Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.

Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

This corrects the article DOI: 10.1038/ni.3713.

Optimizing non-Newtonian fluids for impact protection of laminates.

Non-Newtonian fluids can be used for the protection of flexible laminates. Understanding the coupling between the flow of the protecting fluid and the deformation of the protected solids is necessary in order to optimize this functionality. We present a scaling analysis of the problem based on a single coupling variable, the effective width of a squeeze flow between flat rigid plates, and predict that impact protection for laminates is optimized by using shear-thinning, and not shear-thickening, fluids. The prediction is verified experimentally by measuring the velocity and pressure in impact experiments. Our scaling analysis should be generically applicable for non-Newtonian fluid-solid interactions in diverse applications.

Ductile-to-brittle transition and yielding in soft amorphous materials: perspectives and open questions.

Soft amorphous materials are viscoelastic solids ubiquitously found around us, from clays and cementitious pastes to emulsions and physical gels encountered in food or biomedical engineering. Under an external deformation, these materials undergo a noteworthy transition from a solid to a liquid state that reshapes the material microstructure. This yielding transition was the main theme of a workshop held from January 9 to 13, 2023 at the Lorentz Center in Leiden. The manuscript presented here offers a critical perspective on the subject, synthesizing insights from the various brainstorming sessions and informal discussions that unfolded during this week of vibrant exchange of ideas. The result of these exchanges takes the form of a series of open questions that represent outstanding experimental, numerical, and theoretical challenges to be tackled in the near future.

Evaluation of Upper Extremity Reachable Workspace in Children With Brachial Plexus Birth Injury.

PURPOSE: Brachial plexus birth injury (BPBI) results in upper extremity (UE) movement limitations. Current assessments of UE function used to inform clinical decision-making only evaluate a limited set of static postures and/or movements and have been criticized for being insensitive to certain meaningful differences in function. Reachable workspace provides a numeric and visual assessment of global UE movement ability by quantifying the regions in space that patients can reach with their hands, and it can be collected using real-time feedback to elicit a best-effort acquisition of function. This study evaluated the ability of a real-time feedback reachable workspace tool to assess UE movement in BPBI. METHODS: Twenty-two children with BPBI participated. Reachable workspace data were collected with three-dimensional motion capture using real-time visual feedback to measure UE reaching ability in all regions surrounding the body. All outer, far-from-body points reached by the hand were recorded and analyzed by region. A two-way, within-subjects analysis of variance was used to assess interlimb differences in percentage workspace reached and median reach distance for each of the six regions. RESULTS: The affected limb had significantly less percentage workspace reached than the unaffected limb for all six regions (mean interlimb differences by region, 5.7%-38.6%). The affected limb had significantly less median reach distance than the unaffected limb for all six regions (mean interlimb differences by region, 3.1%-36.8%). CONCLUSIONS: The workspace approach was capable of detecting UE movement impairments of the BPBI-affected limb. The reported deficits in workspace on the affected limb correspond to common movement impairments in BPBI, such as limitations in shoulder elevation, external rotation, extension, and elbow extension. CLINICAL RELEVANCE: The real-time feedback reachable workspace tool is sufficiently robust for assessing UE movement impairments in children with BPBI.

Impact of tendon transfer on scapulothoracic and glenohumeral motion in children with brachial plexus birth injuries.

BACKGROUND: Tendon transfers are often utilized to improve shoulder external rotation and abduction in children with brachial plexus birth injuries and are designed to improve glenohumeral (GH) joint motion. However, changes in scapulothoracic (ST) and glenohumeral (GH) joint function after tendon transfer are not well defined. The purpose of this study was to quantify changes in GH, ST, and humerothoracic (HT) joint function before and after tendon transfer, and we hypothesized that tendon transfers would reorient the arc of motion into more external rotation and abduction, but not increase GH motion. METHODS: Motion analysis was performed in 15 children (ages 3-16) before and after transfer of teres major and/or latissimus dorsi. Scapulothoracic, GH, and HT joint angles were measured in a neutral, resting position and each of the modified Mallet positions. Joint angular displacements from the neutral position and the total arc of internal-external rotation for each joint were also calculated. Relevant joint angles, joint angular displacements, and internal-external rotation arcs were compared using multivariate analyses of variance with repeated measures and univariate post-hoc analyses. RESULTS: Glenohumeral and HT external rotation were significantly increased in all positions postoperatively. The arc of GH internal-external rotation was unchanged, but oriented in more external rotation after surgery. Only 6 patients gained active external rotation. Glenohumeral and HT internal rotation were significantly decreased after surgery, but ST internal rotation was significantly increased. Two patients had loss of midline function. In the abduction position, GH elevation joint angles were unchanged, but ST and HT elevation increased. DISCUSSION: Only four patients gained active GH external rotation and maintained their internal rotation. Each of those patients underwent isolated tendon transfer without concomitant joint release. Seven patients maintained their preoperative internal rotation, which was attributed to increased ST internal rotation. The other half of patients lost internal rotation and gained external rotation through reorientation of the arc of rotation. Nine patients gained HT elevation, with three attributed to increased ST upward rotation, five attributed to a combination of increased ST upward rotation and increased GH elevation, and one attributed to increased GH abduction contracture. These findings challenge the dogma that teres major/latissimus dorsi tendon transfers augment GH motion and highlight the importance of ST function for outcome determination.

Working it out: Will the improved management of leaky bodies in the workplace create a dialogue between medical sociology and disability studies?

This article focuses on the workplace as a significant site of convergence between the disciplines of medical sociology and disability studies. As disability remains on the margins of sociological exploration and theorising relating to health and work, disabled workers remain on the margins of the workforce, subject to disproportionate rates of unemployment, under employment and workplace mistreatment. The article focuses on the experiences of people with 'leaky bodies', focussing specifically on employees who experience troubling menstruation and/or have gynaecological health conditions. It brings together data from three studies conducted between 2017 and 2020; interviews with disabled academics (n = 75), university staff with gynaecological health conditions (n = 23), and key stakeholders in universities (n = 36) (including university executives, line managers and human resources staff). These studies had separate, but linked foci, on the inaccessibility of workplaces, managing gynaecological health conditions at work and supporting disabled people at work respectively. Drawing on the Social Relational Model of disability and theories of embodiment, we explore the experiences and management of workers with leaky bodies in UK University workplaces. Data illustrates how workplace practices undermine embodied experiences of workers with 'leaky' bodies by maintaining workplaces which ignore their material reality. We highlight that addressing embodied needs alongside acknowledging disabled people as an oppressed political category represents a theoretical meeting point for disability studies and medical sociology.

Liver Transplantation Outcomes From Controlled Circulatory Death Donors: SCS vs in situ NRP vs ex situ NMP.

OBJECTIVE: To compare the outcomes of livers donated after circulatory death (DCD) and undergoing either in situ normothermic regional perfusion (NRP) or ex situ normothermic machine perfusion (NMP) with livers undergoing static cold storage (SCS). SUMMARY OF BACKGROUND DATA: DCD livers are associated with increased risk of primary nonfunction, poor function, and nonanastomotic strictures (NAS), leading to underutilization. METHODS: A single center, retrospective analysis of prospectively collected data on 233 DCD liver transplants performed using SCS, NRP, or NMP between January 2013 and October 2020. RESULTS: Ninety-seven SCS, 69 NRP, and 67 NMP DCD liver transplants were performed, with 6-month and 3-year transplant survival (graft survival non-censored for death) rates of 87%, 94%, 90%, and 76%, 90%, and 76%, respectively. NRP livers had a lower 6-month risk-adjusted Cox proportional hazard for transplant failure compared to SCS (hazard ratio 0.30, 95% Confidence Interval 0.08-1.05, P = 0.06). NRP and NMP livers had a risk-adjusted estimated reduction in the mean model for early allograft function score of 1.52 (P < 0.0001) and 1.19 (P < 0.001) respectively compared to SCS. Acute kidney injury was more common with SCS (55% vs 39% NRP vs 40% NMP; P = 0.08), with a lower risk-adjusted peak-to-baseline creatinine ratio in the NRP (P = 0.02). No NRP liver had clinically significant NAS in contrast to SCS (14%) and NMP (11%, P = 0.009), with lower risk-adjusted odds of overall NAS development compared to SCS (odds ratio = 0.2, 95%CI 0.06-0.72, P = 0.01). CONCLUSION: NRP and NMP were associated with better early liver function compared to SCS, whereas NRP was associated with superior preservation of the biliary system.

Scapulothoracic and Glenohumeral Contributions to Humerothoracic Kinematics in Single Versus Double Tendon Transfers in Patients With Brachial Plexus Birth Injury.

PURPOSE: Evidence suggests that patients with brachial plexus birth injury are more likely to retain midline function following a teres major tendon transfer without a concomitant latissimus dorsi transfer. Both procedures increase shoulder external rotation and abduction, but whether increased loss of midline frequency following double transfer is due to glenohumeral (GH) joint motion or scapulothoracic (ST) compensation is unknown. We hypothesized that double tendon transfers would exhibit greater GH external rotation than single tendon transfers, thus requiring greater ST rotation to internally rotate the shoulder, while GH and ST contributions to elevation remained equivalent between both groups. METHODS: Twenty-six postsurgical children with C5/C6 brachial plexus birth injuries participated in this study. Thirteen patients with single tendon transfers were matched with 13 with double tendon transfer. Coordinate systems of the thorax, scapula, and humerus were measured utilizing motion capture in 6 arm positions. Joint angles were calculated by the helical (ST) and modified globe method (GH and humerothoracic [HT]). Differences between groups were compared with repeated measures of multivariate analyses of variance for each position. Pending significant multivariate analyses of variance, univariate analyses of variance determined joint differences between transfer groups. RESULTS: Joint rotations from neutral were similar between groups in 5 of 6 tested positions, with double tendon transfers consistently demonstrating 15°-20˚ more internal rotation at the GH and HT joints. Still, only the internal rotation position showed statistically significant differences in GH and HT joint angles. The ST joint angles were similar in this position (45.2˚ and 48.5˚). CONCLUSIONS: The arc of motion for patients with double tendon transfer was more internally rotated than in patients with single tendon transfer at the GH and HT joints for all positions. However, both groups demonstrated little active rotation from neutral. Based on this data, teres major-only tendon transfers may not reduce the risk of loss of midline function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Comparison of Shoulder Motion Measurements by Visual Estimate, Goniometer and Motion Capture.

BACKGROUND: Brachial plexus birth injuries (BPBI) can result in lasting impairments of external rotation and cross-body adduction (CBA) that disrupt functional activities such as dressing, grooming, or throwing a ball. The purpose of this study was to compare the quantification of shoulder humerothoracic (HT) external rotation (ER), and glenohumeral (GH) CBA by 3 methods - physician visual estimate, goniometer measurement by an occupational therapist, and motion capture. METHODS: Twenty-six patients with BPBI (average age of 9.9±3.2 y) participated in this study. Mallet scores and visual estimates of passive HT ER and GH CBA were recorded by a physician. The passive measures were repeated by an occupational therapist using a goniometer while motion capture measures were simultaneously collected. Active HT ER was also measured by motion capture. The passive measures were compared with analyses of variance with repeated measures, intraclass correlations, and Bland-Altman plots. External rotation Mallet scores determined by motion capture and by the physician were compared. RESULTS: The measures of GH CBA were not statistically different and demonstrated good agreement, but substantial variation. For HT ER, all measures were significantly different and demonstrated poor agreement and substantial variation. When the joint angles measured by motion capture were used to determine the Mallet score, 79% of external rotation Mallet scores assigned by the physician were incorrectly categorized, with the physician always scoring the participant higher than predicted motion capture Mallet score. CONCLUSIONS: Both GH CBA and HT ER measures demonstrated substantial variability between measurement types, but only HT ER joint angles were significantly different. In addition, more than three-quarters of external rotation Mallet scores were misclassified by the physician. Motion capture measurements offer the benefit of less susceptibility to patients' compensatory and/or out-of-plane movements and should be considered for clinical assessment of shoulder range of motion in children with BPBI. If motion capture is unavailable, the use of a goniometer provides more accurate clinical measures of shoulder motion than visual estimates and care should be taken to minimize and account for compensatory movement strategies. LEVEL OF EVIDENCE: Level IV Case series.

Assessment of the relationship between Brachial Plexus Profile activity short form scores and modified Mallet scores.

INTRODUCTION: This study aims to assess the relationship between the modified Mallet classification and the Brachial Plexus Profile activity short form (BP-PRO activity SF). The therapist or surgeon classifies upper extremity movement for the modified Mallet classification, while the BP-PRO assesses parents' perceptions of difficulty performing activities. PURPOSE: To provide a deeper understanding of the relationship of functional and perceived outcome measurements. STUDY DESIGN: Prospective, correlational design. METHODS: Eighty children with brachial plexus birth injuries were evaluated using the modified Mallet classification, while parents simultaneously answered the BP-PRO activity SF questions. All patients had undergone one of three surgical interventions to improve shoulder function. The relationship between the two measures, patient injury levels, and surgical histories were assessed. RESULTS: The average modified Mallet scores and BP-PRO activity SF scores weakly correlated (r = 0.312, P = .005) and both measures differentiated between C5-6 and C5-7 injury levels (P = .03 and P = .02, respectively). Conversely, the modified Mallet scores could differentiate between the three surgical groups (F = 8.2, P < .001), while the BP-PRO activity SF could not (P = .54). CONCLUSION: The results suggest that these tools measure different aspects of patient outcomes. The Mallet classification may be more focused on shoulder motion than the BP-PRO activity SF. Additional questions that specifically require shoulder function could be incorporated into the BP-PRO activity SF to improve understanding of patient/parent perceptions of shoulder function for children with brachial plexus injuries. Clinicians should be aware of the strengths, weaknesses, and limitations of each outcome assessment tool for appropriate use and interpretation of results.

Trials & Tribulations of Liver Transplantation- are trials now prohibitive without surrogate endpoints?

During the past 5 decades, liver transplantation has moved from its pioneering days where success was measured in days to a point where it is viewed as a routine part of medical care. Despite this progress, there are still significant unmet needs and outstanding questions that need addressing in clinical trials to improve outcomes for patients. The traditional endpoint for trials in liver transplantation has been 1-year patient survival, but with rates now approaching 95%, this endpoint now poses a number of significant financial and logistical barriers to conducting trials because of the large numbers of participants required to demonstrate only an incremental improvement. Here, we suggest the following solutions to this challenge: adoption of validated surrogate endpoints; bigger and better collaborative multiarm, multiphase studies; recognition by funders and institutions that work on larger collaborative research projects is potentially more important than smaller, self-led bodies of work; ringfenced areas of research within trial frameworks where individuals can take a lead; and fair funding structures using both industry and public sector money across national and international borders.

Characterising shear-induced dynamics in flowing complex fluids using differential dynamic microscopy.

Microscopic dynamics reveal the origin of the bulk rheological response in complex fluids. In model systems particle motion can be tracked, but for industrially relevant samples this is often impossible. Here we adapt differential dynamic microscopy (DDM) to study flowing highly-concentrated samples without particle resolution. By combining an investigation of oscillatory flow, using a novel "echo-DDM" analysis, and steady shear, through flow-DDM, we characterise the yielding of a silicone oil emulsion on both the microscopic and bulk level. Through measuring the rate of shear-induced droplet rearrangements and the flow velocity, the transition from a solid-like to liquid-like state is shown to occur in two steps: with droplet mobilisation marking the limit of linear visco-elasticity, followed by the development of shear localisation and macroscopic yielding. Using this suite of techniques, such insight could be developed for a wide variety of challenging complex fluids.

Particle sizing for flowing colloidal suspensions using flow-differential dynamic microscopy.

Particle size is a key variable in understanding the behaviour of the particulate products that underpin much of our modern lives. Typically obtained from suspensions at rest, measuring the particle size under flowing conditions would enable advances for in-line testing during manufacture and high-throughput testing during development. However, samples are often turbid, multiply scattering light and preventing the direct use of common sizing techniques. Differential dynamic microscopy (DDM) is a powerful technique for analysing video microscopy of such samples, measuring diffusion and hence particle size without the need to resolve individual particles while free of substantial user input. However, when applying DDM to a flowing sample, diffusive dynamics are rapidly dominated by flow effects, preventing particle sizing. Here, we develop "flow-DDM", a novel analysis scheme that combines optimised imaging conditions, a drift-velocity correction and modelling of the impact of flow. Flow-DDM allows a decoupling of flow from diffusive motion that facilitates successful particle size measurements at flow speeds an order of magnitude higher than for DDM. We demonstrate the generality of the technique by applying flow-DDM to two separate microscopy methods and flow geometries.

Pilot study of a noninvasive real-time optical backscatter probe in liver transplantation.

Transplantation of severely steatotic donor livers is associated with early allograft dysfunction and poorer graft survival. Histology remains the gold standard diagnostic of donor steatosis despite the lack of consensus definition and its subjective nature. In this prospective observational study of liver transplant patients, we demonstrate the feasibility of using a handheld optical backscatter probe to assess the degree of hepatic steatosis and correlate the backscatter readings with clinical outcomes. The probe is placed on the surface of the liver and emits red and near infrared light from the tip of the device and measures the amount of backscatter of light from liver tissue via two photodiodes. Measurement of optical backscatter (Mantel-Cox P < 0.0001) and histopathological scoring of macrovesicular steatosis (Mantel-Cox P = 0.046) were predictive of 5-year graft survival. Recipients with early allograft dysfunction defined according to both Olthoff (P = 0.0067) and MEAF score (P = 0.0097) had significantly higher backscatter levels from the donor organ. Backscatter was predictive of graft loss (AUC 0.75, P = 0.0045). This study demonstrates the feasibility of real-time measurement of optical backscatter in donor livers. Early results indicate readings correlate with steatosis and may give insight to graft outcomes such as early allograft dysfunction and graft loss.

Effect of Glenohumeral Reduction Type Combined With Tendon Transfer for Brachial Plexus Injury on Objective, Functional, and Patient-Reported Outcomes.

PURPOSE: Glenohumeral (GH) joint reductions are frequently performed during tendon transfer surgery for brachial plexus birth injuries (BPBI); however, the effect of reduction method (none required, closed, surgical) has not been assessed. This study compared objective, functional, and patient-reported outcomes between children who underwent a tendon transfer and (1) did not require GH reduction, (2) required concomitant closed GH reduction, or (3) required concomitant surgical GH reduction. METHODS: Fifty-four children with BPBI who previously underwent teres major and/or latissimus dorsi transfer with or without concomitant GH reduction participated. Joint reduction method was classified as none required (n = 21), closed (n = 9), or surgical (n = 24). Motion capture was collected in a neutral position, abduction, external rotation, and internal rotation. Glenohumeral joint angles and displacements were calculated. Joint angular displacements represented the differences between the joint angles in each terminal position and the joint angles of the arm at rest in the neutral position. A hand surgeon determined modified Mallet scores. Participants' parents completed the Brachial Plexus Profile Activity Short Form (BP-PRO-SF) to assess physical activity performance. RESULTS: The no-reduction group had significantly less GH elevation than the surgical-reduction group for all positions and significantly less GH elevation than the closed-reduction group for the neutral, external rotation, and internal rotation positions. There were no differences in GH rotation angles. Glenohumeral joint displacements from neutral and modified Mallet scores were similar. The no-reduction group demonstrated significantly greater BP-PRO-SF scores than the surgical-reduction group. CONCLUSIONS: Patients who underwent a closed or surgical GH joint reduction consistently displayed more GH elevation. Clinically, this corresponds to an abduction contracture. Whereas increased abduction contracture provided a benefit of greater overhead motion, modified Mallet scores were similar between groups. The surgical-reduction group demonstrated lower BP-PRO-SF outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Model for early allograft function is predictive of early graft loss in donation after circulatory death liver transplantation.

Donation after circulatory death (DCD) liver transplantation is associated with higher rates of graft loss. In this paper, we explored whether the Model for Early Allograft Function (MEAF) predicted outcome in DCD liver transplantation. We performed a retrospective analysis of prospectively collected data from all adult DCD (Maastricht 3) livers transplanted in Cambridge and Edinburgh between 1 January 2011 and 30 June 2017, excluding those undergoing any form of machine perfusion. 187 DCD liver transplants were performed during the study period. DCD liver transplants with a lower MEAF score had a significantly better survival compared to those with a high MEAF score (Mantel-Cox P < .0001); this was largely due to early graft loss. Beyond 28 days post-transplant, there were no significant long-term graft or patient survival differences irrespective of the grade of MEAF (Mantel-Cox P = .64 and P = .43, respectively). The MEAF score correlated with the length of ICU (P = .0011) and hospital stay (P = .0007), but did not predict the requirement for retransplantation for ischemic cholangiopathy (P = .37) or readmission (P = .74). In this study, a high MEAF score predicted early graft loss, but not the subsequent need for re-transplantation or late graft failure as a result of intrahepatic ischemic bile duct pathology.

Impact of Psychiatric Comorbidities on Health Care Costs Among Patients With Cancer.

BACKGROUND: Psychiatric disorders are common in cancer patients and impact outcomes. Impact on cancer care cost needs study to develop business case for psychosocial interventions. OBJECTIVE: To evaluate the impact of preexisting psychiatric comorbidities on total cost of care during 6 months after cancer diagnosis. METHODS: This retrospective cohort study examined patients diagnosed with cancer between January 1, 2009, and December 31, 2014, at one National Cancer Institute-designated cancer center. Patients who received all cancer treatment at the study site (6598 of 11,035 patients) were included. Patients were divided into 2 groups, with or without psychiatric comorbidity, based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Total costs of care during the first 6 months of treatment were based on standardized costs adjusted to 2014 dollars, determined by assigning Medicare reimbursement rates to professional billed services and applying appropriate cost-to-charge ratios. Quantile regression models with covariate adjustments were developed to assess the effect of psychiatric comorbidity across the distribution of costs. RESULTS: Six hundred ninety-eight (10.6%) of 6598 eligible patients had at least one psychiatric comorbidity. These patients had more nonpsychiatric Elixhauser comorbidities (mean 4 vs. 3). Unadjusted total cancer care costs were higher for patients with psychiatric comorbidity (mean [standard deviation]: $51,798 [$74,549] vs. $32,186 [$45,240]; median [quartiles]: $23,871 [$10,705-$57,338] vs. $19,073 [$8120-$38,230]). Quantile regression models demonstrated that psychiatric comorbidity had significant incremental effects at higher levels of cost: 75th percentile $8629 (95% confidence interval: $3617-13,642) and 90th percentile $42,586 (95% confidence interval: $25,843-59,330). CONCLUSIONS: Psychiatric comorbidities are associated with increased total cancer costs, especially in patients with very high cancer care costs, representing an opportunity to develop mitigation strategies.

Exome resequencing and GWAS for growth, ecophysiology, and chemical and metabolomic composition of wood of Populus trichocarpa.

BACKGROUND: Populus trichocarpa is an important forest tree species for the generation of lignocellulosic ethanol. Understanding the genomic basis of biomass production and chemical composition of wood is fundamental in supporting genetic improvement programs. Considerable variation has been observed in this species for complex traits related to growth, phenology, ecophysiology and wood chemistry. Those traits are influenced by both polygenic control and environmental effects, and their genome architecture and regulation are only partially understood. Genome wide association studies (GWAS) represent an approach to advance that aim using thousands of single nucleotide polymorphisms (SNPs). Genotyping using exome capture methodologies represent an efficient approach to identify specific functional regions of genomes underlying phenotypic variation. RESULTS: We identified 813 K SNPs, which were utilized for genotyping 461 P. trichocarpa clones, representing 101 provenances collected from Oregon and Washington, and established in California. A GWAS performed on 20 traits, considering single SNP-marker tests identified a variable number of significant SNPs (p-value < 6.1479E-8) in association with diameter, height, leaf carbon and nitrogen contents, and δ15N. The number of significant SNPs ranged from 2 to 220 per trait. Additionally, multiple-marker analyses by sliding-windows tests detected between 6 and 192 significant windows for the analyzed traits. The significant SNPs resided within genes that encode proteins belonging to different functional classes as such protein synthesis, energy/metabolism and DNA/RNA metabolism, among others. CONCLUSIONS: SNP-markers within genes associated with traits of importance for biomass production were detected. They contribute to characterize the genomic architecture of P. trichocarpa biomass required to support the development and application of marker breeding technologies.