| 1. |
- Johnson, Randi K., et al.
(author)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Journal article (peer-reviewed)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 2. |
- Krischer, Jeffrey P, et al.
(author)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 3. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 4. |
- Abtahi, Farhad, 1981-
(author)
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Towards Heart Rate Variability Tools in P-Health : Pervasive, Preventive, Predictive and Personalized
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Heart rate variability (HRV) has received much attention lately. It has been shown that HRV can be used to monitor the autonomic nervous system and to detect autonomic dysfunction, especially vagal dysfunction. Reduced HRV is associated with several diseases and has also been suggested as a predictor of poor outcomes and sudden cardiac death. HRV is, however, not yet widely accepted as a clinical tool and is mostly used for research. Advances in neuroimmunity with an improved understanding of the link between the nervous and immune systems have opened a new potential arena for HRV applications. An example is when systemic inflammation and autoimmune disease are primarily caused by low vagal activity; it can be detected and prognosticated by reduced HRV. This thesis is the result of several technical development steps and exploratory research where HRV is applied as a prognostic diagnostic tool with preventive potential. The main objectives were 1) to develop an affordable tool for the effective analysis of HRV, 2) to study the correlation between HRV and pro-inflammatory markers and the potential degree of activity in the cholinergic anti-inflammatory pathway, and 3) to develop a biofeedback application intended for support of personal capability to increase the vagal activity as reflected in increased HRV. Written as a compilation thesis, the methodology and the results of each study are presented in each appended paper. In the thesis frame/summary chapter, a summary of each of the included papers is presented, grouped by topic and with their connections. The summary of the results shows that the developed tools may accurately register and properly analyse and potentially influence HRV through the designed biofeedback game. HRV can be used as a prognostic tool, not just in traditional healthcare with a focus on illness but also in wellness. By using these tools for the early detection of decreased HRV, prompt intervention may be possible, enabling the prevention of disease. Gamification and serious gaming is a potential platform to motivate people to follow a routine of exercise that might, through biofeedback, improve HRV and thereby health.
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| 5. |
- Chen, Hongjian, 1992-, et al.
(author)
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Polymer Microbubbles as Dual Modal Contrast Agent for Ultrasound and Computed Tomography
- 2018
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Conference paper (peer-reviewed)abstract
- The hybrid imaging combines the anatomical information with the functional or metabolic information using different conventional single imaging modalities improving the overall diagnosis outcome of the clinical examination. Since the introduction of the first hybrid imaging device PET-CT in 1998 different combinations of hybrid imaging were developed such as PET-MRI, SPECT-CT.However, lack of multimodal contrast agent specifically aimed for hybrid imaging limits the diagnostic outcome of these novel techniques. Initial attempts in fabrication of hybrid contrast agents were made by combining previously existing single modal contrast agents into one. In this study, polyvinyl alcohol (PVA) microbubbles (MB) and gold nanoparticles - which by themselves are already established contrast agents used in preclinical studies for ultrasound and CT, respectively - were chosen as parent contrast agents to fabricate the dual modal Contrast Agent for UltraSound and CT (CACTUS).MethodThe fabrication of MBs was adapted from Cavalieri et al.[1]. PVA powder (Sigma Aldrich, MO USA) was dissolved in the water at 80°C. The aqueous PVA-chains were cleaved by sodium metaperiodate (NaIO4, purity>99.0%, Sigma Aldrich, MO USA). Vigorous stirring force was applied to the resulting telechelic aldehydic PVA-chains for 2 hours to crosslink the telechelic aldehydic PVA-chains and form the PVA-coated MBs at the water-air interface. CACTUS MBs were synthesized in a similar fashion to the above, but adding gold nanoparticles (diameter 1.9nm, Nanoprobes, NY, USA) during formation of the MBs.The size distributions of MBs and CACATUS MBs were determined using an optical microscope (ECLIPSE Ci-S, Nikon, Tokyo, Japan) and a Neubauer counting chamber (Brand GmbH, Wertheim, Germany).The acoustic attenuation coefficients of the MBs suspension were acquired at peak negative pressure (PNP) from 10 - 300 kPa. Three MBs suspension samples with concentrations of (sample A), (sample B) and ml-1 (sample C) were prepared and loaded in a 1 cm thick two-cavity chamber. A flat single crystal ultrasound transducer with central frequency 3.5MHz was used to generate the ultrasound beam. The amplitude of received echoes through samples and water were compared at the fundamental frequency, as well as the 2nd and 3rd harmonic for each value of the concentration used.The mass attenuation of water, suspension of gold nanoparticles with concentration 160mg/L, plain MBs, and CACTUS MBs, was measured by quantum FX-CT micro-CT (PerkinElmer Inc, MA, USA). The micro-CT was operated at a current of 200mA with exposure time of 120s and varied voltage 50kV, 70kV and 90kV. Each 3D image has a size of 512*512*512 pixels or 75.8*75.8*75.8 mm. Contrast to noise ratios (CNR) between water and all samples were calculated following Eq. 1.Where S(x,y,z) and W(x,y,z) are the mass attenuation of the sample and water per voxel, respectively. ns(x,y,z) and nw(x,y,z) are the noise function with zero mean of sample and water respectively. Ms and Mw are the mean mass attenuation acquired for the sample and water in the volume of interest. The σs2 and σw2 are the variance of the mass attenuation read out of the sample and water in the volume of interested.In addition to the gas-core MBs for the CT tests, liquid-core gold loaded capsules were synthesized in two steps. In the first step, PVA shelled liquid-core capsules were obtained by exposing MBs to 66% v/v ethanol solution. In the second step, the resulting liquid-core capsules were mixed with high concentration gold nanoparticles suspension and homogenized by a shaker (MS 3 basic, IKA, Königswinter Germany) at 500rpm for 1 hour for goal loading. The resulting gold loaded capsules were washed with Milli-Q water using centrifuge (Galaxy 5D digital microcentrifuge, VWR, USA) at a speed of 1000 g for 5 min.Results and discussionThe mean diameter of MBs is 3.6±1.1 μm. The mean diameter of CACTUS MBs is 3.2±0.7 μm. The size distribution of the gold loaded capsules was not investigated separately, but rather assumed identical to the plain MBs. The number and the volume distribution of MBs and CACTUS MBs are shown in figure 1. The results demonstrate that most of the CACTUS MBs and MBs have a diameter from 1 to 6 μm. Therefore, they are able pass through the capillaries and will resonate within typical clinical diagnostic ultrasound frequency below 15 MHz.Pressure dependent acoustic attenuation coefficients of the sample A, B, and C are shown in figure 2. The results show that attenuation coefficients of sample A and B at the fundamental frequency stay constant and slightly increase at the second harmonic at the PNP below 100kPa, indicating a linear oscillation of MBs. As the PNP reaches 200kPa, the attenuation coefficient of sample A at fundamental frequency decreases while at 2nd and 3rd harmonics increases, indicating that the energy of the echo shifts from the fundamental frequency to the 2nd and 3rd harmonics. As the PNP goes higher to 300kPa, the attenuation coefficient of sample A at the fundamental frequency, 2nd, and 3rd harmonics decreases, suggesting that the energy shifts to an even higher harmonic. At the same time, the attenuation coefficient of sample B stays constant at fundamental frequency, decreases at 2nd harmonics, and increases at the 3rd harmonic, suggesting the energy starts to shift to the 3rd harmonic. The attenuation coefficient of sample C at fundamental frequency, 2nd and 3rd harmonics keep constant and low due to low sample concentration. The test reveals the energy shifting of the echo to the higher harmonics at PNP higher than 100 kPa, indicating the nonlinear oscillation of MBs at PNP higher than 100 kPa. Moreover, the concentration of the MBs seems to influence the energy shifting: the higher the concentration the earlier the shift to the higher harmonics occurs, in the range of the concentration consider in this study.The pilot results of the micro-CT tests are presented in Table 1. The reference, gold nanoparticles solution, has the highest CNR per voxel at all CT operating voltages. The CNR per voxel of CACTUS MBs suspensions is below 0.1, virtually equaling the MBs at all operating voltages, suggesting that no gold or very little gold were loaded into the shell of the CACTUS MBs. The gold loaded capsules suspension has higher CNR per voxel than the capsule supernatant (the surrounding environment of capsules) and the MBs suspension, implying that the gold nanoparticles were loaded into the capsules. However, it is not clear whether the gold nanoparticles were loaded in the core of the MBs or in the MBs shell. The expected sharp increase of CNR per voxel at the k-edge of gold did not appear. We believe that is because even at our highest operating voltage of 90kV, the percentage of the photons with energy higher than 80.7 keV is still low. Introduction of a high-pass metal filter could increase the percentage of high energy photon. On the other hand, the metal filter will reduce the total number of the photons which would increase the noise of the images. Since same current was applied on every CT test, less X-ray photons reached the sensors when the CT was operated at low voltage. Therefore, it might be worth performing additional calibration tests to adjust the operating currents to make sure that the numbers of the photons that reach the sensor at every operating voltage are the same.ConclusionIn this study, the CACTUS MBs and gold loaded capsules were fabricated as potential candidates for dual modal contrast agent. The characterization revealed that gold loaded capsule is a promising initial step. Nevertheless, the method to convert back liquid-core capsules to gas-core MBs needs to be established.[1] Cavalieri, F., El Hamassi, A., Chiessi, E., Paradossi, G., Villa, R., & Zaffaroni, N. (2006). Tethering functional ligands onto shell of ultrasound active polymeric microbubbles. Biomacromolecules, 7(2), 604-611.
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| 6. |
- Forsum, Elisabet, et al.
(author)
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MET-values of standardised activities in relation to body fat: studies in pregnant and non-pregnant women
- 2018
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In: Nutrition & Metabolism. - : BIOMED CENTRAL LTD. - 1743-7075. ; 15
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Journal article (peer-reviewed)abstract
- Background: Physical activity is associated with health in women. Published MET-values (MET: metabolic equivalent of task) may assess physical activity and energy expenditure but tend to be too low for subjects with a high total body fat (TBF) content and therefore inappropriate for many contemporary women. The MET-value for an activity is the energy expenditure of a subject performing this activity divided by his/her resting energy expenditure, often assumed to be 4.2 kJ/kg/h. Relationships between TBF and MET have been little studied although overweight and obesity is common in women. Available data indicate that MET-values decrease during pregnancy but more studies in pregnant contemporary women are needed. Subjects and methods: Using indirect calorimetry we measured energy expenditure and assessed MET-values in women, 22 non-pregnant (BMI: 18-34) and 22 in gestational week 32 (non-pregnant BMI: 18-32) when resting, sitting, cycling (30 and 60 watts), walking (3.2 and 5.6 km/h) and running (8 km/h). Relationships between TBF and MET-values were investigated and used to predict modified MET-values. The potential of such values to improve calculations of total energy expenditure of women was investigated. Results: The resting energy expenditure was below 4.2 kJ/kg/h in both groups of women. Women in gestational week 32 had a higher resting energy metabolism (p amp;lt; 0.001) and 7-15% lower MET-values (p amp;lt; 0.05) than non-pregnant women. MET-values of all activities were correlated with TBF (p amp;lt; 0.05) in non-pregnant women and modified MET-values improved estimates of total energy expenditure in such women. In pregnant women, correlations (p amp;lt;= 0.03) between TBF and MET were found for running (8 km/h) and for walking at 5.6 km/h. Conclusions: Our results are relevant when attempts are made to modify the MET-system in contemporary pregnant and non-pregnant women. MET-values were decreased in gestational week 32, mainly due to an increased resting energy metabolism and studies describing how body composition affects the one MET-value (i.e. the resting energy metabolism in kJ/kg/h) during pregnancy are warranted. Studies of how pregnancy and TBF affect MET-values of high intensity activities are also needed. Corrections based on TBF may have a potential to improve the MET-system in non-pregnant women.
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| 7. |
- Fröberg, Asa, et al.
(author)
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High variability in strain estimation errors when using a commercial ultrasound speckle tracking algorithm on tendon tissue
- 2016
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In: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 57:10, s. 1223-1229
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Journal article (peer-reviewed)abstract
- Background: Ultrasound speckle tracking offers a non-invasive way of studying strain in the free Achilles tendon where no anatomical landmarks are available for tracking. This provides new possibilities for studying injury mechanisms during sport activity and the effects of shoes, orthotic devices, and rehabilitation protocols on tendon biomechanics. Purpose: To investigate the feasibility of using a commercial ultrasound speckle tracking algorithm for assessing strain in tendon tissue. Material and Methods: A polyvinyl alcohol (PVA) phantom, three porcine tendons, and a human Achilles tendon were mounted in a materials testing machine and loaded to 4% peak strain. Ultrasound long-axis cine-loops of the samples were recorded. Speckle tracking analysis of axial strain was performed using a commercial speckle tracking software. Estimated strain was then compared to reference strain known from the materials testing machine. Two frame rates and two region of interest (ROI) sizes were evaluated. Results: Best agreement between estimated strain and reference strain was found in the PVA phantom (absolute error in peak strain: 0.21 +/- 0.08%). The absolute error in peak strain varied between 0.72 +/- 0.65% and 10.64 +/- 3.40% in the different tendon samples. Strain determined with a frame rate of 39.4Hz had lower errors than 78.6Hz as was the case with a 22mm compared to an 11mm ROI. Conclusion: Errors in peak strain estimation showed high variability between tendon samples and were large in relation to strain levels previously described in the Achilles tendon.
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| 8. |
- Gharehbaghi, Arash, et al.
(author)
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A novel method for discrimination between innocent and pathological heart murmurs
- 2015
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In: Medical Engineering and Physics. - : Elsevier. - 1350-4533 .- 1873-4030. ; 37:7, s. 674-682
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Journal article (peer-reviewed)abstract
- This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.
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| 9. |
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| 10. |
- Grishenkov, Dmitry, 1983-, et al.
(author)
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In search of the optimal ultrasound heart perfusion imaging platform
- 2015
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In: Journal of ultrasound in medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 34:9, s. 1599-1605
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Journal article (peer-reviewed)abstract
- ObjectiveQuantification of the myocardial perfusion by contrast echocardiography (CEC) remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled.MethodsTo contribute towards an improvement, we developed a CEC perfusion imaging platform based on isolated rat heart coupled to the ultrasound scanner. Perfusion was assessed using three different types of contrast agent: dextran-based Promiten®, phospholipid-shelled SonoVue®, and polymer-shelled MB-pH5-RT. The myocardial video-intensity was monitored over time from contrast administration to peak and two characteristic constants were calculated using exponential fit (A representing capillary volume and b representing inflow velocity).ResultsAcquired experimental evidence demonstrates that the application of all three types of contrast agent allow ultrasonic estimation of myocardial perfusion in the isolated rat heart. Video-intensity maps show that an increase in contrast concentration increases the late plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to Axb, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by the flowmeter attached to the aortic cannula.ConclusionsThe described CEC perfusion imaging platform holds promise for standardized evaluation and optimization of ultrasound contrast perfusion imaging where real time inflow curves at low acoustic power semi-quantitatively reflect coronary flow.
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