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We derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell-cell and cell-scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction-diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities, and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large-time: linear, logarithmic and stationary. Employing travelling wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.

We derive a multiphase, moving boundary model to represent the development of tissue in vitro in a porous tissue engineering scaffold. We consider a cell, extra-cellular liquid and a rigid scaffold phase, and adopt Darcy’s law to relate the velocity of the cell and liquid phases to their respective pressures. Cell–cell and cell–scaffold interactions which can drive cellular motion are accounted for by utilising relevant constitutive assumptions for the pressure in the cell phase. We reduce the model to a nonlinear reaction–diffusion equation for the cell phase, coupled to a moving boundary condition for the tissue edge, the diffusivity being dependent on the cell and scaffold volume fractions, cell and liquid viscosities and parameters that relate to cellular motion. Numerical simulations reveal that the reduced model admits three regimes for the evolution of the tissue edge at large time: linear, logarithmic and stationary. Employing travelling-wave and asymptotic analysis, we characterise these regimes in terms of parameters related to cellular production and motion. The results of our investigation allow us to suggest optimal values for the governing parameters, so as to stimulate tissue growth in an engineering scaffold.

Background: Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness. Methods: We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. Results: 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Conclusion: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection. Trial Registration: ClinicalTrials.gov number, NCT04416399 Funding: Oxford NIHR Biomedical Research Centre and AstraZeneca Declaration of Interests: Dr. Ramakrishnan reports grants and non-financial support from Oxford Respiratory NIHR BRC, during the conduct of the study; non-financial support from AstraZeneca, personal fees from Australian Government Research Training Program, outside the submitted work; . Dr. Nicolau has nothing to disclose. Mrs Langford has nothing to disclose. Mr. Mahdi has nothing to disclose. Mrs Helen Jeffers reports personal fees from AstraZeneca, outside the submitted work; . Miss Mwasuku has nothing to disclose. Mrs Krassowska has nothing to disclose. Dr Fox has nothing to disclose. Dr Binnian has nothing to disclose. Dr Glover has nothing to disclose. Dr Bright has nothing to disclose. Dr. Butler reports grants from National Institute for Health Research (NIHR), Roche Molecular Diagnostics, Janssen Pharmaceuticals, and various public funding bodies for research related to diagnostics and infections. He has revcied personal fees from Pfizer INC, Roche Diagnostics, and Janssen Pharmaceuticals, outside the submitted work. Dr. Cane has nothing to disclose. Mr. Halner has nothing to disclose. Dr. Matthews has nothing to disclose. Dr. Donnelly reports grants from AstraZeneca, from Boehringer-Ingelheim, outside the submitted work; . Dr. Simpson has nothing to disclose. Dr Baker has nothing to disclose. Dr. Fadai has nothing to disclose. Dr. Peterson reports personal fees from AstraZeneca, outside the submitted work; . Mr. Bengtsson reports personal fees from AstraZeneca, outside the submitted work; Dr. Barnes reports grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Teva, personal fees from Covis, during the conduct of the study; Dr. Russell reports grants from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi UK, personal fees from Glaxo-SmithKline, during the conduct of the study; . Dr. Bafadhel reports grants from AstraZeneca, personal fees from AstraZeneca, Chiesi, GSK, other from Albus Health, ProAxsis, outside the submitted work; . Ethics Approval Statement: The trial was sponsored by the University of Oxford, and was approved by the Fulham London Research Ethics Committee (20/HRA/2531) and the National Health Research Authority.The ethical approval number is 20/HRA/2531.

The article examines the question of the women religious mentorship in modern Iran. It is shown that Iranian theologians differed in their opinion whether a woman can be a religious mentor (marja): many of them supported it, others agreed to it only if she should mentor other women, and many others, including Ayatollah Khomeini, opposed it. Brief biographies of two most prominent female marjas are given: those of Nesrat Amin and Zahra Sefati. Both of them received a permission to interpret Islamic texts from distinguished Iranian ayatollahs. With theirinitiative and eagernessfor knowledge, they managed to succeed in Shiite theology and their works were highly regarded by Iranian ayatollahs. It is evident that their activities were closely linked to important events that happened in Iranian society during their lifetime: the Constitutional Revolution, anti-religious Shah regime, Islamic Revolution. Currently due to increase in the education and social activity among women, a need arose to officially allow women to become marja. Today, in Iran there works the Women Council on Islamic Law, what allows to expand the role of women in development of Islamic Law

Epidemic models have previously been employed to better understand the spread of internet content, such as individual viral videos. Motivated by geographical differences between viewing populations, as well as by multiple viral videos which are linked or related in some way, we propose a multi-group susceptible–exposed–infected–recovered–susceptible (SEIRS) delay differential equation epidemic model for the popularity evolution of viral videos. The model accounts for the multi-group environment via (in general, heterogeneous) networks of single-group SEIRS equations. Existence and stability conditions for disease-free and endemic equilibrium states are obtained, while numerical simulations demonstrate the emergence of non-symmetric endemic equilibrium states across the network — in the case of heterogeneous parameters. In order to demonstrate the effectiveness of our modeling approach, we compare solutions to our model with data obtained from coupled YouTube videos. Our results demonstrate that the inclusion of coupling between such videos allows for better agreement with data than considering each video in isolation. Such results suggest that the multi-group epidemic modeling approach including time delays and coupling between videos is a useful tool for understanding the dynamics of viral videos which are connected in some manner. While the proposed network SEIRS differential delay equation epidemic model was applied to viral video data, it may be applicable to a wide variety of internet content and, more generally, may be used to model information propagation within and between communities under the assumption of time delays in information propagation.

This study provides an overview of sustainable reusable load-bearing constructions as a contribution to the debate over whether building construction provides the building industry with the best and most environmentally friendly qualities. By contrasting their building-specific features, it demonstrates the benefits and drawbacks of particular structural elements and envelope solutions and ecological aspects using various system boundaries of life-cycle assessment (LCA). Following a careful consideration of ecological factors and sustainable circular economy criteria, a structural component that is sustainably optimized is defined. This component should be chosen based on external conditions. By selecting environmentally friendly building materials and proper connecting procedures that enable separability, resource-efficient and sustainable buildings can be achieved. Both the selection of load-bearing elements and the necessary insulating material have a significant impact on the ecological performance and reusability options of the components. The elements of homogeneity, separability, and pollutant-freeness play a significant influence in the reuse process, namely in terms of details and construction type in general, as well as the ways of reusing and recycling them. Sustainable solutions for load-bearing building components can be created by simultaneously investigating environmentally friendly building materials and the structure of the components. This paper illustrates how the natural resources can be used both optimally and sustainably. It presents a conceptual framework for scenario development of the LCA of load-bearing structures, their effect on the design and decision-making process. There is a potential of increasing total resource efficiency at the building level with a suitable combination of the material components employed at the component level. Because of this, the overall energy efficiency and its consequent ecological impacts are the main topics of this study.

Summary Background Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. Methods We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 400 μg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. Findings From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned—73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the usual care group and one (1%) of 69 participants in the budesonide group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0–50] vs 50% [15–71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference −0·12, 95% CI −0·21 to −0·02 [p=0·016]; FLUPro mean difference −0·10, 95% CI −0·21 to −0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. Interpretation Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. Funding National Institute for Health Research Biomedical Research Centre and AstraZeneca.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

BackgroundMultiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness.MethodsWe conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.Results146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care.ConclusionEarly administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.(Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca;ClinicalTrials.govnumber,NCT04416399)Research in contextEvidence before this studyThe majority of interventions studied for the COVID-19 pandemic are focused on hospitalised patients. Widely available and broadly relevant interventions for mild COVID-19 are urgently needed.Added value of this studyIn this open label randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19 illness, reduces the likelihood of requiring urgent care, emergency department consultation or hospitalisation. There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19 and a faster self-reported and questionnaire reported symptom resolution. There were fewer participants with persistent COVID-19 symptoms at 14 and 28 days after budesonide therapy compared to usual care.Implications of all the available evidenceThe STOIC trial potentially provides the first easily accessible effective intervention in early COVID-19. By assessing health care resource utilisation, the study provides an exciting option to help with the worldwide pressure on health care systems due to the COVID-19 pandemic. Data from this study also suggests a potentially effective treatment to prevent the long term morbidity from persistent COVID-19 symptoms.

We examine travelling wave solutions of the reaction–diffusion equation, ∂ t u = R ( u ) + ∂ x D ( u ) ∂ x u , with a Stefan-like condition at the edge of the moving front. With only a few assumptions on R(u) and D(u), a variety of new semi-infinite travelling waves arise in this reaction–diffusion Stefan model. While other reaction–diffusion models can admit semi-infinite travelling waves for a unique wavespeed, we show that semi-infinite travelling waves in the reaction–diffusion Stefan model exist over a range of wavespeeds. Furthermore, we determine the necessary conditions on R(u) and D(u) for which semi-infinite travelling waves exist for all wavespeeds. Using asymptotic analysis in various distinguished limits of the wavespeed, we obtain approximate solutions of these travelling waves, agreeing with numerical simulations with high accuracy.

While the pathological mechanisms in COVID-19 illness are still poorly understood, it is increasingly clear that high levels of pro-inflammatory mediators play a major role in clinical deterioration in patients with severe disease. Current evidence points to a hyperinflammatory state as the driver of respiratory compromise in severe COVID-19 disease, with a clinical trajectory resembling acute respiratory distress syndrome, but how this ‘runaway train’ inflammatory response emerges and is maintained is not known. Here, we present the first mathematical model of lung hyperinflammation due to SARS-CoV-2 infection. This model is based on a network of purported mechanistic and physiological pathways linking together five distinct biochemical species involved in the inflammatory response. Simulations of our model give rise to distinct qualitative classes of COVID-19 patients: (i) individuals who naturally clear the virus, (ii) asymptomatic carriers and (iii–v) individuals who develop a case of mild, moderate, or severe illness. These findings, supported by a comprehensive sensitivity analysis, point to potential therapeutic interventions to prevent the emergence of hyperinflammation. Specifically, we suggest that early intervention with a locally acting anti-inflammatory agent (such as inhaled corticosteroids) may effectively blockade the pathological hyperinflammatory reaction as it emerges.

The existence and uniqueness of the infectious steady-state, as well as a description of the global sensitivity analysis via eFAST.

We present a solid theoretical foundation for interpreting the origin of Allee effects by providing the missing link in understanding how local individual-based mechanisms translate to global population dynamics. Allee effects were originally proposed to describe population dynamics that cannot be explained by exponential and logistic growth models. However, standard methods often calibrate Allee effect models to match observed global population dynamics without providing any mechanistic insight. By introducing a stochastic individual-based model, with proliferation, death, and motility rates that depend on local density, we present a modelling framework that translates particular global Allee effects to specific individual-based mechanisms. Using data from ecology and cell biology, we unpack individual-level mechanisms implicit in an Allee effect model and provide simulation tools for others to repeat this analysis.

International audience; Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described.Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs.Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04−0.1, p =2 × 10−16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004−0.01, p = .026).Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents

In the last years several projects of medium and high-rise timber-based multi-story buildings have been proposed and developed. In most of the cases timber-concrete composite (TCC) floors play a significant role for the design of the structural slabs due to acoustic performance, fire protection and structural issues. Within several research projects and with the aim to optimize the structural and ecological characteristics of building components the Department of Structural Design and Timber Engineering (ITI) at the Vienna University of Technology (TU Wien) developed timber-steel hybrid beams that can be used independently or combined with concrete floors, proposing for this last case prefabricated and semi-prefabricated timber-steel-concrete ribbed elements that make the most of all this potential.In order to recognize the potential for future market implementation and to demonstrate the competiveness of the developed hybrid ribbed floor slabs, the economic feasibility and the ecological impact, structural elements were analyzed in several case studies. The environmental assessment shows the ecological advantages of the developed concepts and underlines the potential for further developments. This paper contains an introduction on the state-of-the-art floor solutions for timber-based multistory buildings, the fundamental ideas and design concepts behind the timber-steel and timber-steel-concrete proposals as well as a short review of the tests carried until now and results obtained.

While the processes underlying the roasting of a single coffee bean have been the focus of a number of recent studies, the more industrially relevant problem of roasting an array of coffee beans has not been well studied from a modeling standpoint. Starting with a microscale model for the heat and mass transfer processes within a single bean during roasting, we apply homogenization theory to upscale this model to an effective macroscale model for the roasting of an array of coffee beans. We then numerically simulate this effective model for two caricatures of roasting configurations which are of great importance to industrial scale coffee bean roasting: namely, drum roasters (where the beans are placed in a rotating drum) and fluidized bed roasters (where hot air is blown through the beans). The derivation of the homogenization problem has been carried out in a three-dimensional rectangular geometry. Simulations are presented both for simplified one-dimensional arrays of three-dimensional beans (as these are easier to visualize), as well as cross sections of full three-dimensional arrays of beans (for the sake of verification). We also verify our simulation results against experimental data from the literature. Among the findings is that increasing the air-to-bean volume fraction ratio decreases the drying time for the array of beans in a linear manner. We also find that, in the case of a fluidized bed, an increase in the hot air inflow velocity will decrease the drying time in a nonlinear manner, with diminishing returns observed beyond some point for large enough air inflow velocities.

Within several research projects and with the aim to optimize structural performance, energy efficiency and ecological characteristics of structural building components the Department of Structural Design and Timber Engineering (ITI) at the Vienna University of Technology (TU Wien) developed several wood-based composite systems, which combine timber products with other conventional building materials and components. As a representative example for these developments, this paper illustrates the results of the joint research project “Wood-based concrete: building construction with composite elements of wood-concrete compounds and timber (WooCon)”. The objective of the research project “WooCon” is to develop a multi-layer wall system composed of wood lightweight concrete (WLC), connected timber sections, textile reinforcement as well as glass layers on the exterior to gain and use advantages of each used material - lightweight, structural, thermal storage and insulation, ecological and economic benefits - to name the most important ones. In order to assess the structural physical properties of wood-based composite wall elements, in a first step measurements of the thermal properties with respect to thermal-insulating properties and thermal storage capacity are carried out. In following step, the results obtained are used further to simulate the thermodynamic and hygrothermal building behavior. The aim of the simulations is to investigate the effect of the wood-based composite wall elements to the annual heating demand as well as to the operative room temperature of a typical south-orientated living space.

Objective: White matter microstructure alterations have recently been associated with depressive episodes during adolescence, but it is unknown whether they predate depression. The authors investigated whether subthreshold depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome. Method: Adolescents with subthreshold depression (N=96) and healthy control subjects (N=336) drawn from a community-based cohort were compared using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followed up at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines spreading from the regions identified in the TBSS analysis and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. The authors searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold depression and depression at follow-up, and then explored the specificity of the findings. Results: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between subthreshold depression at baseline and depression at follow-up was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression. Conclusions: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex may denote a higher risk of transition to depression in adolescents.