[Show abstract][Hide abstract] ABSTRACT: Objective:
To test the hypothesis that individuals who are active but who decrease physical activity (PA) over time have a higher risk of becoming obese in young adulthood, when compared to individuals who are consistently active throughout childhood and adolescence.
Iowa Bone Development Study cohort members (242 males and 251 females) participated in accelerometry assessments, dual-energy X-ray absorptiometry scans, and dietary questionnaire surveys at ages 5, 8, 11, 13, 15, 17, and 19 years. Group-based trajectory analyses identified distinct trajectory patterns of moderate- to vigorous-intensity PA (MVPA), percentage of body fat, and energy intake. A multivariable logistic regression model was fit to estimate the odds of "becoming obese" based on the MVPA trajectories, adjusted for mother's education, somatic maturation, and energy intake.
Among males, 74.7% had a "normal" body fat pattern, 14.6% had a "becoming obese" pattern, and 10.7% had a "consistently obese" pattern, while among females, the percentages were 58.6%, 28.6%, and 12.8%, respectively. Participants who were active (≥45 min MVPA) as children but decreased MVPA with age were more likely to become obese, compared to consistently active participants (adjusted OR = 2.77; 95% CI = 1.16, 6.58).
An active lifestyle throughout childhood and adolescence could prevent obesity development in young adulthood.
[Show abstract][Hide abstract] ABSTRACT: The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production.
No preview · Article · Oct 2015 · Translational Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Osteoporosis is a common bone disease associated with increased risk of low-trauma fractures leading to substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that trabecular bone (TB) microarchitectural quality is an important determinant of bone strength and fracture risk. A tensor scale based algorithm for in vivo characterization of TB plate-rod microarchitecture at the distal tibia using multirow detector CT (MD-CT) imaging is presented and its performance and applications are examined.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Cortical bone supports and protects human skeletal functions and plays an important role in determining bone strength and fracture risk. Cortical bone segmentation at a peripheral site using multirow-detector CT (MD-CT) imaging is useful for in vivo assessment of bone strength and fracture risk. Major challenges for the task emerge from limited spatial resolution, low signal-to-noise ratio, presence of cortical pores, and structural complexity over the transition between trabecular and cortical bones. An automated algorithm for cortical bone segmentation at the distal tibia from in vivo MD-CT imaging is presented and its performance and application are examined.
[Show abstract][Hide abstract] ABSTRACT: The diverse developmental patterns of obesogenic behaviors during childhood and adolescence can be better understood by using new analytic approaches to assess the heterogeneity in variation during growth and development and to map the clustering of behavior patterns.
To identify distinct trajectories of daily time spent in moderate- to vigorous-intensity physical activity (MVPA) from ages 5 to 19 years and to examine the associations of MVPA trajectories with sports participation and television viewing trajectories.
Cohort members in the prospective population-based Iowa Bone Development Study participated in MVPA assessments via accelerometry from September 16, 1998, to December 9, 2013, at ages 5, 8, 11, 13, 15, 17, and 19 years and completed a questionnaire every 6 months on sports participation and daily time spent in television viewing.
Trajectories of MVPA (minutes per day), participation in organized sports (yes or no), and television viewing time (hours per day).
Based on the data from 537 participants (50.1% females; 94.6% white), we identified 4 MVPA trajectories: consistently inactive (14.9%), consistently active (18.1%), decreasing moderate physical activity (52.9%), and substantially decreasing high physical activity (14.1%). All participants in the consistently inactive trajectory also followed a trajectory of no participation in sports. The consistently active trajectory was associated with decreasing an already low television viewing trajectory (P < .001).
This study provided a nuanced look at the known decrease in MVPA during childhood and adolescence. Sports participation could be a critical way to avoid the consistently inactive pattern. Most important, we identified a subset of participants who maintained a seemingly healthy level of MVPA from childhood to young adulthood. The developmental pathways of physical activity and television viewing behaviors could be related. Additional studies should examine the determinants and health consequences of these specific MVPA trajectories.
[Show abstract][Hide abstract] ABSTRACT: To assess association between lower body muscle power and bone strength, as well as the mediating effect of muscle cross-sectional area (MCSA) on that association.
Participants (N=141 males; 162 females) were approximately 17 years. Muscle power was predicted using vertical jump and the Sayers equation. Using peripheral quantitative computed tomography (pQCT), bone strength indices were obtained at two locations of the tibia, corresponding to primary stressors acting upon each site: bone strength index for compression (BSI) at the distal 4% site; density-weighted polar section modulus strength-strain index [SSIp] and cortical bone area (CoA) at the 66% mid-shaft site for torsion. Muscle cross-sectional area (MCSA) was measured at the 66% site. Pearson bivariate and partial correlation coefficients were estimated to quantify the strength of the associations among variables. Direct and indirect mediation model effects were estimated and 95% bootstrap confidence intervals were constructed to test the causal hypothesis. Height and maturity were examined as covariates.
Pearson correlation coefficients among muscle power, MCSA, and bone strength were statistically significant (p<0.01) and ranged from r=0.54 to 0.78. After adjustment for covariates, associations were reduced (r=0.37 to 0.69) (p<0.01). Mediation models for males for BSI, SSIp, and CoA accounted for 38%, 66%, and 54% of the variance in bone strength, respectively. Models for females for BSI, SSIp, and CoA accounted for 46%, 77%, and 66% of the variance, respectively.
We found strong and consistent associations, as well as direct and indirect pathways, among muscle power, MCSA, and tibia strength. These results support the use of muscle power as a component of health-related fitness in bone health interventions for older adolescents.
Full-text · Article · Feb 2015 · Medicine & Science in Sports & Exercise
[Show abstract][Hide abstract] ABSTRACT: Aging is a natural process involving complex interplay between environment, metabolism, and genes. Sirtuin genes and their downstream targets have been associated with lifespan in numerous organisms from nematodes to humans. Several target proteins of the sirtuin genes are key sensors and/or effectors of oxidative stress pathways including FOXO3, SOD3, and AKT1. To examine the relationship between single nucleotide polymorphisms (SNP) at candidate genes in these pathways and human lifespan, we performed a molecular epidemiologic study of an elderly cohort (≥65 years old.). Using age at death as a continuous outcome variable and assuming a co-dominant genetic model within the framework of multi-variable linear regression analysis, the genotype-specific adjusted mean age at death was estimated for individual SNP genotypes while controlling for age-related risk factors including smoking, body mass index, alcohol consumption and co-morbidity. Significant associations were detected between human lifespan and SNPs in genes SIRT3, SIRT5, SIRT6, FOXO3 and SOD3. Individuals with either the CC or CT genotype at rs107251 within SIRT6 displayed >5-year mean survival advantages compared to the TT genotype (5.5 and 5.9 years, respectively; q-value = 0.012). Other SNPs revealed genotype-specific mean survival advantages ranging from 0.5 to 1.6 years. Gender also modified the effect of SNPs in SIRT3, SIRT5 and AKT1 on lifespan. Our novel findings highlight the impact of sirtuins and sirtuin-related genotypes on lifespan, the importance of evaluating gender and the advantage of using age as a continuous variable in analyses to report mean age at death.
[Show abstract][Hide abstract] ABSTRACT: Background:
Adverse associations between maternal pesticide exposure and neural tube defects (NTDs) have been suggested but not consistently observed. This study used data from the multisite National Birth Defects Prevention Study to examine associations between maternal periconceptional (1 month preconception through 2 months postconception) occupational pesticide exposure and NTDs.
Mothers of 502 NTD cases and 2950 unaffected live-born control infants with estimated delivery dates from 1997 through 2002 were included. Duration, categorical intensity scores, and categorical frequency scores for pesticide classes (e.g., insecticides) were assigned using a modified, literature-based job-exposure matrix and maternal-reported occupational histories. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated based on fitted multivariable logistic regression models that described associations between maternal periconceptional occupational pesticide exposure and NTDs. The aORs were estimated for pesticide exposure (any [yes/no] and cumulative exposure [intensity × frequency × duration] to any pesticide class, each pesticide class, or combination of pesticide classes) and all NTD cases combined and NTD subtypes.
Positive, but marginally significant or nonsignificant, aORs were observed for exposure to insecticides + herbicides for all NTD cases combined and for spina bifida alone. Similarly, positive aORs were observed for any exposure and cumulative exposure to insecticides + herbicides + fungicides and anencephaly alone and encephalocele alone. All other aORs were near unity.
Pesticide exposure associations varied by NTD subtype and pesticide class. Several aORs were increased, but not significantly. Future work should continue to examine associations between pesticide classes and NTD subtypes using a detailed occupational pesticide exposure assessment and examine pesticide exposures outside the workplace.
No preview · Article · Nov 2014 · Birth Defects Research Part A Clinical and Molecular Teratology
[Show abstract][Hide abstract] ABSTRACT: Purpose: Greater visceral fat (VF) has been associated with with lower bone measures in youth, though this relationship has not been evaluated longitudinally. The purpose of this study was to determine if VF is negatively associated with bone parameters in overweight and obese adolescents from age 11-17.
Methods: Iowa Bone Development Study participants underwent peripheral quantitative computed tomography (pQCT) scans of the radius and tibia and whole body dual energy x-ray absorptiometry (DXA) scans every 2 years from age 11-17. Eligible participants were overweight or obese at age 11 according to CDC BMI percentiles and had age 11 baseline scans and age 15 or 17 follow-up. VF area (cm2) was estimated from whole body DXA scans using Apex 4.0 software (Hologic, Inc). Gender specific analyses evaluated the relationship between VF and bone development with growth models using biological age (visit age – age of peak height velocity) as the time variable adjusted for limb length and lean mass. Results are presented as standardized parameter estimates.
Results: Eligible participants included 42 girls(45% obese) and 52 boys (35% obese) with a mean age at baseline of 11.2±0.3 years. In girls, greater VF was associated with thinner cortical bone and lower strength-strain index (SSI) at the radius (20% site), but not tibia (Table). In boys, greater VF was associated with lower density and strength at the predominantly trabecular bone site (4%) at the tibia but not radius. At the cortical site in boys (20%), greater VF was associated with thinner bones at the radius with no significant associations at the tibia. In sensitivity analyses restricted to obese participants, results remained relatively unchanged in girls. In boys, the relationship between VF and SSI (20% site) became significant (-0.12±0.05, p=0.0260) while parameter estimates for associations at the 4% tibial site were attenuated and no longer reached significance (BMD: -0.14±0.08, p=0.11; BSI: -0.17±0.09, p=0.07).
Conclusions: Greater VF is associated with lower cortical bone strength at the non-weight-bearing radius but not at the tibia where greater mechanical loading may attenuate the negative relationship. Lower trabecular bone strength at the tibia with greater VF in boys may be a reflection of more rapid growth at that site. These results suggest the bone-fat relationship may vary depending on adiposity and bone site and explain previous, conflicting reports on this relationship.
[Show abstract][Hide abstract] ABSTRACT: This study examined the association between physical activity (PA) and bone mineral content (BMC; gram) from middle childhood to middle adolescence and compared the impact of vigorous-intensity PA (VPA) over moderate- to vigorous-intensity PA (MVPA). Participants from the Iowa bone development study were examined at ages 5, 8, 11, 13, and 15 years (n = 369, 449, 452, 410, and 307, respectively). MVPA and VPA (minutes per day) were measured using ActiGraph accelerometers. Anthropometry was used to measure body size and somatic maturity. Spine BMC and hip BMC were measured via dual-energy x-ray absorptiometry. Sex-specific multi-level linear models were fit for spine BMC and hip BMC, adjusted for weight (kilogram), height (centimeter), linear age (year), non-linear age (year(2)), and maturity (pre peak height velocity vs. at/post peak height velocity). The interaction effects of PA × maturity and PA × age were tested. We also examined differences in spine BMC and hip BMC between the least (10th percentile) and most (90th percentile) active participants at each examination period. Results indicated that PA added to prediction of BMC throughout the 10-year follow-up, except MVPA, did not predict spine BMC in females. Maturity and age neither modify the PA effect for males nor females. At age 5, the males at the 90th percentile for VPA had 8.5% more hip BMC than males in the 10th percentile for VPA. At age 15, this difference was 2.0%. Females at age 5 in the 90th percentile for VPA had 6.1% more hip BMC than those in the 10th percentile for VPA. The age 15 difference was 1.8%. VPA was associated with BMC at weight-bearing skeletal sites from childhood to adolescence, and the effect was not modified by maturity or age. Our findings indicate the importance of early and sustained interventions that focus on VPA. Approaches focused on MVPA may be inadequate for optimal bone health, particularly for females.
Full-text · Article · Jul 2014 · Frontiers in Endocrinology
[Show abstract][Hide abstract] ABSTRACT: Background:
Correction for soft tissue signal attenuation can improve the diagnostic accuracy of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). The aim of this study was to correlate SPECT-MPI findings with clinical outcomes in patients who underwent stress imaging in the supine position, who also underwent "second look" stress imaging in the prone position.
Patients without perfusion abnormalities were considered Normal (N = 270). Those with apparent supine stress perfusion abnormalities which all resolved during prone imaging formed the Normal-Prone group (N = 309). Patients with matched perfusion abnormalities during both supine and prone stress imaging were considered Abnormal (N = 169).
During follow-up (187 ± 96 days), utilization rates for invasive coronary angiography were similar for Normal vs Normal-Prone patients (3.5% vs 3.8%; P = NS), but were significantly higher in Abnormal patients (42.4%, P < .0001). Coronary revascularization occurred in 0.78%, 0.64%, and 17.7% of Normal, Normal-Prone, and Abnormal patients, respectively (P < .001). Cardiac death or myocardial infarction occurred in 2.2%, 2.3%, and 6.3% of Normal, Normal-Prone, and Abnormal patients, respectively (P = .02).
Second look SPECT-MPI identifies patients at low risk for death or myocardial infarction, who infrequently require invasive coronary angiography.
No preview · Article · Jul 2014 · Journal of Nuclear Cardiology
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Substantial evidence exists to indicate bidirectional relationships between obesity and depressive disorders and the importance of fat distribution to this relationship. This analysis used a well-characterized sample of individuals in late adolescence to determine the association between depressive illness and fat distribution.
In adolescents, relationships between central adiposity and major depressive disorder (MDD) may be confined to those who are overweight/obese. Despite the high co-morbidity of anxiety and depressive disorders, only the latter appeared to be significantly associated with adiposity.
[Show abstract][Hide abstract] ABSTRACT: Background Physical activity improves bone strength and reduces the risk for osteoporotic fractures. However, there are substantial gaps in our knowledge as to when, how and how much activity is optimal for bone health.
Purpose In this cohort study, we examined developmental trajectories of objectively measured physical activity from childhood to adolescence to discern if moderate-and-vigorous intensity physical activity (MVPA) predicts bone strength.
Methods Starting at age 5 and continuing at 8, 11, 13, 15 and 17 years, Iowa Bone Development Study participants (n=530) wore an accelerometer for 3–5 days. At age 17, we assessed dual X-ray energy absorptiometry outcomes of mass and estimated geometry (femoral neck cross-sectional area and section modulus). We also assessed geometric properties (bone stress index and polar moment of inertia) of the tibia using peripheral computer quantitative tomography. Latent class modelling was used to construct developmental trajectories of MVPA from childhood to late adolescence. General linear models were used to examine the trajectory groups as predictors of age 17 bone outcomes.
Results Girls and boys who accumulated the most MVPA had greater bone mass and better geometry at 17 years when compared to less active peers. The proportion of participants achieving high levels of MVPA throughout childhood was very low (<6% in girls) and by late adolescence almost all girls were inactive.
Conclusions Bone health benefits of physical activity are not being realised due to low levels of activity for most youth, especially in girls.
Full-text · Article · May 2014 · British Journal of Sports Medicine
[Show abstract][Hide abstract] ABSTRACT: Objective
To examine associations among age, physical activity (PA), and birth cohort on body mass index (BMI) percentiles in men.
Design and Methods
Longitudinal analyses using quantile regression were conducted among men with ≥ two examinations between 1970 and 2006 from the Aerobics Center Longitudinal Study (n=17,759). Height and weight were measured; men reported their PA and were categorized as inactive, moderately or highly active at each visit. Analyses allowed for longitudinal changes in PA.
BMI was greater in older than younger men and in those born in 1960 than those born in 1940. Inactive men gained weight significantly more rapidly than active men. At the 10th percentile, increases in BMI among inactive, moderately active, and highly active men were 0.092, 0.078, and 0.069 kg/m2 per year of age, respectively. The 10th percentile increased by 0.081 kg/m2 per birth year and by 0.180 kg/m2 at the 90th percentile, controlling for age.
Although BMI increased with age, PA reduced the magnitude of the gradient among active compared to inactive men. Regular PA had an important, protective effect against weight gain. This study provides evidence of the utility of quantile regression to examine the specific causes of the obesity epidemic.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Second-generation antipsychotics (SGAs) cause weight gain and cardiometabolic abnormalities in children and adolescents. Less well-investigated is the outcome of these adverse events following SGA discontinuation, which we examined.
Medically healthy 7 to 17-year-old patients treated with risperidone for ≥6 months were enrolled and returned for follow-up, 1.5 years later. Treatment history was extracted from the medical and pharmacy records. Anthropometric and laboratory measurements were obtained at each research visit. Multivariable linear regression analysis and Fisher's exact test were used to compare participants who remained on risperidone at follow-up (Risp Cont Group) with those who had discontinued SGA treatment (SGA Disc Group) and those who had switched to another SGA (SGA Cont Group). Correlational analyses examined the association between change in age-sex specific body mass index (BMI) z score between study entry and follow-up and change in cardiometabolic outcomes.
The sample consisted of 101 participants (93% male) with a mean age of 11.7±2.6 years at study entry. The majority had an externalizing disorder and received 0.03±0.02 mg/kg/day of risperidone, for 2.5±1.6 years. At follow-up, 18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group. BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI z score between study entry and follow-up was significantly correlated with the change in systolic and diastolic blood pressure z scores, heart rate, waist circumference, percent body fat, inflammatory markers, fasting total insulin, homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, triglycerides, triglycerides/HDL ratio, and leptin.
Following several years of treatment, risperidone discontinuation is associated with a reversal of the excessive weight gain, mediated by a negative energy balance, and a corresponding improvement in cardiometabolic parameters.
Preview · Article · Apr 2014 · Journal of child and adolescent psychopharmacology
[Show abstract][Hide abstract] ABSTRACT: Choanal atresia causes serious posterior nasal obstruction. This defect is the leading cause of nasal surgery in newborns, although its etiology is largely unknown. Data from the National Birth Defects Prevention Study, a population-based case-control study, were used to examine associations between maternal self-reports of exposures and occurrence of choanal atresia in their offspring. Overall, 117 case and 8350 control mothers with deliveries from 1997-2007 provided telephone interview reports of pre-pregnancy (one year before conception) and periconceptional (one month before through three months after conception) exposures. Exposures analyzed were pre-pregnancy dietary intake, pre-pregnancy and periconceptional caffeine consumption, and periconceptional cigarette smoking, alcohol drinking, and medication use. Independent associations between each exposure and all choanal atresia cases combined (n=117) and isolated choanal atresia cases (those without additional unrelated major defects; n=61) were examined. Odds ratios (ORs), both unadjusted (uORs) and adjusted (aORs) for potential confounders, and 95% confidence intervals (CI)s were estimated using unconditional logistic regression analysis. For all choanal atresia cases combined, positive associations were observed with maternal pre-pregnancy intake in the highest quartile for vitamin B-12 (aOR=1.9; CI=1.1,3.1), zinc (aOR=1.7; CI=1.0,3.1), and niacin (aOR=1.8; CI=1.0,3.1), and intake in the lowest quartile for methionine (aOR=1.6; CI=1.0,2.6) and vitamin D (aOR=1.6; CI=1.0,2.4) compared to intake in the two intermediate quartiles combined. Further, a positive association was observed with periconceptional use of thyroid medications (uOR=2.6; CI=1.0,6.3) compared to no use of such medications. Among isolated choanal atresia cases, negative associations were observed for pantothenic acid (aOR=0.4; CI=0.2,0.9) and fat (aOR=0.5; 95% CI=0.2,1.0) intake in the lowest quartile compared to that in the intermediate quartiles, and positive associations were observed for periconceptional cigarette smoking (aOR=2.3; CI=1.1,4.7) compared to no smoking and pre-pregnancy daily coffee intake of 3 or more cups (aOR=2.5; CI=1.1,5.6) compared to intake of less than 1 cup per day. The positive association for periconceptional exposure to thyroid medications also persisted for isolated choanal atresia cases (uOR=4.0; CI=1.1,11.2). Because of the large number of associations tested, these findings may be due to chance. Alternatively, they may contribute new hypotheses regarding the etiology of choanal atresia; thus, requiring replication in additional studies.
No preview · Article · Apr 2014 · European journal of medical genetics
[Show abstract][Hide abstract] ABSTRACT: Adult bone diseases, especially osteoporosis, lead to increased risk of fracture which in turn is associated with substantial morbidity, mortality, and financial costs. Clinically, osteoporosis is defined by low bone mineral density (BMD); however, increasing evidence suggests that the micro-architectural quality of trabecular bone (TB) is an important determinant of bone strength and fracture risk. Accurate measures of TB thickness and marrow spacing is of significant interest for early diagnosis of osteoporosis or treatment effects. Here, we present a new robust algorithm for computing TB thickness and marrow spacing at a low resolution achievable in vivo. The method uses a star-line tracing technique that effectively deals with partial voluming effects of in vivo imaging with voxel size comparable to TB thickness. Also, the method avoids the problem of digitization associated with conventional algorithms based on sampling distance transform along skeletons. Accuracy of the method was examined using computer-generated phantom images while the robustness of the method was evaluated on human ankle specimens in terms of stability across a wide range of voxel sizes, repeat scan reproducibility under in vivo conditions, and correlation between thickness values computed at ex vivo and in vivo imaging resolutions. Also, the sensitivity of the method was examined by evaluating its ability to predict the bone strength of cadaveric specimens. Finally, the method was evaluated in a human study involving 40 healthy young-adult volunteers (age: 19 to 21 years; 20 males and 20 females) and ten athletes (age: 19 to 21 years; 6 males and 4 females). Across a wide range of voxel sizes, the new method is significantly more accurate and robust as compared to conventional methods. Both TB thickness and marrow spacing measures computed using the new method demonstrated strong associations (R2 2 [0:83; 0:87]) with bone strength. Also, the TB thickness and marrow spacing measures allowed discrimination between male and female volunteers (p 2 [0:01; 0:04]) as well as between athletes and non-athletes (p 2 [0:005; 0:03]).
Full-text · Article · Mar 2014 · IEEE transactions on bio-medical engineering