatic cancer concomitant with IPMN, differentiating the epithelial subtypes of IPMN, determining the optimal strategy for the management of branch duct IPMN, and discussing innovative endoscopic technology related to IPMN. The disadvantages of endoscopic examinations of IPMN and different attitudes toward EUS‐guided fine‐needle aspiration for IPMN between Japan (negative) and other countries (active) are also discussed.Intraductal papillary mucinous neoplasm ( The macroscopic morphology is divided into three types: main duct type (MD‐IPMN), branch duct type (BD‐IPMN), and mixed type.The international consensus guidelines for the management of IPMN, as revised by the International Association of Pancreatology in 2012, do not recommend endoscopic retrograde cholangiopancreatography (ERCP) as a routine examination for sampling of fluid or brushings in IPMN. Thus, it is considered a special examination to be carried out only in the context of research.The threshold of the main pancreatic duct (MPD) diameter for suspicion of MD‐IPMN has been lowered to 5 mm to increase the sensitivity of the diagnosis without jeopardizing the specificity.One of the specific features of BD‐IPMN is the presence of communication with the MPD, which is not a common feature of mucinous cystic neoplasm. However, the accumulation of mucus within the BD‐IPMN and its communicating branch frequently hampers the demonstration of the communication, even by ERCP. Instead, ERCP often reveals mucus moving within the MPD and changing its shape. The presence of mucus as shown by ERCP is regarded as a confirmatory finding of IPMN. EUS is often useful to demonstrate communication between the BD‐IPMN and MPD, even when occluded by mucus.Cytology is the gold standard examination technique for diagnosis of malignancy in IPMN. Cytological examination can be done using pancreatic juice obtained during ERCP or cyst fluid sampled by EUS‐guided fine‐needle aspiration (EUS‐FNA). Both of these approaches have advantages and disadvantages Table .Cytology of the pancreatic juice is associated with relatively low sensitivity of 10–50% for diagnosing malignancy Table  .6, 7, 8et al.Cyst fluid obtained by EUS‐FNA can also be used to diagnose malignant BD‐IPMN with a reported sensitivity and specificity of 67% and 88%, respectively, at a special institution with expertise in FNA and sophisticated cytodiagnostic interpretation.et al.et al.EUS provides several useful findings for the diagnosis of malignancy in IPMN. Mural nodules as the most significant sign of a high risk of malignancy can be clearly demonstrated by EUS. Hirono Although contrast‐enhanced power Doppler ultrasonography is associated with blooming artifacts, poor spatial resolution, low sensitivity to slow flow, and high sensitivity to motion artifacts, this new EUS system has further allowed for the observation of images of the pancreatic microcirculation and parenchymal perfusion without Doppler‐related artifacts.et al.The development of ordinary pancreatic cancer in patients with IPMN has been drawing attention during the past two decades Fig. . The firet al.More effective and efficient surveillance strategies for early detection of concomitant pancreatic cancer in patients with IPMN are needed. The intervals of the imaging surveillance proposed in the Fukuoka guidelines are now questioned because even surveillance done at 6‐month intervals may miss the diagnosis of pancreatic cancer at a sufficiently early stage.et al.GNAS mutation within codon 201. The epithelial subtypes of IPMN may be identified by ERCP cytology as described later and would help to predict the tendency of malignant transformation  and development of concomitant pancreatic cancer (mostly the gastric type).A few studies have investigated the characteristics of IPMN associated with distinct pancreatic cancer. Ideno et al.Distinct pancreatic cancer may exist in the pancreatic segment to be left in place after pancreatectomy for IPMN or pancreatic cancer concomitant with IPMN. This can be examined by preoperative ERCP cytologyFamilial pancreatic cancer provides another opportunity for the early detection of pancreatic cancer.et al.,As reported by Furukawa et al.,et al.P < 0.01) and showed a significant correlation with the rate of malignancy. Preoperative pancreatic juice cytology with MUC staining may be useful for identification of the histological subtype of IPMN.In view of these observations, it is ideal to differentiate the subtypes preoperatively to consider the surgical indication and predict the prognosis. In a preliminary study by Hibi GNAS mutational frequency.The above‐mentioned study also showed that the histological subtype is correlated with the Cyst fluid obtained by EUS‐FNA may be another useful sample for histological subtype determination. However, differentiation of histological subtypes in FNA aspirates of IPMN has not yet been investigated.The disadvantages of endoscopic examination of IPMN are shown in Table vs 4.4%, respectively; P = 0.403), Japanese endosonographers refrain from EUS‐FNA in patients with possibly malignant BD‐IPMN because of concern regarding peritoneal dissemination and gastric wall seeding secondary to cyst fluid spillage and needle track implantation of malignant cells.Disadvantages of cyst fluid analysis for the diagnosis of malignant BD‐IPMN include acute pancreatitis, bleeding, and, although rare, gastric wall seeding and peritoneal dissemination of malignant cells. Anecdotal reports have described gastric wall invasion secondary to needle track seeding, or peritoneal dissemination as a result of leakage of cyst contents through needle holes.et al.Endoscopy plays a pivotal role in decision‐making in the management of BD‐IPMN. Whether to observe or operate on a BD‐IPMN depends on the presence and size of mural nodules within the BD‐IPMN Fig. . Uehara More recent innovations in modern technology have been applied to endoscopy and contribute to the management of IPMN. First, pancreatoscopy can allow for visualization of the papillary growths of IPMN in the MPD and help to accomplish targeted sampling of neoplastic cells for cytology and biopsy.Author declares no conflict of interests for this article.


HTLV)‐1 causes T‐cell leukaemia and myelopathy. Together with HTLV‐2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother‐to‐child transmission. To provide context, we conducted a systematic review and meta‐analysis of HTLV seroprevalence in African women and children.Human T‐lymphotropic virus  in mothers and 2.2% (12/534) in children. Three mothers carried HTLV‐1 alone, seven had HTLV‐2 and one was dually infected. Three children carried HTLV‐1 alone, seven had HTLV‐2 and two were dually infected. Only two corresponding mothers of the 12 HTLV‐positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV‐1 varied from 0 to 17% and of HTLV‐2 from 0 to 4%.HTLV‐2 was higher than that of HTLV‐1 in Malawi and one of the highest for the African region. The lack of mother–child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa.In contrast to findings from other studies in Africa, the seroprevalence of  HTLV‐1 is the causative agent of aggressive adult T‐cell leukaemia/lymphoma (ATLL) and the progressive, chronic, disabling HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as other inflammatory conditions such as infective dermatitis and uveitis HTLV‐1, an oncogenic human RNA retrovirus, was discovered 35 years ago The African continent has a population over 1 billion and represents the largest endemic area for HTLV infection but with many data gaps. HTLV seroprevalence has been reported only once in Malawi, at 2.5%, when 159 blood donor sera were screened by ELISA, without typing or confirmatory testing This study investigated the prevalence of anti‐HTLV‐1 and HTLV‐2 antibodies in stored sera from a previous childhood cancer study. We had access to the sera of 534 children diagnosed with cancer in Blantyre, Malawi and 418 paired healthy mothers. ELISA positive tests were confirmed and typed by immunoblotting. In addition, we applied context to our results by conducting a systematic review and meta‐analysis of published HTLV seroprevalence data of African women and children.n = 534) and, where available, from their biological mothers (n = 418), were tested. Samples had been originally collected as part of a childhood malignancy and blood‐borne virus (BBV) study at the Queen Elizabeth Central Hospital in Blantyre, Malawi between 2006 and 2010 n = 174, maximum n = 276) or mothers , and data were not available for all data points. Results are, therefore, presented as % of data available.Anonymised stored serum samples from Malawian children (n = 18). DNA was isolated from frozen whole blood of serologically indeterminate samples and its integrity was confirmed by optimised PCR amplification of glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) using commercially available primers. Samples were tested for the presence of HTLV‐1 DNA by PCR as previously described Replicating clinical diagnostic algorithms, the study protocol required that all ELISA reactive samples underwent immunoblot (IB) confirmatory testing. Only indeterminate IBs were tested further with polymerase chain reaction (PCR), where whole blood was available. All sera were screened in duplicate by ELISA  following the manufacturers' instructions . ELISA reactive or borderline reactive sera were tested and typed as HTLV‐1, HTLV‐2, HTLV‐1 and HTLV‐2, negative and indeterminate using an FDA approved, confirmatory, qualitative enzyme immunoblot assay (IB), (MP Diagnostics HTLV blot v2.4), which were interpreted using the HTLV European Research Network guidelines PRISMA guidelines for systematic reviews and meta‐analyses were adhered to during protocol design and analyses. The NCBI PubMed database was searched using the search terms ‘HTLV’, ‘human T‐lymphotropic virus’, ‘mother’, ‘child’, ‘transmission’ plus each respective African nation to 31 December 2014.The inclusion criteria were cross‐sectional seroprevalence studies; healthy women ; sex workers; children; living in Africa; opt‐in, opt‐out or anonymous un‐linked (blood tests/other body fluid); approved by ethics; screened for HTLV; and confirmed with a confirmatory test (CT), and studies with zero seroprevalence by ELISA were included Figure . The excApplying the above criteria at stage 1 all potential papers' titles and abstracts were screened, and at stage 2 duplicates and papers not fitting all criteria were removed  and seven HTLV‐2 (1.7%) with one (0.2%) mother being dually infected , had been born vaginally, had not been born prematurely, had been breastfed for >2 years. Only one child had received injections in the past but none had had a blood transfusion and only three had a history of malaria.At stage 1, 766 PubMed publications on HTLV in African countries were identified. At stage 2, all publications that met the outlined inclusion/exclusion criteria were collected. Specific effort was made to extract data on women and children only from the manuscripts. Data were available for 24 countries for women and eight for children and were published between 1988 and 2014 for women and between 1988 and 1999 for children. Thirty‐four studies had data for cohorts of healthy volunteers, three for blood donors, twenty‐two for antenatal care (ANC) attendees and fifteen for sex workers. Mean sample size for women was 609 (range 26–2070) and 562 for children (range 46–1323). Some manuscripts gave data on multiple subgroups of study population therefore additional data sets were created. In the first instance, analysis was conducted on 74 data sets for women  but deliberately refrained from calculating a prevalence estimate for the African continent Table . For womP = 0.3). Therefore, although they had a slightly higher risk of being positive for HTLV, this may have been due to chance variation; therefore, sex workers were not excluded from the analysis.Assuming that sex workers may have an unusually high exposure risk we compared them to other women using logistic regression with robust standard errors allowing for the clustering in studies and adjusting for region. The odds ratio of HTLV for sex workers compared to all other women was 1.34 , Nigeria 1.1% and 3.9%  To our knowledge, this is the first report on the seroprevalence and type of HTLV in Malawi combining screening with robust confirmatory testing. We had access to stored sera of children with childhood cancers and their mothers as their controls who had taken part in a previous study In this retrospective study, the mothers were of child‐bearing age with known multiple pregnancies but we can only make assumptions about their HTLV acquisition. They could have acquired these viruses through: MTCT from their own mothers; unprotected sex; contact with non‐human primates , use of unsterile instrumentation  or contaminated needles; unscreened blood products or other means not yet characterised. Bush‐meat hunting, heroin trafficking and FGM are prevalent in Malawi although not sufficiently surveyed The lack of concordance between mothers and their children remains unexplained; it might be an indication of horizontal transmission or the possibility that the child had been breastfed by someone other than their mother. The origin and route of transmission of the unusually high HTLV‐2 seroprevalence found in our study participants remains unknown and prospective study would allow verification and identification of infection source.n = 740); this region seems to have a low HTLV seroprevalence, although this should be verified with additional larger prevalence studies.Our systematic review of HTLV in women and children confirmed a distribution of HTLV in large areas of Africa . HTLV was not detected in healthy women in the three eligible studies from North Africa (et al., it is possible that HTLV‐2 was present in these blood donors.The prevalence of HTLV‐1 in many areas of the world is poorly mapped and incidence of other subtypes is even less well known. Africa is thought to be endemic for HTLV In our systematic review only two other African countries reported high rates of HTLV‐2 seroprevalence: Nigeria and Eritrea, about 2000 miles apart. HTLV‐2 was not detected in Mozambique or Zambia, neighbouring countries of Malawi (Table et al., identified an HTLV‐1 infected child, from a total of 916 children screened, whose mother had an indeterminate serological pattern and a negative HTLV PCR result et al., reported five HTLV‐1‐positive children of 476 children from a total of 460 mothers in their study; none of the mothers of the infected children had HTLV Three manuscripts in our systematic review addressed HTLV MTCT The strengths of this study were the large total and matched sample sizes, the combination of highly sensitive and specific screening and confirmation testing and the HTLV mapping of Malawi, an under surveyed country. The study has several limitations. We tested stored samples and, therefore, were unable to prospectively collect demographic and risk factor data specific to HTLV seroprevalence studies. None of the HTLV‐positive cases were HIV positive, which is interesting in itself considering that both share the same route of transmission. Samples were also a few years old which might have affected their reactivity. The cohort of children had cancer and antibody cross reactivity might have led to false positive results, although the highly specific confirmatory testing should negate this risk and HTLV infections were also found in the healthy women. Additional molecular testing of seropositive samples would have been ideal but we did not have access to the required DNA.In our systematic review, we included data only on healthy women to best match our cohort of women and reduce co‐infection/co‐morbidity bias. There were very few published reports of childhood HTLV and we excluded those who were known HIV positive. We believe data from the 1980s are valuable, although an overestimation of HTLV prevalence is possible. Furthermore, because African HTLV seroprevalence studies are limited in their number, we did not exclude any samples based on study size but calculated regional estimates rather than national estimates in an attempt to reduce dependence upon studies with small cohorts. Inherent bias from small studies and those from the 1980s was reduced by including only publications that had used serological confirmatory testing. We used appropriate study weighting based on cohort size in our analyses and regional seroprevalence estimates.In summary, our study highlights that HTLV is prevalent in Malawi. However, neither ATLL nor HAM/TSP has been reported so far. These HTLV‐1‐associated diseases are difficult to diagnose with high risk of mortality from ATLL before diagnosis has been made. They are, therefore, notoriously underreported unless specifically looked for. In addition, HTLV‐2 is not as pathogenic as HTLV‐1 and will be transmitted unknowingly from generation to generation.Prospective field studies of HTLV as well as its associated diseases are needed in Malawi to allow health policy makers to develop practical and sustainable health policies with the long‐term aim of eradicating HLTV.