Changes In Relative Concentrations Research Articles

High resolution LiDAR measurements reveal fine internal structure and variability of sediment-carrying coastal plume

We report results of a field survey conducted in the buoyant, sediment-carrying coastal plume generated by the discharge from the Patos Lagoon, the World's largest choked lagoon. The concentration of total suspended matter (TSM) and organic matter (as represented by total organic carbon, TOC) were mapped using an ultraviolet fluorescent LiDAR, which allowed for extensive data coverage (total of 79,387 simultaneous determinations of TSM and TOC) during 3 consecutive days. These observations were accompanied by hydrographic measurements from the ship and at a mooring station. We first describe synoptic variability of the plume, which responded energetically to wind forcing. We then analyze the TSM, TOC and hydrographic data jointly and develop a simple approach to estimate the rates of suspended matter removal from the upper layer due to gravitational settling and turbulent mixing based on relative changes in TSM and TOC concentrations. Four distinct regions within the plume exhibiting different dynamics of suspended and dissolved constituents were identified on this basis.

How global is FDI? Evidence from the analysis of Theil indices

It is open to question whether the intensified worldwide competition for FDI has reduced its traditionally strong concentration in a few large and relatively advanced host countries. We calculate and decompose Theil indices to track changes in absolute and relative concentration of FDI during the period 1970–2013. We find that both absolute and relative concentration decreased when excluding offshore financial centers from the overall sample. In addition to the narrowing gap between OECD and non-OECD countries, the concentration across non-OECD countries declined for both the absolute and relative measures. This is also true for major subgroups of non-OECD countries. Finally, recent developments indicate that low-income countries are no longer at the losing end of the competition for FDI.

FNIRS differentiates cognitive workload between concussed adolescents and healthy controls

fNIRS differentiates cognitive workload between concussed adolescents and healthy controls

Cognitive workload as the physiologic basis for symptom provocation with task performance in concussion: an fNIRS study of prefrontal brain activity

Cognitive workload as the physiologic basis for symptom provocation with task performance in concussion: an fNIRS study of prefrontal brain activity

Functional Near-Infrared Spectroscopy in Athletes Pre- and Post-Season Demonstrates Consistent Pattern of Frontal Cortical Activation with King-Devick Testing

Functional Near-Infrared Spectroscopy in Athletes Pre- and Post-Season Demonstrates Consistent Pattern of Frontal Cortical Activation with King-Devick Testing

Issues in quantification of registered respiratory gated PET/CT in the lung

PET/CT quantification of lung tissue is limited by several difficulties: the lung density and local volume changes during respiration, the anatomical mismatch between PET and CT and the relative contributions of tissue, air and blood to the PET signal (the tissue fraction effect). Air fraction correction (AFC) has been shown to improve PET image quantification in the lungs. Methods to correct for the movement and anatomical mismatch involve respiratory gating and image registration techniques. While conventional registration methods only account for spatial mismatch, the Jacobian determinant of the deformable registration transformation field can be used to estimate local volume changes and could therefore potentially be used to correct (i.e. Jacobian Correction, JC) the PET signal for changes in concentration due to local volume changes. This work aims to investigate the relationship between variations in the lung due to respiration, specifically density, tracer concentration and local volume changes. In particular, we study the effect of AFC and JC on PET quantitation after registration of respiratory gated PET/CT patient data. Six patients suffering from lung cancer with solitary pulmonary nodules underwent F-FDG PET/cine-CT. The PET data were gated into six respiratory gates using displacement gating based on a real-time position management (RPM) signal and reconstructed with matched gated CT. The PET tracer concentration and tissue density were extracted from registered gated PET and CT images before and after corrections (AFC or JC) and compared to the values from the reference images. Before correction, we observed a linear correlation between the PET tracer concentration values and density. Across all gates and patients, the maximum relative change in PET tracer concentration before (after) AFC was found to be 16.2% (4.1%) and the maximum relative change in tissue density and PET tracer concentration before (after) JC was found to be 17.1% (5.5%) and 16.2% (6.8%) respectively. Overall our results show that both AFC or JC largely explain the observed changes in PET tracer activity over the respiratory cycle. We also speculate that a second order effect is related to change in fluid content but this needs further investigation. Consequently, either AFC or JC is recommended when combining lung PET images from different gates to reduce noise.

'25-Hydroxyvitamin D, Autoantigenic and Total Antibody Concentrations: Results from a Danish Case-control Study of Newly Diagnosed Patients with Childhood Type 1 Diabetes and their Healthy Siblings'.

B cells have recently entered the stage as an important accessory player in type 1 diabetes (T1D) etiopathogenesis. Experimental studies suggest regulatory functions of vitamin D on B cells. However, only a few human studies, with considerable methodological limitations, have been conducted within this field. Our objective was to investigate whether higher 25-hydroxyvitamin D (25(OH)D) concentrations were inversely associated with β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma-associated antigen-2A (IA-2A). Further, we also wanted to examine the relationship between 25(OH)D and total antibody concentrations. We randomly selected 500 patients with newly diagnosed T1D and 500 siblings for 25(OH)D, antibody and genetic analysis from the population-based Danish Registry of Childhood and Adolescent Diabetes. The relative change (RC) in the mean concentration of GADA, IA-2A and antibody isotypes by a 10nmol/l increase in 25(OH)D concentration was modelled by a robust log-normal regression model. We found no association between 25(OH)D and GADA [adjusted RC per 10nmol/l increase: 1.00; 95% confidence interval (CI): 0.98-1.02] and IA-2A [adjusted RC per 10nmol/l increase: 0.92; CI: 0.76-1.12]. Further, 25(OH)D was not associated with the total concentration of antibody isotypes [immunoglobulin (Ig)A, IgE, IgG and IgM]. All null findings were unaltered after adjustment for genetic variation in the vitamin D pathway. Physiological concentrations of 25(OH)D are unlikely to have a clinically important effect on antibody concentrations in a paediatric population of newly diagnosed patients with T1D and their healthy siblings.

The suburbanisation of poverty in British cities, 2004-16: extent, processes and nature

ABSTRACTThis paper tracks changes in relative centralisation and relative concentration of poverty for the 25 largest British cities, analysing change for poor and non-poor groups separately, and examining parallel changes in spatial segregation. The paper confirms that poverty is suburbanising, at least in the larger cities, although poverty remains over-represented in inner locations. Suburbanisation is occurring through both the reduction in low income populations in inner locations and the growth non-poor groups in these places, consistent with a process of displacement. Relative centralisation of poverty has fallen more stronglythan relative concentration of poverty, as the outward shift of poorer groups leaves them still living in denser neighbourhoods on average. The paper also shows that spatial segregation (unevenness) declined at the same time although it remains to be seen whether this indicates a long-term shift to less segregated urban forms or a transitional outcome before new forms of segregation emerge around suburban poverty concentrations.

Imperial College near infrared spectroscopy neuroimaging analysis framework.

This paper describes the Imperial College near infrared spectroscopy neuroimaging analysis (ICNNA) software tool for functional near infrared spectroscopy neuroimaging data. ICNNA is a MATLAB-based object-oriented framework encompassing an application programming interface and a graphical user interface. ICNNA incorporates reconstruction based on the modified Beer-Lambert law and basic processing and data validation capabilities. Emphasis is placed on the full experiment rather than individual neuroimages as the central element of analysis. The software offers three types of analyses including classical statistical methods based on comparison of changes in relative concentrations of hemoglobin between the task and baseline periods, graph theory-based metrics of connectivity and, distinctively, an analysis approach based on manifold embedding. This paper presents the different capabilities of ICNNA in its current version.

Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems.

Introduction:Gaseous microemboli (GME) introduced during cardiac surgery are considered as a potential source of morbidity, which has driven the development of the first bubble counters. Two new generation bubble counters, introduced in the early 2000s, claim correct sizing and counting of GME. This in-vitro study aims to validate the accuracy of two bubble counters using monodisperse bubbles in a highly controlled setting at low GME concentrations.Methods:Monodisperse GME with a radius of 43 µm were produced in a microfluidic chip. Directly after their formation, they were injected one-by-one into the BCC200 and the EDAC sensors. GME size and count, measured with the bubble counters, were optically verified using high-speed imaging.Results:During best-case scenarios or low GME concentrations of GME with a size of 43 µm in radius in an in-vitro setup, the BCC200 overestimates GME size by a factor of 2 to 3 while the EDAC underestimates the average GME size by at least a factor of two. The BCC200 overestimates the GME concentration by approximately 20% while the EDAC overestimates the concentration by nearly one order of magnitude. Nevertheless, the calculated total GME volume is only over-predicted by a factor 2 since the EDAC underestimates the actual GME size. For the BCC200, the total GME volume was over-predicted by 25 times due to the over-estimation of GME size.Conclusions:The measured errors in the absolute sizing/counting of GME do not imply that all results obtained using the bubble counters are insignificant or invalid. A relative change in bubble size or bubble concentration can accurately be measured. However, care must be taken in the interpretation of the results and their absolute values. Moreover, the devices cannot be used interchangeably when reporting GME activity. Nevertheless, both devices can be used to study the relative air removal characteristics of CPB components or for the quantitative monitoring of GME production during CPB interventions.

Prefrontal activation during a working memory task differs between patients with unipolar and bipolar depression: A preliminary exploratory study

BackgroundTo identify bipolar disorder during the initial stages of a depressive episode has always been a great clinical challenge. Patterns of functional brain activity may underlie the differences in the neural mechanisms of bipolar depression (BD) and unipolar depression (UD). This study aimed to investigate the differences in neural activity between BD and UD patients during executive task. MethodsWe performed a 52-channel near-infrared spectroscopy (NIRS) scan in 39 patients with BD, 35 patients with UD, and 36 healthy controls (HCs). The relative concentration changes in oxygenated hemoglobin ([oxy-Hb]) and deoxygenated hemoglobin ([deoxy-Hb]) during a 1-back working memory task were measured for each channel. Clinical characteristics including current mood were evaluated within one week prior to NIRS examination. ResultsCompared to HCs, BD (CH34: Z = −2.354, P = 0.019) and UD patients (CH18: Z = −2.358, P = 0.018; CH30: Z = −2.174, P = 0.030; CH34: Z = −1.990, P = 0.047) showed reduced activation of [oxy-Hb] in the inferior prefrontal region. Compared to patients with UD, patients with BD showed less decreased [oxy-Hb] changes in the left frontopolar cortex (FPC) (CH18: Z = −2.366, P = 0.018), left pars opercularis and pars triangularis (POPE/PTRI) regions (Broca's area) (CH30: Z = −2.333, P = 0.020). No correlation existed between clinical characteristics and NIRS measurements. LimitationsThe effect of medication could not be excluded, and behavioral data was not systematically collected. ConclusionThe results from this preliminary exploratory study suggest distinct prefrontal activation patterns underlie BD and UD, especially in the left frontopolar region and Broca's area. The NIRS-based prefrontal activation measurement may serve as a potential marker to aid in differentiating bipolar from unipolar depression.

Gadolinium-enhanced 7.0 T magnetic resonance imaging assessment of the aqueous inflow in rat eyes in vivo

The goal of this study was to calculate the anterior chamber volume and assess aqueous inflow in rat eyes in vivo, under anesthetic condition. Gadolinium-contrast agent (Gd-DTPA, 234.5 mg/ml) was administered to Sprague−Dawley rat eyes via anterior chamber injection or instillation of 234.5 or 117.25 mg/ml Gd-DTPA in 0.2% azone as eye drops, and changes of Gd signal visualized by 7.0 T magnetic resonance imaging (MRI). The safety of local application of Gd-DTPA and azone were performed after MRI scanning. The anterior chamber injection of Gd-DTPA (234.5 mg/ml) group was used for anterior chamber volume and aqueous inflow calculating. Serial changes in Gd-DTPA relative concentration in the anterior chamber was determined based on the initial Gd signal gray values and the initial relative concentration of Gd-DTPA after anterior chamber Gd-DTPA injection. The mean aqueous inflow in rat eyes in vivo was assessed based on changes in Gd-DTPA relative concentration and the anterior chamber volume. Eye drops of Gd-DTPA (234.5 mg/ml) in 0.2% azone readily allowed safe assessment of the aqueous inflow by 7.0 T MRI. Under anesthetic condition in vivo, the mean anterior chamber volume (ACV) in rats was 8493.6 ± 657.4 μm3, no differences were observed in the aqueous inflow measured by topical instillation of 234.5 mg/ml Gd-DTPA in 0.2% azone (0.182 ± 0.011 μl/min) between that measured by anterior chamber injection (0.165 ± 0.041 μl/min, P > 0.05), Timolol reduced aqueous inflow to 0.124 ± 0.020 μl/min (P < 0.05). Our results indicated that Gd-enhanced 7.0 T MRI allows evaluation of the Gd signal variation and anterior chamber volume in rats in vivo. The aqueous inflow calculation via non-invasive local application of 234.5 mg/ml Gd-DTPA can be assessed by the variability of relative concentration of Gd-DTPA in anterior chamber and ACV in vivo, under anesthetic condition.

Repetition suppression in aging: A near-infrared spectroscopy study on the size-congruity effect

Age-related changes in the hemodynamic response regarding inhibition capacity and repetition suppression were examined using a modified version of the numerical Stroop task. Young (20–38 yrs; M = 28 yrs; N = 18), middle-aged (47–59 yrs; M = 52 yrs; N = 17), and older participants (60–78 yrs; M = 69 yrs; N = 19) solved a physical and numerical version of the size-congruity task, in which trials from the same experimental condition were presented in triplets. Response times revealed a strong Stroop effect in both tasks (faster reaction times during neutral than during incongruent trials) and increased with participants’ age. Reaction times decreased with item repetition. In line with previous studies, the hemodynamic response (relative concentration changes in oxygenated and deoxygenated hemoglobin) assessed with near-infrared spectroscopy was comparable across incongruent and neutral trials. Strong repetition suppression of the oxygenated hemoglobin response was observed in frontal brain regions as well as in the left parietal region in all age groups. In middle and right parietal regions, repetition suppression decreased with age and was absent among older participants. These results indicate a reduced adaptation of the hemodynamic response in middle and right parietal regions of older individuals’ brains in response to repeated interference control.

Photoplethysmography for blood volumes and oxygenation changes during intermittent vascular occlusions

Photoplethysmography (PPG) is an optical technique that measures blood volume variations. The main application of dual-wavelength PPG is pulse oximetry, in which the arterial oxygen saturation (SpO_2) is calculated noninvasively. However, the PPG waveform contains other significant physiological information that can be used in conjunction to SpO_2 for the assessment of oxygenation and blood volumes changes. This paper investigates the use of near infrared spectroscopy (NIRS) processing techniques for extracting relative concentration changes of oxygenated (DeltaHbO_2), reduced (DeltaHHb) and total haemoglobin (DeltatHb) from dual-wavelength PPG signals during intermittent pressure-increasing vascular occlusions. A reflectance PPG sensor was attached on the left forearm of nineteen (n = 19) volunteers, along with a reference NIRS sensor positioned on the same forearm, above the left brachioradialis. The investigation protocol consisted of seven intermittent and pressure-increasing vascular occlusions. Relative changes in haemoglobin concentrations were obtained by applying the modified Beer–Lambert law to PPG signals, while oxygenation changes were estimated by the difference between red and infrared attenuations of DC PPGs (A_{Ox} = DeltaA_{IR} − DeltaA_R) and by the conventional SpO_2. The DeltaHbO_2, DeltaHHb, DeltatHb from the PPG signals indicated significant changes in perfusion induced by either partial and complete occlusions (p < 0.05). The trends in the variables extracted from PPG showed good correlation with the same parameters measured by the reference NIRS monitor. Bland and Altman analysis of agreement between PPG and NIRS showed underestimation of the magnitude of changes by the PPG. A_{Ox} indicated significant changes for occlusion pressures exceeding 20 mmHg (p < 0.05) and correlation with tissue oxygenation changes measured by NIRS, while SpO_2 had significant changes after 40 mmHg (p < 0.05). Relative changes in haemoglobin concentrations can be estimated from PPG signals and they showed a good level of accuracy in the detection of perfusion and oxygenation changes induced by different degrees of intermittent vascular occlusions. These results can open up to new applications of the PPG waveform in the detection of blood volumes and oxygenation changes.

Sensitivity study of cloud parameterizations with relative dispersion in CAM5.1: impacts on aerosol indirect effects

Abstract. Aerosol-induced increase of relative dispersion of cloud droplet size distribution ε exerts a warming effect and partly offsets the cooling of aerosol indirect radiative forcing (AIF) associated with increased droplet concentration by increasing the cloud droplet effective radius (Re) and enhancing the cloud-to-rain autoconversion rate (Au) (labeled as the dispersion effect), which can help reconcile global climate models (GCMs) with the satellite observations. However, the total dispersion effects on both Re and Au are not fully considered in most GCMs, especially in different versions of the Community Atmospheric Model (CAM). In order to accurately evaluate the dispersion effect on AIF, the new complete cloud parameterizations of Re and Au explicitly accounting for ε are implemented into the CAM version 5.1 (CAM5.1), and a suite of sensitivity experiments is conducted with different representations of ε reported in the literature. It is shown that the shortwave cloud radiative forcing is much better simulated with the new cloud parameterizations as compared to the standard scheme in CAM5.1, whereas the influences on longwave cloud radiative forcing and surface precipitation are minimal. Additionally, consideration of the dispersion effect can significantly reduce the changes induced by anthropogenic aerosols in the cloud-top effective radius and the liquid water path, especially in the Northern Hemisphere. The corresponding AIF with the dispersion effect considered can also be reduced substantially by a range of 0.10 to 0.21 W m−2 at the global scale and by a much bigger margin of 0.25 to 0.39 W m−2 for the Northern Hemisphere in comparison with that of fixed relative dispersion, mainly dependent on the change of relative dispersion and droplet concentrations (Δε∕ΔNc).

Effect of Exercise Training on Cerebral Microcirculation in Men with and without Type 1 Diabetes

PURPOSE: Effects of regular exercise on cerebral microcirculation in diabetes are unknown. We examined if exercise training leads to similar adaptations in cerebral microcirculation in men with and without type 1 diabetes (T1D). METHODS: Eight men with T1D (33±6 yrs) and eight healthy men (HC; 38±7 yrs) matched for age, anthropometry, and peak O2 uptake (VO2peak) (p>0.05), completed a 1-year individualized exercise training intervention. Individually collected data on training were similar in T1D vs. HC (mean±SD per month; p>0.05): 13±4 vs. 15±6 endurance training sessions, 3±1 vs. 3±3 resistance training sessions, 57±5 vs. 55±8 % of heart rate reserve, 16:58±6:07 vs. 16:52±4:39 h:min, 7759±4540 vs. 7762±3812 kcal, respectively. Before and after the intervention, the subjects performed step incremental cycling exercise to volitional fatigue. During exercise, alveolar gas exchange (mass spectrometry) and normalized relative concentration changes in deoxygenated hemoglobin (%Δ[HHb]) in the prefrontal cerebral cortex (near-infrared spectroscopy) were monitored; %Δ[HHb] reflects imbalance between local O2 delivery and utilization. RESULTS: Training increased VO2peak and peak work rate similarly in T1D (45±5 to 49±6 mL/min/kg fat-free mass [FFM], p<0.01; 237±34 to 254±27 W, p<0.05) and HC (48±3 to 52±5 mL/min/kg FFM, p<0.05; 255±17 to 282±36 W, p<0.05). Training also decreased minute ventilation at 160W (in T1D and HC) and 200W (in HC) (p<0.05) but had no effect on end-tidal CO2 partial pressure, which estimates arterial CO2 pressure affecting cerebral blood flow. Cerebral %Δ[HHb] did not change at any work rate in T1D but decreased at 200W in HC (p<0.05). No differences were observed between T1D and HC in the reported parameters before the intervention. CONCLUSION: Exercise training did not improve exercise-induced imbalance between local O2 delivery and utilization in prefrontal microcirculation in T1D but did so at high exercise intensity (200 W) in HC. This between-group difference was not due to different respiratory adaptations and must thus be explained by other diabetes-related mechanisms (e.g., impaired cerebrovascular autoregulation, CO2 reactivity, or neocapillarization) influencing cerebral blood flow. Supported by: Tekes, Ministry of Education and Culture, Finnish Medical Foundation.

The global concentration of wealth

This paper compares changes in relative and absolute wealth concentrations to establish whether both processes have followed similar trajectories. The findings indicate that while the relative wealth concentration level has increased in recent times, it is not extraordinarily high from a historical perspective. In contrast, the absolute wealth concentration level is most likely higher than has ever previously occurred, due to the growth of per capita wealth holdings and the population size of high net worth individuals (HNWIs). The available data also suggest that HNWIs recovered very quickly from the losses that they experienced in the financial crisis of 2008. As a result, HNWIs’ wealth holdings in 2013 were at least 30% higher than they were in 2007. The post-crisis recovery of billionaires was even stronger, with their 2014 net wealth holdings more than 85% higher than 2007 levels.

Accelerated point of muscle deoxygenation during the 20-m shuttle run test.

This study examined whether the point of accelerated deoxygenation of active muscle occurs during the 20-m shuttle run test (20mSRT) and, if so, whether it is associated with exercise performance in the test. Twenty-nine male subjects performed the 20mSRT, and concentration changes in oxyhaemoglobin (ΔOxy-Hb) and deoxyhaemoglobin (ΔDeoxy-Hb) in the m. vastus lateralis were measured using a portable near-infrared spectroscopy device. The difference between the relative concentration changes in ΔOxy-Hb and ΔDeoxy-Hb (Δ[Oxy-Hb-Deoxy-Hb]) was regarded as the muscle oxygenation index. Group-averaged Δ[Oxy-Hb-Deoxy-Hb] showed progressive decrease during the test. However, among the individuals, we found an accelerated point of decrease in Δ[Oxy-Hb-Deoxy-Hb] in 20 subjects, which revealed that the laps at the accelerated point correlated with the total laps (r=0·78). These results demonstrate that the accelerated deoxygenation of active muscle occurs during the 20mSRT, but not in all cases. Our findings also indicate that if the accelerated point of muscle deoxygenation occurs, the timing of its appearance is related to 20mSRT performance.

High Energy Expenditure and Negative Energy Balance Modulate Composition and Metabolism of the Gut Microbiota

Dietary intake and acute physiologic stress may modulate health in part by influencing interactions between the gut microbiome and host, but these relationships remain poorly characterized. This study explored relationships between gut microbiota composition and activity, and diet, gastrointestinal permeability and inflammation in Soldiers participating in a 4‐d, 51 km cross‐country ski march (SKI) characterized by high energy expenditure (6155 ± 515 kcal/d) and negative energy balance (2.7 ± 1.2 kg weight loss). During SKI, 73 Soldiers (20 ± 1 yr, BMI 23 ± 2 kg/m2) were provided 3 combat rations/d, or 3 rations/d supplemented with 1000 kcal/d from protein‐ or carbohydrate‐based snacks generating variability in energy, protein and carbohydrate intakes. Stool, blood and urine samples were collected from 26 Soldiers before and after SKI. Stool was analyzed for bacterial composition by 16S rDNA sequencing, and global metabolite profiling by UPLC‐MS/MS. Gastrointestinal permeability was assessed by dual sugar absorption test, and plasma lipopolysaccharide (LPS) and serum IL‐6 were measured as markers of microbial translocation and inflammation, respectively. Ordination, cluster and classification analyses of gut microbiota composition data indicated a pronounced alteration of gut microbiota composition during SKI independent of diet group. This effect was characterized by a more heterogeneous distribution of taxa abundances within samples following SKI (Shannon index, P = 0.04), and changes in the relative abundance of &gt;50% of identified genera (Q &lt; 0.10). Changes included increases in the relative abundance of several potentially deleterious and infectious genera, and decreases in the relative abundance of several genera thought to deter pathogen invasion, reduce inflammation and promote immunity. Prediction models linked changes in gut microbiota composition to 69 of 299 metabolites that were significantly altered in stool, with decreases in amino acid and nucleotide metabolites comprising the majority. Univariate analyses generally did not detect associations between changes in taxa relative abundance or concentrations of bacterially‐associated metabolites and energy or macronutrient intake, changes in gastrointestinal permeability, or changes in LPS and IL‐6 concentrations. These findings demonstrate pronounced changes in gut microbiota composition and metabolism in response to a multi‐stressor environment that appear to be independent of energy and macronutrient intakes within the ranges studied. The implications for health remain to be determined. The views expressed in this abstract are those of the authors and do not reflect official policy of the Dept. of Army, Dept. of Defense, or US Government.Support or Funding InformationFunded by US Army Medical Research and Material Command, the US Defense Health Program, and the Norwegian Defense Research Establishment agreement NO. W81XWH‐12‐0279.

Predicting tenocyte expression profiles and average molecular concentrations in Achilles tendon ECM from tissue strain and fiber damage.

In this study, we propose a method for quantitative prediction of changes in concentrations of a number of key signaling, structural and effector molecules within the extracellular matrix of tendon. To achieve this, we introduce the notion of elementary cell responses (ECRs). An ECR defines a normal reference secretion profile of a molecule by a tenocyte in response to the tenocyte's local strain. ECRs are then coupled with a model for mechanical damage of tendon collagen fibers at different straining conditions of tendon and then scaled up to the tendon tissue level for comparison with experimental observations. Specifically, our model predicts relative changes in ECM concentrations of transforming growth factor beta, interleukin 1 beta, collagen type I, glycosaminoglycan, matrix metalloproteinase 1 and a disintegrin and metalloproteinase with thrombospondin motifs 5, with respect to tendon straining conditions that are consistent with the observations in the literature. In good agreement with a number of in vivo and in vitro observations, the model provides a logical and parsimonious explanation for how excessive mechanical loading of tendon can lead to under-stimulation of tenocytes and a degenerative tissue profile, which may well have bearing on a better understanding of tendon homeostasis and the origin of some tendinopathies.