Risk prediction of complex diseases from family history and known susceptibility loci, with applications for cancer screening

Risk prediction based on genomic profiles has raised a lot of attention recently. However, family history is usually ignored in genetic risk prediction. In this study we proposed a statistical framework for risk prediction given an individual's genotype profile and family history. Genotype information about the relatives can also be incorporated. We allow risk prediction given the current age and follow-up period and consider competing risks of mortality. The framework allows easy extension to any family size and structure. In addition, the predicted risk at any percentile and the risk distribution graphs can be computed analytically. We applied the method to risk prediction for breast and prostate cancers by using known susceptibility loci from genome-wide association studies. For breast cancer, in the population the 10-year risk at age 50 ranged from 1.1% at the 5th percentile to 4.7% at the 95th percentile. If we consider the average 10-year risk at age 50 (2.39%) as the threshold for screening, the screening age ranged from 62 at the 20th percentile to 38 at the 95th percentile (and some never reach the threshold). For women with one affected first-degree relative, the 10-year risks ranged from 2.6% (at the 5th percentile) to 8.1% (at the 95th percentile). For prostate cancer, the corresponding 10-year risks at age 60 varied from 1.8% to 14.9% in the population and from 4.2% to 23.2% in those with an affected first-degree relative. We suggest that for some diseases genetic testing that incorporates family history can stratify people into diverse risk categories and might be useful in targeted prevention and screening.     

Longitudinal study of body weight changes in children: who is gaining and who is losing weight

Cross-sectional studies have reported significant temporal increases in prevalence of childhood obesity in both genders and various racial groups, but recently the rise has subsided. Childhood obesity prevention trials suggest that, on average, overweight/obese children lose body weight and nonoverweight children gain weight. This investigation tested the hypothesis that overweight children lose body weight/fat and nonoverweight children gain body weight/fat using a longitudinal research design that did not include an obesity prevention program. The participants were 451 children in 4th to 6th grades at baseline. Height, weight, and body fat were measured at month 0 and month 28. Each child's BMI percentile score was calculated specific for their age, gender and height. Higher BMI percentile scores and percent body fat at baseline were associated with larger decreases in BMI and percent body fat after 28 months. The BMI percentile mean for African-American girls increased whereas BMI percentile means for white boys and girls and African-American boys were stable over the 28-month study period. Estimates of obesity and overweight prevalence were stable because incidence and remission were similar. These findings support the hypothesis that overweight children tend to lose body weight and nonoverweight children tend to gain body weight.     

Dose coefficients of percentile-specific computational phantoms for photon external exposures

The use of dose coefficients (DCs) based on the reference phantoms recommended by the International Commission on Radiological Protection (ICRP) with a fixed body size may produce errors to the estimated organ/tissue doses to be used, for example, for epidemiologic studies depending on the body size of cohort members. A set of percentile-specific computational phantoms that represent 10th, 50th, and 90th percentile standing heights and body masses in adult male and female Caucasian populations were recently developed by modifying the mesh-type ICRP reference computational phantoms (MRCPs). In the present study, these percentile-specific phantoms were used to calculate a comprehensive dataset of body-size-dependent DCs for photon external exposures by performing Monte Carlo dose calculations with the Geant4 code. The dataset includes the DCs of absorbed doses for 29 individual organs/tissues from 0.01 to 104 MeV photon energy, in the antero-posterior, postero-anterior, right lateral, left lateral, rotational, and isotropic geometries. The body-size-dependent DCs were compared with the DCs of the MRCPs in the reference body size, showing that the DCs of the MRCPs are generally similar to those of the 50th percentile standing height and body mass phantoms over the entire photon energy region except for low energies (≤ 0.03 MeV); the differences are mostly less than 10%. In contrast, there are significant differences in the DCs between the MRCPs and the 10th and 90th percentile standing height and body mass phantoms (i.e., H10M10 and H90M90). At energies of less than about 10 MeV, the MRCPs tended to under- and over-estimate the organ/tissue doses of the H10M10 and H90M90 phantoms, respectively. This tendency was revised at higher energies. The DCs of the percentile-specific phantoms were also compared with the previously published values of another phantom sets with similar body sizes, showing significant differences particularly at energies below about 0.1 MeV, which is mainly due to the different locations and depths of organs/tissues between the different phantom libraries. The DCs established in the present study should be useful to improve the dosimetric accuracy in the reconstructions of organ/tissue doses for individuals in risk assessment for epidemiologic investigations taking body sizes into account.     

Homeostatic model assessment (HOMA) index cut-off values to identify the metabolic syndrome in children

The aim of the study was to establish the best cut-off value for the homeostatic model assessment (HOMA) index in identifying children and adolescents with the metabolic syndrome. The study included 72 non-obese and 68 obese children aged 7 to 16 years. Obesity is defined using the criteria proposed by Cole et al., being included as metabolic syndrome variables waist circumference, systolic blood pressure, diastolic blood pressure and seric values of glucose, uric acid, fasting insulin, leptin, triglycerides and HDL-cholesterol. Children were considered as having the metabolic syndrome when four or more characteristics showed abnormal values. The HOMA index was calculated as the product of the fasting plasma insulin level (microU/mL) and the fasting plasma glucose level (mmol/L), divided by 22.5. HOMA index cut-offs from the 5th to the 95th percentile were used. A receiver operating characteristic (ROC) curve was generated using the different HOMA cut-offs for the screening of the metabolic syndrome. The areas under the ROC curve, 95% confidence intervals, and the point to the ROC curve closest to 1, were calculated. The area under the ROC curve was 0.863 (95% C.I.: 0.797, 0.930). The point closest to 1 corresponds to the 60th percentile of the HOMA index distribution in our sample. HOMA index value at the 60th percentile was 2.28. Cut-off values corresponding to a range of HOMA index from the 50 to the 75 percentile, showed similar distances to 1. HOMA index values for percentiles 50 to 75 ranged from 2.07 to 2.83. In conclusion, HOMA index could be a useful tool to detect children and adolescents with the metabolic syndrome. HOMA cut-off values need to be defined in the paediatric population; however, values near to 3 seem to be adequate.     

Periportal fibrosis in human Schistosoma mansoni infection is associated with low IL-10, low IFN-gamma, high TNF-alpha, or low RANTES, depending on age and gender

Schistosoma mansoni infection is highly endemic in parts of Uganda, and periportal fibrosis is common in communities along the shore of Lake Albert. In this study, we have identified cellular immune responses associated with fibrosis. A cohort of 199 individuals aged 6-50, resident in the village for at least 10 years or since birth, were examined for evidence of periportal fibrosis by ultrasound using the Niamey protocol. Whole-blood samples were assayed for levels of nine cellular immune molecules (IL-3, IL-4, IL-5, IL-10, IL-13, TNF-alpha, IFN-gamma, IL-1beta, and RANTES) in the absence of in vitro Ag stimulation, and after stimulation with egg and worm Ags. A lack of Ag specificity allowed the number of variables in the analysis to be reduced by factor analysis. The resulting factor scores were then entered into a risk analysis using a classification tree algorithm. Children, adult males, and adult females had different factors associated with fibrosis. Most cases of fibrosis in children (eight of nine) were associated with low (<47th percentile) IL-10 factor scores. Adult females at lowest risk had relatively high IFN-gamma factor scores (>83rd percentile), whereas those at highest risk had a combination of intermediate (32nd to 83rd percentile) IFN-gamma and relatively high (>60th percentile) TNF-alpha factor scores. Adult males at lowest risk of fibrosis had moderate TNF-alpha factor scores (55th to 82nd percentile), and a high risk was associated with either high TNF-alpha factor scores (>82nd percentile), or intermediate TNF-alpha combined with low RANTES factor scores (<58th percentile). These results demonstrate that periportal fibrosis is associated with cytokine production profiles that vary with both age and gender.     

Antiparasitic drugs for paediatrics: systematic review, formulations, pharmacokinetics, safety, efficacy and implications for control

Drug development for paediatric applications entails a number of challenges, such as the wide age spectrum covered - from birth to adolescence - and developmental changes in physiology during biological maturation that influence the efficacy and toxicity of drugs. Safe and efficacious antiparasitic drugs for children are of pivotal importance given the large proportion of burden attributable to parasitic diseases in this age group, and growing efforts to administer, as widely as possible, antiparasitic drugs to at-risk populations, such as infants and school-aged children, often without prior diagnosis. The purpose of this review is to investigate whether antiparasitic drugs have been adequately studied for use in paediatrics. We approached this issue through a systematic review using PubMed and the Cochrane Central Register of Trials covering a period of 10 years and 8 months until the end of August 2010 to identify trials that investigated efficacy, safety and pharmacokinetic (PK) parameters of antiparasitic drugs for paediatrics. Overall, 269 clinical drug trials and 17 PK studies met our inclusion criteria. Antimalarial drugs were the most commonly studied medicines (82·6%). Most trials were carried out in Africa and children aged 2-11 years were the age group most often investigated. Additionally, we critically examined available drug formulations for anthelminthics and identified a number of shortcomings that are discussed. Finally, we shed new light on current proposals to expand 'preventive chemotherapy' to preschool-aged children and emphasise that new research, including risk-benefit analyses, are needed before such a strategy can be adopted more widely.     

Racial Differences in the Tracking of Childhood BMI to Adulthood

Objective: The possibility that there are racial differences in the patterns of BMI (kilograms per meter squared) change throughout life has not been examined. For example, the high prevalence of obesity among black women could result from a higher prevalence of obesity among black girls or because normal‐weight black girls experience larger BMI increases in adolescence or adulthood than do their white counterparts. Therefore, we examined the tracking of childhood BMI into adulthood in a biracial (36% black) sample. Research Methods and Procedures: Five‐ to 14‐year‐old children (2392) were followed for (mean) 17 years. Childhood overweight was defined as BMI ≥ 95th percentile, and adult obesity was defined as BMI ≥ 30 kg/m². Results: The tracking of childhood BMI differed between whites and blacks. Among overweight children, 65% of white girls vs. 84% of black girls became obese adults, and predictive values among boys were 71% (whites) vs. 82% (blacks). These racial differences reflected contrasting patterns in the rate of BMI change. Although the initial BMI of black children was not higher than that of white children, BMI increases with age were larger among black girls and overweight black boys than among their white counterparts. In contrast, relatively thin (BMI < 50th percentile) white boys were more likely to become overweight adults than were their black counterparts. Discussion: These findings emphasize the black/white differences in BMI changes with age. Because of the adult health consequences of childhood‐onset obesity, early prevention should be given additional emphasis.     

Iron deficiency anemia and steady-state work performance at high altitude

Thirty-seven young adult male highland residents at 3,600-4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the FcRn developmental pharmacology on the pharmacokinetics of therapeutic monoclonal IgG antibody in pediatric subjects using minimal physiologically-based pharmacokinetic modelling

The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab and palivizumab) were used. The adult group contained six subjects with weights from 50 to 100 kg. For pediatric subjects, seven age groups were assumed, with five subjects each having the weight of 95%, 75%, 50%, 25% and 5% percentile of the population. A first evidence-based rating system to evaluate the quality of the source data used to derive pediatric-specific mPBPK model parameter was proposed. A stepwise approach was used to examine the best combination of age/weight effect on the parameters of the mPBPK model in adult and pediatric subjects. IgG synthesis rate (K_syn), extravasation rate (ER) and FcRn were fitted simultaneously to the PK of bevacizumab and native-IgG in both adult and pediatric. All fitting showed good fits based on the graphs and the coefficient of variation of the fitted parameters (< 50%). Estimated weight-normalized K_syn increased while weight-normalized FcRn and ER decreased with increasing age. The age and weight effect on FcRn were successfully estimated from the data. The final mPBPK model developed with native IgG and bevacizumab was able to predict the PK of palivizumab in pediatric subjects. Implementation of the mPBPK model enables us to analyze the relationships of age, weight, FcRn, ER and K_syn in both adult and pediatric subject. This information may benefit the understanding of complex interaction between the FcRn developmental pharmacology and PK parameters, and improve the prediction of the antibody disposition in pediatric subjects.     

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review

Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight‐based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.     

Quantitative risk assessment for multivariate continuous outcomes with application to neurotoxicology: the bivariate case

The neurotoxic effects of chemical agents are often investigated in controlled studies on rodents, with multiple binary and continuous endpoints routinely collected. One goal is to conduct quantitative risk assessment to determine safe dose levels. Such studies face two major challenges for continuous outcomes. First, characterizing risk and defining a benchmark dose are difficult. Usually associated with an adverse binary event, risk is clearly definable in quantal settings as presence or absence of an event; finding a similar probability scale for continuous outcomes is less clear. Often, an adverse event is defined for continuous outcomes as any value below a specified cutoff level in a distribution assumed normal or log normal. Second, while continuous outcomes are traditionally analyzed separately for such studies, recent literature advocates also using multiple outcomes to assess risk. We propose a method for modeling and quantitative risk assessment for bivariate continuous outcomes that address both difficulties by extending existing percentile regression methods. The model is likelihood based; it allows separate dose-response models for each outcome while accounting for the bivariate correlation and overall characterization of risk. The approach to estimation of a benchmark dose is analogous to that for quantal data without the need to specify arbitrary cutoff values. We illustrate our methods with data from a neurotoxicity study of triethyl tin exposure in rats.     

Ecology of Children’s Growth: An Example from Transitional Populations of the Brazilian Amazon

The intense environmental and social changes taking place in Amazonia make this a key area for health studies of populations transitioning to a cosmopolitan lifestyle and market economy. Caboclos are among those populations. They comprise the majority of rural Brazilian Amazon peoples. At present there is limited information about their patterns of growth and health. In this paper, anthropometric data on Caboclo children from three groups living in different environments are presented and discussed within a bioanthropological framework. Caxiuanã, Aracampina, and Santana have a combined population of 1,069 people. Caxiuanã relies more on subsistence activities for survival and Santana more on commerce, while Aracampina uses both subsistence strategies. Compared to US children, Caboclo are generally shorter and lighter in all age groups. However, their weight-for-height is above the 50th percentile. In relation to skinfolds, age groups 0–2, 6–8, and 9–11 years present statistically significant differences among the three communities. Caxiuanã children have the smallest and Aracampina children have the largest skinfolds. While seasonal and environmental differences may account for some of the observed variation in growth and fatness patterns, socioeconomic factors also play a key role in the trends observed. Thus, an ecological model provides the best framework for explaining these findings. Caxiuanã children are small and thin as a result of their combined poor environment and limited access to cash, western goods, and health care. Aracampina and Santana’s fuller access to such socioeconomic influences and richer ecology results in taller and fatter children. Understanding similar interactions between ecology and social factors will be fundamental to developing sustainable health initiatives among rural Amazonian populations.     

Long-term changes in body weight, BMI, and adiposity rebound among children and adolescents in the Czech republic

The Czech Republic has undergone rapid political, social, and economic transformation since the late 1980s. While obesity rates among children and adolescents in the Czech Republic have been previously relatively low, this has changed in recent years. Across the past 50 years, body weight, body mass index (BMI)-for-age, and adiposity rebound (AR) (the time when a child reaches the lowest BMI before their BMI gradually begins to increase until adulthood) occurs earlier. The most dramatic changes have been observed among school-aged children, where BMI values have increased at the 50th, 90th, and 97th percentiles. In contrast, adolescent girls appear to be thinner than in the past. The analyses of weight-for-height percentiles indicated that the 50th percentile of the body weight among boys and girls remained similar in nearly all age categories across the past 50 years. Although the growth pattern of children at the 50th percentile has not changed, the 10th and 90th percentiles have expanded. Our findings suggest that the secular trend of increased height, accelerated growth, and earlier maturation is responsible for Czech children experiencing adiposity rebound at earlier ages compared to the past.     

Parental perceptions of overweight counseling in primary care: the roles of race/ethnicity and parent overweight

Objective: To examine parental perceptions of primary care efforts aimed at childhood obesity prevention Methods and Procedures: We interviewed 446 parents of children, aged 2–12 years, with an age‐ and sex‐specific BMI ≥85th percentile; interviews occurred within 2 weeks of their child's primary care visit. We assessed parental ratings of the nutrition and physical activity advice received. Using children's clinical heights and weights and parents' self‐reported heights and weights, we classified children into three categories: BMI 85th–94th percentile without an overweight parent, BMI 85th–94th percentile with an overweight parent (adult BMI ≥25 kg/m²), and BMI ≥95th percentile. Results: In multivariate analyses, compared to parents of children with BMI ≥95th percentile, overweight parents with children whose BMI was 85th–94th percentile were more likely to report receiving too little advice on nutrition and physical activity (odds ratio (OR) 3.05; 95% confidence interval (CI) 1.49, 6.25) and to rate as poor or fair the quality of advice they received (OR 2.23; 95% CI 1.18, 4.24). Independently, African‐American (OR 2.55; 95% CI 1.18, 5.51) and Hispanic/Latino (OR 2.78; 95% CI 1.27, 6.10) parents were more likely than white parents to rate as poor or fair the quality of advice they received. Discussion: Parental overweight is associated with low subjective ratings of overweight counseling in pediatric primary care. Our findings of poorer perceived quality among racial/ethnic minority parents need further investigation.     

Investigation of the Locus Near MC4R With Childhood Obesity in Americans of European and African Ancestry

Recently a modest, but consistently, replicated association was demonstrated between obesity and the single‐nucleotide polymorphism (SNP), rs17782313, 3′ of the MC4R locus as a consequence of a meta‐analysis of genome‐wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European‐American (EA) obese children (BMI ≥95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African‐American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3′ to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs.     

Height and Adiposity among Children

Objectives : Although BMI (kilograms per meter squared) is widely used as a surrogate measure of adiposity, it is moderately associated (r ～ 0.3) with height among children. We examined whether the resulting preferential classification of taller children as overweight, based on a BMI ≥95th percentile, is appropriate. Research Methods and Procedures : We assessed the cross‐sectional relation of height among 5‐ to 18‐year‐old subjects (n = 1180) to levels of BMI, the sum of 10 skinfold thicknesses, and percentage body fat as determined by DXA. Results : The prevalence of a BMI level ≥95th percentile was substantially higher among 5‐ to 11‐year‐old subjects who were relatively tall for their age than among shorter children. Among 5‐ to 8‐year‐old boys, for example, each SD increase in height‐for‐age was associated with a 4.6‐fold increase in the prevalence of overweight (p < 0.001). Height not only was associated with BMI but also showed similar correlations with the skinfold sum and with percentage body fat; furthermore, the magnitudes of these associations decreased with age. We also found that the association between percentage body fat and BMI (r = 0.85 to 0.90) was close to the maximum correlation that can be achieved by any weight‐height index. Discussion : The use of BMI, which preferentially classifies taller young children as overweight, is appropriate because height and adiposity are correlated before the age of 12 years.     

Weight Loss Surgery Eligibility According to Various BMI Criteria Among Adolescents

A BMI cutoff point at the 99th percentile for age and gender or at 40 kg/m² has been suggested for more aggressive treatment of adolescent obesity. The main objective of this study was to determine the proportion of adolescents eligible for weight loss surgery (WLS) based on various BMI cutoff points. Data was extracted from the electronic medical record database of an urban pediatric ambulatory care center over 4 years. National data were used to calculate BMI percentiles (Centers for Disease Control and Prevention (CDC), 2000). Eligibility for WLS was based on a BMI percentile criterion (≥99th percentile) or the adult WLS cutoff point (≥40 kg/m²). The sample consisted of 3,220 adolescents aged 12–17.9 years, of which 53% were female, 55% were of black race, and 17% of Hispanic ethnicity. Overall, 88 (3%) adolescents had a BMI ≥40 kg/m² and 236 (7%) had a BMI ≥99th percentile (P < 0.001). All adolescents with BMI ≥40 kg/m² had a BMI ≥99th percentile. A total of 159/2,007 (8%) of 12–14.9‐year olds had a BMI ≥99th percentile compared with 77/1,213 (6%) 15–17.9‐year olds (P = 0.10), whereas 43/2,007 (2%) of 12–14.9‐year olds had a BMI ≥40 kg/m² compared with 45/1,213 (4%) 15–17.9‐year olds (P = 0.003). In summary, a relatively large proportion of adolescents from a diverse urban population would qualify for WLS based on the percentile criterion. Fewer adolescents would be eligible based on the adult WLS criterion, and younger adolescents would be less likely to be eligible for WLS than older adolescents.     

Severe Iron Deficiency Anemia

Severe iron deficiency anemia remains a continuing major health hazard among inner city children in Los Angeles. Over a 24-month period, 60 children in whom hemoglobin values were below 7 grams per dl were admitted to hospital; 11 (18 percent) of them were in overt congestive heart failure. Contrary to the popular conceptions, two thirds of the anemic children were undernourished, approximating the 16th percentile for weight on the Iowa growth chart, and the frequency of premature birth was not greater than in the general population. There were no deaths in this series. A management protocol which included partial exchange transfusion of children in congestive heart failure and supportive transfusion for children with hemoglobin levels below 5 grams per dl was employed.     

Wind and Water Dispersal of Wetland Plants Across Fragmented Landscapes

Biodiversity in wetlands is threatened by habitat loss and fragmentation, of which agricultural activities often are a cause. Dispersal of plant seeds via wind and ditches (water) may contribute to connecting remnant wetland plant populations in modern agricultural landscapes, and help to maintain and restore biodiversity. We developed a spatially explicit model to assess the relative importance of dispersal by wind and dispersal by water through drainage ditches for two wetland plant species in agricultural landscapes: a typical wind disperser and a typical water-disperser. Simulation results show that the typical wind disperser had a much higher capability to disperse by wind (90th percentile <30 m) than the typical water-disperser (90th percentile <2 m). Surprisingly, the capability to disperse via water was similar for the two species: 90th percentile dispersal distances following a combination of wind and water dispersal were between approximately 100 and 1000 m. Dispersal by water transported more seeds over long distances for both species. The main determinants for dispersal distance by water were roughness of the ditch (determined by, for example, bank vegetation) and the presence of obstructions (for example, culverts). Density or direction of the ditch network did not seem to affect water dispersal distances substantially. From a biodiversity conservation perspective, it would be most useful if areas with suitable riparian wetland habitat were intersected with a network of shallow ditches with a high roughness promoting seed deposition. These areas should then be connected to other suitable areas by a few regularly cleaned ditches with no obstructions and low seed trapping probability.