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Background: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long‐term relief. Therefore, we investigated a novel self‐assembling tissue‐engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. Objectives: Examine the maturation of dynamic self‐regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. Materials and Methods: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin‐O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300–500 μm diameter and 1.2–1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser‐ablated lesion (experimental) and an empty laser‐ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. Results: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin‐O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. Conclusion: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair. [ABSTRACT FROM AUTHOR]

Vascularized composite allotransplantations are complex procedures with substantial functional impact on patients. Extended preservation of VCAs is of major importance in advancing this field. It would result in improved donor-recipient matching as well as the potential for ex vivo manipulation with gene and cell therapies. Moreover, it would make logistically feasible immune tolerance induction protocols through mixed chimerism. Supercooling techniques have shown promising results in multi-day liver preservation. It consists of reaching sub-zero temperatures while preventing ice formation within the graft by using various cryoprotective agents. By drastically decreasing the cell metabolism and need for oxygen and nutrients, supercooling allows extended preservation and recovery with lower ischemia–reperfusion injuries. This study is the first to demonstrate the supercooling of a large animal model of VCA. Porcine hindlimbs underwent 48 h of preservation at − 5 °C followed by recovery and normothermic machine perfusion assessment, with no issues in ice formation and favorable levels of injury markers. Our findings provide valuable preliminary results, suggesting a promising future for extended VCA preservation. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated a novel strategy for improving regenerative cartilage outcomes. It combines fractional laser treatment with the implantation of neocartilage generated from autologous dynamic Self-Regenerating Cartilage (dSRC). Methods: dSRC was generated in vitro from harvested autologous swine chondrocytes. Culture was performed for 2, 4, 8, 10, and 12 weeks to study matrix maturation. Matrix formation and implant integration were also studied in vitro in swine cartilage discs using dSRC or cultured chondrocytes injected into CO2 laser-ablated or mechanically punched holes. Cartilage discs were cultured for up to 8 weeks, harvested, and evaluated histologically and immunohistochemically. Results: The dSRC matrix was injectable by week 2, and matrices grew larger and more solid with time, generating a contiguous neocartilage matrix by week 8. Hypercellular density in dSRC at week 2 decreased over time and approached that of native cartilage by week 8. All dSRC groups exhibited high glycosaminoglycan (GAG) production, and immunohistochemical staining confirmed that the matrix was typical of normal hyaline cartilage, being rich in collagen type II. After 8 weeks in cartilage lesions in vitro, dSRC constructs generated a contiguous cartilage matrix, while isolated cultured chondrocytes exhibited only a sparse pericellular matrix. dSRC-treated lesions exhibited high GAG production compared to those treated with isolated chondrocytes. Conclusions: Isolated dSRC exhibits hyaline cartilage formation, matures over time, and generates contiguous articular cartilage matrix in fractional laser-created microenvironments in vitro, being well integrated with native cartilage. [ABSTRACT FROM AUTHOR]

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in theworld of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS. [ABSTRACT FROM AUTHOR]

Vascularized composite allografts (VCA) face ischemic challenges due to their limited availability. Reperfusion following ischemia triggers oxidative stress and immune reactions, and scavenger molecules could mitigate ischemia–reperfusion injuries and, therefore, immune rejection. We compared two scavengers in a myocutaneous flap VCA model. In total, 18 myocutaneous flap transplants were performed in Major histocompatibility complex (MHC)-defined miniature swine. In the MATCH group (n = 9), donors and recipients had minor antigen mismatch, while the animals were fully mismatched in the MISMATCH group (n = 9). Grafts were pretreated with saline, sodium iodide (NaI), or hydrogen sulfide (H2S), stored at 4 °C for 3 h, and then transplanted. Flaps were monitored until clinical rejection without immunosuppression. In the MATCH group, flap survival did not significantly differ between the saline and hydrogen sulfide treatments (p = 0.483) but was reduced with the sodium iodide treatment (p = 0.007). In the MISMATCH group, survival was similar between the saline and hydrogen sulfide treatments (p = 0.483) but decreased with the sodium iodide treatment (p = 0.007). Rhabdomyolysis markers showed lower but non-significant levels in the experimental subgroups for both the MATCH and MISMATCH animals. This study provides insightful data for the field of antioxidant-based approaches in VCA and transplantation. [ABSTRACT FROM AUTHOR]

Reconstructive techniques to repair severe tissue defects include the use of autologous fasciocutaneous flaps, which may be limited due to donor site availability or lead to complications such as donor site morbidity. A number of synthetic or natural dermal substitutes are in use clinically, but none have the architectural complexity needed to reconstruct deep tissue defects. The perfusion decellularization of fasciocutaneous flaps is an emerging technique that yields a scaffold with the necessary composition and vascular microarchitecture and serves as an alternative to autologous flaps. In this study, we show the perfusion decellularization of porcine fasciocutaneous flaps using sodium dodecyl sulfate (SDS) at three different concentrations, and identify that 0.2% SDS results in a decellularized flap that is efficiently cleared of its cellular material at 86%, has maintained its collagen and glycosaminoglycan content, and preserved its microvasculature architecture. We further demonstrate that the decellularized graft has the porous structure and growth factors that would facilitate repopulation with cells. Finally, we show the biocompatibility of the decellularized flap using human dermal fibroblasts, with cells migrating as deep as 150 µm into the tissue over a 7-day culture period. Overall, our results demonstrate the promise of decellularized porcine flaps as an interesting alternative for reconstructing complex soft tissue defects, circumventing the limitations of autologous skin flaps. [ABSTRACT FROM AUTHOR]

Background Photochemical tissue bonding (PTB) is a technique for peripheral nerve repair in which a collagenous membrane is bonded around approximated nerve ends. Studies using PTB with cryopreserved human amnion have shown promising results in a rat sciatic nerve transection model including a more rapid and complete return of function, larger axon size, and thicker myelination than suture repair. Commercial collagen membranes, such as dehydrated amnion allograft, are readily available, offer ease of storage, and have no risk of disease transmission or tissue rejection. However, the biomechanical properties of these membranes using PTB are currently unknown in comparison to PTB of cryopreserved human amnion and suture neurorrhaphy. Methods Rat sciatic nerves (n = 10 per group) were transected and repaired using either suture neurorrhaphy or PTB with one of the following membranes: cryopreserved human amnion, monolayer human amnion allograft (crosslinked and noncrosslinked), trilayer human amnion/chorion allograft (crosslinked and noncrosslinked), or swine submucosa. Repaired nerves were subjected to mechanical testing. Results During ultimate stress testing, the repair groups that withstood the greatest strain increases were suture neurorrhaphy (69 ± 14%), PTB with crosslinked trilayer amnion (52 ± 10%), and PTB with cryopreserved human amnion (46 ± 20%), although the differences between these groups were not statistically significant. Neurorrhaphy repairs had a maximum load (0.98 ± 0.30 N) significantly greater than all other repair groups except for noncrosslinked trilayer amnion (0.51 ± 0.27 N). During fatigue testing, all samples repaired with suture, or PTBs with either crosslinked or noncrosslinked trilayer amnion were able to withstand strain increases of at least 50%. Conclusion PTB repairs with commercial noncrosslinked amnion allograft membranes can withstand physiological strain and have comparable performance to repairs with human amnion, which has demonstrated efficacy in vivo. These results indicate the need for further testing of these membranes using in vivo animal model repairs. [ABSTRACT FROM AUTHOR]

The number of incidents worldwide where pile tip damage has occurred during driving has accelerated following the growth of the offshore wind sector, and the expansion into areas with increased risk of embedded boulders or partially weathered soft rocks. The process involving pile–boulder–soil contact can be simulated with advanced three-dimensional (3D) large-deformation dynamic coupled Eulerian–Lagrangian (CEL) finite-element (FE) analysis. However, analyses of this nature are highly time-consuming and computationally expensive. The objective of the paper is to develop a generic framework whereby the potential for denting by a boulder can be assessed a priori. The study encompasses four main components to determine the magnitude of force necessary to create plastic damage of the pile tip and what combination of boulders and soil might generate such reactions during pile installation: (a) a parametric 3D FE structural denting study; (b) a parametric boulder–soil 3D CEL study, where prescribed displacements were applied to the surface of boulders embedded in sand; (c) a range of pile–boulder–soil 3D CEL analyses where a deformable pile and different boulder–soil combinations were simulated; and (d) centrifuge model tests involving tip damage from boulders. Simple relationships and charts have been established from the numerical studies and validated from experimental work. [ABSTRACT FROM AUTHOR]

Background: In the last decade, tissue‐engineering strategies for regenerating the temporomandibular joint (TMJ) have been investigated. This may be a promising strategy for the minimally invasive restoration of joint integrity. Objectives: To evaluate whether dental pulp stem cells (DPSCs) loaded in a light‐occured hydrogel made of gelatin methacryloyl (GelMA) enhance the regeneration of osteochondral defects in the rabbit TMJ. Materials and Methods: Defects were filled with GelMA alone (control group; n = 4) or filled with GelMA loaded with rabbit DPSCs (experimental group; n = 4), In one group, the TMJ capsule was opened without creating a defect (sham group; n = 2). The following micro‐CT parameters were analysed: bone volume to total volume ratio (BV/TV%) and bone mineral density (BMD). Histological evaluation was performed to assess cartilage regeneration features. A semi‐quantitative scoring system was also used to evaluate the defects. Results: All groups had no statistical difference regarding the micro‐CT parameters. The highest mean healing score was found for the experimental group. After 4 weeks, there were no signs of hydrogel in either group or no signs of inflammation in the adjacent tissues. The tissue formed in the defect was dense fibrous connective tissue. Conclusion: Adding DPSCs to GelMA did not provide a regenerative enhancement in TMJ osteochondral defects. This resulted in similar micro‐CT parameters after 4 weeks of healing, with improved signs of subchondral bone regeneration but no cartilage regeneration. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections occur in about 2% of patients who undergo primary total joint arthroplasty, a procedure performed over 1 million times in the United States. The gold standard of treatment is a two‐stage revision. This study aimed to establish a two‐stage procedure in a preclinical small animal model (rat) to test and compare the efficacy of an antibiotic‐eluting material in managing infection. Joint replacement was simulated by transchondylarly implanting a polyethylene (PE) plug into the distal femur and a titanium screw in the proximal tibia. Methicillin‐sensitive Staphylococcus aureus (MSSA) 108 CFU/mL was injected into the tibial canal and the joint space before wound closure. The control groups were killed on postoperative day (POD) 18 (n = 12) and on POD 42 (n = 4) to assess both early and later‐stage outcomes in the control group. The test group underwent revision surgery on POD 18 for treatment using gentamicin‐eluting polyethylene (GPE, n = 4) and was observed until POD 42 to evaluate the efficacy of treatment. Our results showed that the bone loss for the treatment group receiving GPE was significantly less than that of the control (p < 0.05), which was supported by the histology images and an AI‐tool assisted infection rate evaluation. Gait metrics duty factor imbalance and hindlimb temporal symmetry were significantly different between the treatment and control groups on Day 42. This animal model was feasible for evaluating treatments for peri‐prosthetic joint infections (PJI) with a revision surgery and specifically that revision surgery and local antibiotic treatment largely hindered the peri‐prosthetic bone loss. Statement of clinical significance: This revision model of peri‐prosthetic infection has the potential of comparatively evaluating prophylaxis and treatment strategies and devices. Antibiotic‐eluting UHMWPE is devised as at tool in treating PJI while providing weight bearing and joint space preservation. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods: We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results: The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions: These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels. [ABSTRACT FROM AUTHOR]

The touchdown zones of steel catenary risers and lazy wave risers are fatigue hotspots, where the risers interact continuously with the seabed due to hydrodynamic loading exerted on the host vessel. The whole-life interactions can range from small-amplitude daily motion cycles to motions that involve large-amplitude cyclic interaction with the seabed during storm events. A key design challenge that affects the fatigue life of these risers is the accurate modelling of the evolution of the riser–soil stiffness, throughout the whole life of the riser and for different soil conditions, including overconsolidated conditions, which may occur due to the geological history, ageing or biochemical processes of the sediments. This paper describes centrifuge model pipe tests simulating whole-life riser–soil interaction in normally consolidated and uniform overconsolidated clay samples, under successive sequences of cyclic motions. Results confirm that the whole-life soil stiffness evolution depends strongly on cyclic amplitudes, with reconsolidation-induced soil stiffness recovery after heavy remoulding, and is also influenced by the soil overconsolidation ratio, with a reduced tendency for soil hardening at higher soil overconsolidation ratios. This study provides insights into the relevant cyclic soil stiffness to consider when assessing the whole-life design of risers interacting with overconsolidated seabed sediments. [ABSTRACT FROM AUTHOR]

Autonomization is a physiological process allowing a flap to develop neo-vascularization from the reconstructed wound bed. This phenomenon has been used since the early application of flap surgeries but still remains poorly understood. Reconstructive strategies have greatly evolved since, and fasciocutaneous flaps have progressively replaced muscle-based reconstructions, ensuring better functional outcomes with great reliability. However, plastic surgeons still encounter challenges in complex cases where conventional flap reconstruction reaches its limitations. Furthermore, emerging bioengineering applications, such as decellularized scaffolds allowing a complex extracellular matrix to be repopulated with autologous cells, also face the complexity of revascularization. The objective of this article is to gather evidence of autonomization phenomena. A systematic review of flap autonomization is then performed to document the minimum delay allowing this process. Finally, past and potential applications in bio- and tissue-engineering approaches are discussed, highlighting the potential for in vivo revascularization of acellular scaffolds. [ABSTRACT FROM AUTHOR]

Machine perfusion has developed rapidly since its first use in solid organ transplantation. Likewise, reconstructive surgery has kept pace, and ex vivo perfusion appears as a new trend in vascularized composite allotransplants preservation. In autologous reconstruction, fasciocutaneous flaps are now the gold standard due to their low morbidity (muscle sparing) and favorable functional and cosmetic results. However, failures still occasionally arise due to difficulties encountered with the vessels during free flap transfer. The development of machine perfusion procedures would make it possible to temporarily substitute or even avoid microsurgical anastomoses in certain complex cases. We performed oxygenated acellular sub-normothermic perfusions of fasciocutaneous flaps for 24 and 48 h in a porcine model and compared continuous and intermittent perfusion regimens. The monitored metrics included vascular resistance, edema, arteriovenous oxygen gas differentials, and metabolic parameters. A final histological assessment was performed. Porcine flaps which underwent successful oxygenated perfusion showed minimal or no signs of cell necrosis at the end of the perfusion. Intermittent perfusion allowed overall better results to be obtained at 24 h and extended perfusion duration. This work provides a strong foundation for further research and could lead to new and reliable reconstructive techniques. [ABSTRACT FROM AUTHOR]

Pile drivability predictions require information on the pile geometry, impact hammer, and the soil resistance to driving (SRD). Current SRD prediction methods are based on databases of long slender piles from the oil and gas industry and new, robust, and adaptable methods are required to predict SRD for current offshore pile geometries. This paper describes an optimization framework to update uncertain model parameters in existing axial static design methods to calibrate SRD. The approach is demonstrated using a case study from a German offshore wind site. The optimization process is undertaken using a robust Bayesian approach to dynamically update uncertain variables during driving to improve simulations. The existing method is shown to perform well for piles with geometries that reflect the underlying database such that only minimal optimization is required. For larger diameter piles, relative to the prior best estimate, optimized results are shown to provide significant improvements in the mean calculations and associated variance of pile drivability as more data is acquired. The optimized parameters can be used to predict SRD for similar piles in analogous ground conditions. The demonstrated framework is adaptable and can be used to develop site-specific calibrations and advance new SRD methods where large pile driving data sets are available. [ABSTRACT FROM AUTHOR]

Background: Rodent models are commonly employed to validate preclinical disease models through the evaluation of postoperative behavior and allodynia. Our study investigates the dynamic interplay between pain and functional recovery in the context of traumatic osteotomy and surgical repair. Specifically, we established a rat model of tibial osteotomy, followed by internal fixation using a 5-hole Y-plate with 4 screws, to explore the hypothesis that histological bone healing is closely associated with functional recovery. Objective: Our primary objective was to assess the correlation between bone healing and functional outcomes in a rat model of tibial osteotomy and plate fixation. Methods: Seventeen male Sprague–Dawley rats underwent a metaphyseal transverse osteotomy of the proximal tibia, simulating a fracture-like injury. The resultant bone defect was meticulously repaired by realigning and stabilizing the bone surfaces with the Y-plate. To comprehensively assess recovery and healing, we performed quantitative and qualitative evaluations at 2, 4, 6, and 8 weeks post-surgery. Evaluation methods included micro-CT imaging, X-ray analysis, and histological examination to monitor bone defect healing. Concurrently, we employed video recording and gait analysis to evaluate functional recovery, encompassing parameters such as temporal symmetry, hindlimb duty factor imbalance, phase dispersion, and toe spread. Results: Our findings revealed complete healing of the bone defect at 8 weeks, as confirmed by micro-CT and histological assessments. Specifically, micro-CT data showed a decline in fracture volume over time, indicating progressive healing. Histological examination demonstrated the formation of new trabecular bone and the resolution of inflammation. Importantly, specific gait analysis parameters exhibited longitudinal changes consistent with bone healing. Hindlimb duty factor imbalance, hindlimb temporal symmetry, and phase dispersion correlated strongly with the healing process, emphasizing the direct link between bone healing and functional outcomes. Conclusions: The establishment of this tibia osteotomy model underscores the association between bone healing and functional outcomes, emphasizing the feasibility of monitoring postoperative recovery using endpoint measurements. Our overarching objective is to employ this model for assessing the local efficacy of drug delivery devices in ameliorating post-surgical pain and enhancing functional recovery. [ABSTRACT FROM AUTHOR]

Design codes vary in their recommendations for the end-bearing response for bored piles founded in sand, both for the ultimate design value and the response at small settlements. The ultimate end-bearing resistance may be expressed either in terms of bearing factors Nq relative to the in situ vertical effective stress, with the Nq value varying with the friction angle of the sand, or as a factor applied to in situ test data, such as the standard penetration test blow count or the tip resistance qc. Numerical studies have led to proposed ratios of design end-bearing pressure to qc at specific settlement ratios, such as 5% and 10% of the pile diameter. The work presented here used numerical analysis to evaluate the full pile base response from initial stiffness to ultimate end-bearing resistance at a settlement ratio of 10% of the pile diameter. The resulting base responses are suitable for implementation in beam column analyses and have been validated by comparison with published design guidelines and with data from a full-scale instrumented pile load test. [ABSTRACT FROM AUTHOR]

Background For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. Methods Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. Results Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group (p = 0.01613). Conclusion To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation. [ABSTRACT FROM AUTHOR]

A number of incidents of pile tip damage and extrusion buckling have been reported within the offshore industry, generally arising during driving of relatively thin-walled tubular pile foundations through hard layers or potentially heterogeneous sediments. The issue has become of particular concern with modern trends toward larger diameter piles, with higher ratios of diameter to wall thickness, for monopile or jacket foundations of offshore wind turbines. The paucity of good-quality data available in the public domain about this kind of failure has impaired the development of simple design guidelines for industry to address the issue. The paper presents results from a series of centrifuge model tests where pile tip damage and extrusion buckling were observed during driving of either (1) undamaged cylindrical piles into a sand bed containing a layer of different sizes of boulders, or (2) predented piles into medium dense homogeneous sand. Following a previously reported pilot study, a new and higher energy model pile-driving hammer was designed to permit driving through the hard layers and allow pile embedment by up to five diameters. Two test beds were prepared, one of which contained boulder layers of different sizes either near the surface or at a depth of about one pile diameter, into which piles of two different diameter to wall thickness ratios were driven. The test series led to observations of pile tip damage that ranged from abrupt tip crumpling to gradual extrusion buckling. For 2 of the 22 piles installed, dent growth during installation was detected by optical fiber sensors attached to the piles. For the uninstrumented piles, damage was deduced from the trends in blow counts during installation, with later confirmation from detailed visual inspections and laser scanning, and also from careful layer by layer excavation of each sample. The high-quality database generated from the model tests forms a valuable resource for further study and validation of advanced numerical models to simulate pile tip damage and for calibration of simple guidelines for practical design. [ABSTRACT FROM AUTHOR]

Background. There have been few advances in technique since vascular anastomosis was performed with silk suture on a curved needle in 1902. This technique results in disruption of the endothelium with exposed intraluminal suture, both of which may lead to thrombocyte aggregation, intimal hyperplasia, and vascular stenosis. A variety of alternative techniques have been explored, with limited success. Photochemical tissue bonding (PTB) is a light-activated methodology of rapidly cross-linking tissue interfaces at the molecular level. Herein, we describe a new technique for anastomosis of venous interposition graft in an ovine model of femoral artery bypass utilizing PTB. Methods. Polypay specific pathogen free sheep (n = 5; 40-45 kg) underwent femoral artery bypass utilizing saphenous vein. The femoral artery was transected and reversed saphenous vein was implanted as an interposition graft. The proximal anastomosis was created as a vein-over-artery cuff utilizing PTB, and the distal anastomosis was created with standard interrupted 8-0 polypropylene suture. Four weeks post-index operation, femoral angiogram was performed to evaluate patency, tortuosity, and luminal diameter. All bypass grafts were harvested and longitudinal and transverse histological sections from the proximal anastomosis were analyzed. Results. The PTB anastomoses (n = 5) were immediately watertight and patent. All animals survived the 28-day study duration. Angiography revealed patent grafts with no aneurysm or stenosis (n = 5). Histologic examination revealed integration of the venous endothelium with the arterial adventitia. Conclusion. Photochemical tissue bonding creates an immediate strong, watertight vascular anastomosis that can withstand physiologic arterial pressure and remains patent at 28 days without the need for intraluminal suture. [ABSTRACT FROM AUTHOR]

The performance of plate anchors in sand, relative to clay, is not well understood, particularly for the more realistic case of an inclined load. This paper investigates the effect of load inclination on horizontal plate anchors in sand through centrifuge tests and numerical finite-element simulations. The centrifuge tests were performed on rectangular plate anchors in loose and dense sand, at shallow embedment depths with four different load inclinations. The experiments showed that the anchor capacity of horizontal plates increased progressively as the load inclination became progressively more horizontal, with anchor capacity under pure horizontal loading being approximately 1·8 times higher than that under pure vertical loading. These experimental observations were also replicated in finite-element simulations using a bounding surface plasticity model. Investigation of the underlying failure mechanisms and stress paths showed that the slip planes become longer and the mobilised lateral stresses increase as the load inclination becomes increasingly horizontal, which leads to higher anchor capacities. Finally, the anchor resistance factors from the numerical analyses were decoupled into vertical and horizontal components and represented as interaction diagrams, providing a basis for performing hand calculations of anchor capacity for a given embedment depth, load inclination and relative density. [ABSTRACT FROM AUTHOR]

This paper examines the effect of consolidation on a shallowly embedded horizontal plate anchor in medium dense and dense sand using centrifuge tests, where the loading rate was varied over four orders of magnitude. The experimental results show a 4·8 to 5·5 times increase in anchor capacity as the consolidation condition changes from drained to undrained, driven by a steadily increasing negative excess pore pressure with increasing loading rate. At the highest loading rate, under undrained conditions, the measured maximum negative excess pore pressures reach a steady limit, suggesting the occurrence of cavitation. This increase in anchor capacity with dimensionless velocity is captured using a 'backbone curve' interpretation framework that describes the change in capacity between the limiting values of drained and undrained anchor capacity. Calculation of drained anchor capacity is straightforward relative to the more challenging problem of calculating undrained capacity, particularly during cavitation. This was addressed separately through a numerical parametric study (pure undrained analysis) using a bounding surface soil model involving different water depths (cavitation potential), densities and embedment ratios. The numerical results are then synthesised into a simple extended analytical solution to allow estimation of undrained anchor capacity under different densities and water depths. [ABSTRACT FROM AUTHOR]

Offshore pipelines are important infrastructure for transporting oil and gas. They are subjected to cycles of high temperature and pressure variation during operation and shutdown periods, and are therefore susceptible to the stability problem of axial walking due to the asymmetry between the expansion and contraction. Axial walking can cause damage to subsea pipeline systems, for instance to the connected manifolds and steel catenary risers. This paper provides a complete analytical solution to examine the process of pipeline walking based on underlying principles of mechanics, considering the pipeline–seabed sliding response as rigid plastic. The analytical solution allows calculation of the cumulative displacement, strain, axial force and soil resistance along the pipeline under arbitrary temperature or internal pressure change histories, accounting for the coupled contributions from seabed slopes and end tension forces. A dimensionless parameter η is proposed to explain the triggering mechanism for walking by comparing the activating force to the soil resistance. New criteria are established to judge whether pipeline axial walking is possible. Calculation examples are presented in the final part of this paper to demonstrate the analytical solution. This study can be used as a rigorous benchmark and a simple practical tool to evaluate pipeline walking under arbitrary loading histories of temperature and internal pressure variations. [ABSTRACT FROM AUTHOR]

Layered soil conditions are common in marine sediments, and deduction of strength properties for thin interbedded layers is often challenging. Full-flow penetrometers such as T-bar are increasingly being used in offshore site investigations and show high potential for differentiating the shear strength transition between layers. This paper reports the results from large deformation finite-element analysis undertaken to provide insight into the response of a T-bar penetrometer as it continuously penetrates through stiff–soft–stiff clay layers. The numerical results are validated against data from a centrifuge model test. Trapped soil is observed for any nonsmooth interface as the T-bar penetrates from a stiff to a softer soil layer, which affects the measured resistance of the soft layer. The effect of a cavity above the advancing T-bar was also investigated. The presence of a cavity can increase the sharpness of the transition in resistance from one layer to another, which thus affects estimation of the boundary of the soft layer. The evolution of trapped soil from the top layer within the soft layer, and then its erosion in the bottom layer, were explored. The research found that the measured resistance profile in the soft layer is sensitive to the strength ratio between the top layer and soft layer, but the resistance of the bottom layer is more reliable. Based on deduced measurement parameters from the resistance profile, a new interpretation framework is proposed for interpreting the layer boundaries and undrained shear strength of the interbedded soft layer. [ABSTRACT FROM AUTHOR]

Background: Vascularized composite allografts (VCAs) allow reconstruction of devastating injuries and amputations, yet require lifelong immunosuppression that is associated with significant morbidity. Induction of immune tolerance of VCAs would permit widespread use of these procedures. VCAs are acquired from deceased donors most likely to be fully -MHC-mismatched (in contrast to living-related renal transplant donor-recipient pairs matched at one MHC haplotype). After achieving VCA tolerance in a swine model equivalent to clinical living-related renal transplants (single-haplotype MHC mismatches: e.g., "mother-daughter"/haploidentical), we tested our protocol in MHC class I, class II, and fully-MHC-mismatched pairs. Although class II mismatched swine demonstrated similar results as the haploidentical scenario (stable mixed chimerism and tolerance), our protocol failed to prevent rejection of class I and full mismatch VCAs. Here, we describe a new adapted conditioning protocol that successfully achieved tolerance across MHC class-I-mismatch barriers in swine. Methods: Swine were treated with non-myeloablative total body and thymic irradiation two days prior to infusion of bone marrow cells from an MHC class I-mismatched donor. They also received a short-term treatment with CTLA4-Ig (Belatacept®) and anti-IL6R mAb (Tociluzimab®) and were transplanted with an osteomyocutaneous VCA from the same donor. Results: Stable mixed chimerism and tolerance of MHC class-I-mismatched VCAs was achieved in 3 recipients. Allograft tolerance was associated with a sustained lack of anti-donor T cell response and a concomitant expansion of double negative CD4-CD8- T cells producing IL-10. Conclusions: This study demonstrates the first successful mixed chimerism-induced VCA tolerance in a large animal model across a MHC class-I-mismatch. Future studies aimed at fully-mismatched donor-recipient pairs are under investigation with this protocol. [ABSTRACT FROM AUTHOR]

Recent research on the topic of pile base resistance has demonstrated that the guidelines provided by existing design manuals and codes are rather conservative in the case of clayey soils under undrained conditions. With the aim of investigating this topic more rigorously, a computationally intensive study was carried out to quantify the effect of the soil rigidity index on the response of pile base resistance. A precise assessment of the results led to the formulation of hyperbolic relationships that capture the development of the base resistance as a function of settlement. The relationships were implemented in a beam column analysis and validated against a full axisymmetric numerical analysis and also with respect to field data from a pile test performed using an Osterberg cell near the pile base. The validation process demonstrated the usefulness of the method and recommendations arising with respect to mobilization of the pile base resistance. This study should, therefore, assist in the development of more scientifically based guidelines for pile design that balance safety and economy. [ABSTRACT FROM AUTHOR]

Most offshore wind turbines (OWTs) are supported by large-diameter monopiles, installed by impact driving. OWTs are dynamically sensitive structures, with a narrow design range for the eigenfrequency. Fatigue and serviceability limit states can be critical in design, so the foundation stiffness plays an important role. The pile installation process results in changes to the soil state, investigated here through large-deformation numerical analyses using the coupled Eulerian–Lagrangian approach with a hypoplastic constitutive relation to model the sand. The soil state is then mapped to a small-strain model to evaluate the effect of the installation process on the lateral response. Complementary physical modelling results from monopile installation and lateral load testing in a centrifuge provide confidence in the numerical model. Analyses for two different sands highlight commonalities and differences. Comparison with results featuring wished-in-place or jacked installation illustrates the effect of changes in the soil state on the lateral response. The results characterise the changes in soil state and allow quantification of their effects as impact driving tends to produce a stiffer lateral response, with the expected variations due to pile dimensions and sand relative density. Further research will provide insights into the role of pore fluid response during impact driving and investigate vibro-driven piles. [ABSTRACT FROM AUTHOR]

The volume of a submarine landslide is likely to be amplified by shear band propagation along a basal surface or spreading failure extension in the sliding layer. Although the mechanism of translational submarine landslides has been understood using the interpretation of shear band propagation, assessment of the limits of failure extension, either through shear band propagation or retrogressive spreading, remains a challenge due to the diversity of post failure mechanisms. The paper aims to explore all post failure possibilities and quantify failure initiation and extension accordingly, focusing on the upslope conditions. The different failure mechanisms are explored with the aid of the large deformation finite element modeling. Original criteria for scarp position, shear band length at slab failure, retrogression conditions and ultimate spreading limits are proposed, following the process zone approach considering force equilibrium of the sliding mass. Simplified analytical predictions are shown to agree well with the numerical observations. The findings and criteria presented in the study are expected to help assess the ultimate scale of upslope failure in submarine landslides, which is important in determining geohazard zonation of submarine landslides. Plain Language Summary: Submarine landslides are often huge compared to onshore counterparts, but why and how huge? Answering these questions will increase our understanding of submarine landslide evolution and help to assess risks of submarine landslide recurrence. For example, the Storegga Slide offshore Norway, which occurred ∼8,200 years ago, covered an area as large as UK and triggered tsunami waves seriously impacting nearby islands. A large submarine landslide might be initiated from localized failure within an embedded weak layer, followed by failure propagation along the weak layer and extensive slab failure in the overlying sliding layer. These two post‐failure phenomena may greatly increase the scale of submarine landslides. Here we simulate submarine landslides in different conditions and explore all possible upslope post‐failure mechanisms, using a large deformation numerical modeling method. Based on the observed mechanisms, we develop a new model and original criteria to predict the scarp position and failure extension limit of submarine landslides. Altogether, findings here are expected to help assess the ultimate scale of submarine landslides, which is important in determining geohazard zonation of submarine landslides. Key Points: We explore and quantify all upslope failure possibilities of submarine landslides through numerical modeling and theoretical analysesWe establish a framework for assessing failure initiation, covering different failure mechanismsWe propose simple predictions for scarp position and retrogression limit, which allows rapid assessment of scale of submarine landslides [ABSTRACT FROM AUTHOR]

The most commonly used procedure for prediction of the behaviour of laterally loaded piles is the P–y curve formulation, which gives a simple but efficient framework to predict the response of the pile. This framework is limited to a single direction of loading, while there are several situations in which a pile is subjected to lateral loads with varying direction, as for example in the case of wind or wave loads. Here an extended framework for P–y curve modelling is presented, in which several springs are considered around the pile perimeter at each depth. The advantage of this framework is that it remains as simple and practical as the original P–y curve method and does not need any further information or parameters. A procedure is proposed for the extension of a given unidirectional model to the corresponding multi-directional one. The effects of multi-directional loading are discussed based on the simulation results. With a change in loading direction, misalignment between load direction and total displacement occurs. In addition, this quite simple model enables deduction of the profile of irreversible soil displacements around the pile at various depths. [ABSTRACT FROM AUTHOR]

This technical note presents simplified parametric solutions for the axial response of surface-laid submarine pipelines subjected to axial drag from debris flows. In assessing the response of pipelines impacted by debris flow emanating from a submarine landslide, both normal and axial responses must be considered. Previous work has indicated that these can be decoupled, at least as a first-stage analysis. The most critical aspect of axial drag is the potential for the pipeline to buckle. However, to make preliminary estimates of displacements and forces along the pipeline prior to buckling, simple assumptions of elastic pipeline response with elastic perfectly plastic interaction with the seabed are justified. These allow the development of parametric solutions that contain only three nondimensional quantities. This technical note documents the solutions and illustrates their application for some typical input conditions. [ABSTRACT FROM AUTHOR]

This paper describes a centrifuge study using a range of penetrometer tests (T-bar, piezocone and free-fall piezocone) to explore strength changes in a reconstituted, normally consolidated, natural calcareous silt. Various penetrometer test procedures were applied to measure the penetration resistances including monotonic, cyclic and twitch-type movements as well as pauses for pore pressure dissipation. These mobilised combinations of partial or full remoulding, strain softening, consolidation and viscous rate effects. The penetrometer resistance – representing a proxy for strength – reduced by a factor of 4·1 from drained to undrained conditions (at the lowest fully undrained penetration rate). In undrained conditions, viscous enhancement of the penetration resistance raised the tip and shaft resistance in free-fall piezocone tests by ∼2·8 and ∼3·6 times, respectively. The 'restart' resistance immediately after the dissipation tests was ∼2·5 times higher than the resistance prior to dissipation, giving an indication of consolidation-induced strength gain. The 'twitch' test (using sequential steps decreasing the velocity) captured drainage and viscous rate effects, and also gave a 'restart' resistance that showed even greater consolidation effects than from a dissipation test. Overall, the different penetrometer test types and procedures measured resistances in the same soil sample that varied by a factor exceeding 20 from highest to lowest, resulting from different penetration rates and history, due to strain rate, strain level (or remoulding) and consolidation. An expression for the monotonic penetration resistance combining drainage and viscous rate effects was fitted to the response of all tests, spanning >7 orders of magnitude in strain rate. [ABSTRACT FROM AUTHOR]

Transplantation of vascularized composite allografts (VCAs) provides a means of restoring complex anatomical and functional units following burns and other disfigurement otherwise not amenable to conventional autologous reconstructive surgery. While short- to intermediate-term VCA survival is largely dependent on patient compliance with medication, the myriad of side effects resulting from lifelong systemic immunosuppression continue to pose a significant challenge. Topical immunosuppression is therefore a logical and attractive alternative for VCA. Current formulations are limited though, by poor skin penetration but this may be mitigated by conjugation of immunosuppressive drugs to TyroSpheres for enhanced delivery. Therefore, we investigated the topical application of FK506-TyroSpheres (in the form of a gel dressing) in a clinically relevant nonhuman primate VCA model to determine if allograft survival could be prolonged at reduced levels of maintenance systemic immunosuppression. Six Major Histocompatibility Complex (MHC)-mismatched cynomolgus macaques (Macaca fascicularis) served as reciprocal donors and recipients of radial forearm fasciocutaneous flaps. Standard Bacitracin ointment and FK506-TyroSpheres were applied every other day to the VCAs of animals in groups 1 (controls, n = 2) and 2 (experimental, n = 4), respectively, before gradual taper of systemic FK506. Clinical features of VCA rejection still developed when systemic FK506 fell below 10 ng/ml despite application of FK506-TyroSpheres and prolonged VCA survival was not achieved. However, unwanted systemic FK506 absorption was avoided with TyroSphere technology. Further refinement to optimize local drug delivery profiles to achieve and maintain therapeutic delivery of FK506 with TyroSpheres is underway, leveraging significant experience in controlled drug delivery to mitigate acute rejection of VCAs. [ABSTRACT FROM AUTHOR]

Field observations of semitaut mooring systems have shown severe trench development in front of suction caissons. Trenches extend back from where the chain emerges from the seabed under ambient mooring loads to relatively close to the caisson and with depths approaching the padeye depth. To help understand the process, a coupled Eulerian–Lagrangian (CEL) approach has been used to apply cyclic loading to a mooring chain system, treating the chain as a series of linked cylindrical elements and the soil as a strain-softening Tresca material. The chain extended through the soil into the water column, and cyclically changing boundary conditions were applied to the far end of the chain to reflect a typical mooring layout and metocean conditions. Despite rather idealized conditions, with loading restricted to the vertical plane of the chain and no consideration of hydrodynamic effects, a stable trench profile developed after only a few cycles of loading. The chain profile straightened during the cycles, with the section nearest to the padeye gradually cutting deeper into the soil and with the amplitude of cyclic motions of the chain, and hence tendency for a trench to form, increasing at shallower depths. The magnitude of soil resistance acting on the chain reduced by increasing cycles, with particularly low resistance in the zone where the trench was most developed. The long-term longitudinal profile of trenching was predicted based on the current modeling and was found comparable to that inferred from field observations, even without consideration of hydrodynamic and out-of-plane effects. [ABSTRACT FROM AUTHOR]

This paper reports the use of optical fiber Bragg-grating (FBG) sensors to monitor the stress waves generated below ground during pile driving, combined with measurements using conventional pile driving analyzer (PDA) sensors mounted at the pile head. Fourteen tubular steel piles with a diameter of 508 mm and embedded length-to-diameter ratios of 6∶20 were impact driven at an established chalk test site in Kent, United Kingdom. The pile shafts were instrumented with multiple FBG strain gauges and pile head PDA sensors, which monitored the piles' responses under each hammer blow. A high-frequency (5 kHz) fiber optic interrogator allowed a previously unseen resolution of the stress wave propagation along the pile. Estimates of the base soil resistances to driving and distributions of shaft shear resistances were found through signal matching that compared the time series of pile head PDA measurements and FBG strains measured below the ground surface. Numerical solutions of the one-dimensional wave equation were optimized by taking account of the data from multiple FBG gauges, leading to significant advantages that have potential for widespread application in cases where high-resolution strain measurements are made. [ABSTRACT FROM AUTHOR]

Summary: Soil–water interaction is a pivotal process in many underwater geohazards such as underwater landslides where soil sediments gradually evolve into turbidity currents after interactions with ambient water. Due to the large deformations, multiphase interactions and phase changes this involves, investigations from numerical modelling of the transition process have been limited so far. This study explores a simple numerical replication of such soil–water mixing with respect to changes in average strength using smoothed particle hydrodynamics (SPH). A uniform viscoplastic model is used for both the solid‐like and fluid‐like SPH particles. The proposed numerical solution scheme is verified by single‐phase dam break tests and multiphase simple shear tests. SPH combinations of solid‐like and fluid‐like particles can replicate the clay–water mixture as long as the liquidity index of the solid‐like particles is larger than unity. The proposed numerical scheme is shown to capture key features of an underwater landslide such as hydroplaning, water entrainment and wave generation and thus shows promise as a tool to simulate the whole process of subaquatic geohazards involving solid–fluid transition during mass transport. [ABSTRACT FROM AUTHOR]

This study investigated the change in monotonic and cyclic capacity of a plate anchor across different degrees of consolidation in dense sand. To quantify the effect of consolidation on anchor capacity, a framework is introduced and validated using centrifuge model anchor test data. The centrifuge tests considered a rectangular plate loaded at varying rates in dense sand, under both monotonic and irregular cyclic conditions, at a fixed embedment depth and with a horizontal load inclination (at the seabed). In order to vary from drained to undrained conditions, the sand was saturated using both water and a viscous pore fluid with viscosity approximately 700 times higher than water. The anchor's ultimate monotonic capacity in dense sand increased by up to 173% as the consolidation response evolved from drained to undrained with generation of dilation-induced suction. This increase in capacity across the consolidation regime can be adequately quantified using the proposed framework; however, uncertainty arises in achieving the theoretical undrained capacity. Both drained and undrained irregular cyclic loading resulted in anchor capacity increases of up to 33%, attributed to soil volume changes associated with cyclic densification under drained cyclic loading and excess pore pressure dissipation under undrained cyclic loading. [ABSTRACT FROM AUTHOR]

The majority of periprosthetic joint infections occur shortly after primary joint replacement (<3 months) and require the removal of all implant components for the treatment period (~4 months). A clinically relevant animal model of periprosthetic infection should, therefore, establish an infection with implant components in place. Here, we describe a joint replacement model in the rat with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components inoculated at the time of surgery by methicillin‐sensitive Staphylococcus aureus (S. aureus), which is one of the main causative microorganisms of periprosthetic joint infections. We monitored the animals for 4 weeks by measuring gait, weight‐bearing symmetry, von Frey testing, and micro‐CT as our primary endpoint analyses. We also assessed the infection ex vivo using colony counts on the implant surfaces and histology of the surrounding tissues. The results confirmed the presence of a local infection for 4 weeks with osteolysis, loosening of the implants, and clinical infection indicators such as redness, swelling, and increased temperature. The utility of specific gait analysis parameters, especially temporal symmetry, hindlimb duty factor imbalance, and phase dispersion was identified in this model for assessing the longitudinal progression of the infection, and these metrics correlated with weight‐bearing asymmetry. We propose to use this model to study the efficacy of using different local delivery regimens of antimicrobials on addressing periprosthetic joint infections. Statement of clinical significance: We have established a preclinical joint surgery model, in which postoperative recovery can be monitored over a multi‐week course by assessing gait, weight‐bearing, and allodynia. This model can be used to study the efficacy of different combinations of implant materials and medication regimens. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1101‐1112, 2020 [ABSTRACT FROM AUTHOR]

Gigantic submarine landslides pose a significant threat to offshore infrastructures and may be initiated by an inconspicuous weakened zone, followed by catastrophic shear band propagation under the effect of strain softening. Much attention has been paid over the last two decades to unidirectional (parallel to the travel direction of sliding mass) shear band propagation (SBP) related exclusively to an initiation zone that is wide relative to the SBP direction. The paper investigates for the first time the mechanisms of more realistic planar shear band propagation via numerical modelling including finite element and finite difference analyses. Rather than propagating only along the travel direction for a 1D shear band in a plane-strain slope, the multidirectional propagation behaviour of a planar shear band depends significantly on the aspect ratio of the initiation zone. New criteria for catastrophic propagation of a planar shear band are proposed and are shown to be in good agreement with the numerical results. The criteria with respect to the initiation zone area can be incorporated easily within a GIS-based stability analysis of catastrophic submarine landslides, facilitating robust hazard analysis for offshore developments. [ABSTRACT FROM AUTHOR]

This paper attempts to explain how a normally consolidated lakebed sediment can have an undrained strength ratio of approximately unity, when the lithic component of the sediment is less than 3% by volume. The structured clay framework, coupled with sensitivity measurements of the sediment, show that the structure retains a very high strength in a remoulded state. Close examination of the sediment indicates a significant microfossil presence. When considered together with the depositional environment and local water chemistry, this suggests that the soil strength arises from a structural matrix of biofilm adhering to the clay and microfossil particles, which is enhanced by cross-linking due to the presence of multi-valent cations in the local water. Laboratory-scale piezocone, piezoball and T-bar penetrometer tests show that the strength and consolidation characteristics can be significantly altered by changes in the pore water chemistry, an observation that should be considered in geotechnical design for such soils. [ABSTRACT FROM AUTHOR]

Summary: Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor‐specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post‐transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality. [ABSTRACT FROM AUTHOR]