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[EN] This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and TRM-reinforced masonry building structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond manner. The prototype was tested by applying pseudo-dynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (i) on the as-built structure and (ii) after the repair and the application of Textile Reinforced Mortar (TRM) material. A series of non-linear numerical simulations were performed adopting the ABAQUS/Explicit FE software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM technique to increasing the strength of low-rise old masonry building structures., The authors would like to express their gratitude to the Spanish Ministry of Economy, Industry and Competitiveness for the funding provided (BIA 2014-59036-R-AR), and also to the Grupo Mapei and Grupo Puma for their invaluable assistance during the experimental tests.

Textile-reinforced mortar (TRM) is a strengthening material in which textiles are attached to reinforced concrete (RC) structures using an inorganic matrix. Although many studies on structural behavior, various factors that affect TRM behavior could not be determined clearly. Especially, the uncertainty in bonds due to inorganic materials was not considered. In this study, the flexural behavior of TRM-strengthened beams was determined considering intermediate crack debonding occurred. The TRM beam strengthening limit and TRM coefficients were defined considering the possibility of premature failure and experimental results of four other research on 22 specimens. Therefore, it is expected that a conservative design would be possible when the suggested strengthening limit coefficient is applied.

Background: In the course of plaque psoriasis, tissue resident memory cells (TRM) are responsible for the phenomenon of “immune memory” of lesions, i.e., the appearance of recurrences of lesions in the same location, as well as Koebner phenomenon. We present results determining the location and amount of TRM in psoriatic lesions in patients suffering from plaque psoriasis, as well as an analysis of the relationship between TRM markers expression and the duration and severity of the disease. Methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and tissue expression of cytokines (IL-17, IL-22) in the lesional psoriatic skin of 32 patients compared with 10 healthy skin samples were evaluated by immunohistochemistry. Results: The presence of TRM markers in both the epidermis and skin with psoriatic eruptions was demonstrated in much higher amounts compared with the skin of healthy volunteers. A significant positive relationship was demonstrated between the expression of TRM markers in patients with plaque psoriasis and the duration of skin lesions. There was no relationship between the amount of TRM and the severity of plaque psoriasis. Conclusions: A thorough understanding of the mechanisms responsible for the development and relapse of plaque psoriasis may contribute to the implementation of more effective therapies.

In health, the non-recirculating nature and long-term persistence of tissue-resident memory T cells (TRMs) in tissues protects against invading pathogens. In disease, pathogenic TRMs contribute to the recurring traits of many skin diseases. We aimed to conduct a systematic literature review on the current understanding of the role of TRMs in skin diseases and identify gaps as well as future research paths. EMBASE, PubMed, SCOPUS, Web of Science, Clinicaltrials.gov and WHO Trials Registry were searched systematically for relevant studies from their inception to October 2020. Included studies were reviewed independently by two authors. This study was conducted in accordance with the PRISMA-S guidelines. This protocol was registered with the PROSPERO database (ref: CRD42020206416). We identified 96 studies meeting the inclusion criteria. TRMs have mostly been investigated in murine skin and in relation to infectious skin diseases. Pathogenic TRMs have been characterized in various skin diseases including psoriasis, vitiligo and cutaneous T-cell lymphoma. Studies are needed to discover biomarkers that may delineate TRMs poised for pathogenic activity in skin diseases and establish to which extent TRMs are contingent on the local skin microenvironment. Additionally, future studies may investigate the effects of current treatments on the persistence of pathogenic TRMs in human skin.

This paper describes methods, procedures, and results of cyclic loading tensile tests of a PBO FRCM composite. The main objective of the research is the evaluation of the effect of low- and high-cycle fatigue on the composite tensile properties, namely the tensile strength, ultimate tensile strain, and slope of the stress–strain curve. To this end, low- and high-cycle fatigue tests and post-fatigue tests were performed to study the composite behavior when subjected to cyclic loading and after being subjected to a different number of cycles. The results showed that the mean stress and amplitude of fatigue cycles affect the specimen behavior and mode of failure. In high-cycle fatigue tests, failure occurred due to progressive fiber filaments rupture. In low-cycle fatigue, the stress–strain response and failure mode were similar to those observed in quasi-static tensile tests. The results obtained provide important information on the fatigue behavior of PBO FRCM coupons, showing the need for further studies to better understand the behavior of existing concrete and masonry members strengthened with FRCM composites and subjected to cyclic loading.

We assess tensile performance of Steel Reinforced Grout (SRG) and Fabric Reinforced Cementitious Matrix/Textile Reinforced Mortar, upon exposure to aggressive environments. Galvanized and brass-coated Ultra High Tensile Strength Steel fabrics are considered for SRG, while carbon, AR-glass, basalt and PBO fabrics are investigated for TRM, in a common cement mortar. Exposure to the aggressive environments is realized by specimen immersion for 1000 h (41.6 days) at controlled temperature in distilled water as well as alkaline, saline and acid solutions. Mechanical performance of rectangular 1-ply coupons is assessed in uni-axial traction: Ultimate strength and elongation, dissipated energy at failure and environmental conversion factors for design values are calculated and compared. It is found that significant performance difference exists in dependence of the aggressive environment under consideration. As a result, careful selection of the reinforcing fabric leads to substantial advantage in terms of durability, that should be capitalized upon at the design stage. A simple material selection matrix is presented which suggests the best reinforcing textile/aggressive environment combination for design purposes.

Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in tumor patients are poorly understood. Two types of memory T cells have been described according to their traffic pathways: recirculating and tissue-resident memory T cells. Recirculating tumor-specific memory T cells are found in the cell infiltrate of solid tumors, in the lymph and in the peripheral blood, and they constantly migrate in and out of lymph nodes, spleen, and bone marrow. Tissue-resident tumor-specific memory T cells (TRM) permanently reside in the tumor, providing local protection.Anti-PD-1/PD-L1, a type of immune checkpoint blockade (ICB) therapy, can considerably re-invigorate T cell response and lead to successful tumor control, even in patients at advanced stages. Indeed, ICB has led to unprecedented successes against many types of cancers, starting a ground-breaking revolution in tumor therapy. Unfortunately, not all patients are responsive to such treatment, thus further improvements are urgently needed. The mechanisms underlying resistance to ICB are still largely unknown. A better knowledge of the dynamics of the immune response driven by the two types of memory T cells before and after anti-PD-1/PD-L1 would provide important insights on the variability of the outcomes. This would be instrumental to design new treatments to overcome resistance.Here we provide an overview of T cell contribution to immunity against solid tumors, focusing on memory T cells. We summarize recent evidence on the involvement of recirculating memory T cells and TRM in anti-PD-1/PD-L1-elicited antitumor immunity, outline the open questions in the field, and propose that a synergic action of the two types of memory T cells is required to achieve a full response. We argue that a T-centric vision focused on the specific roles and the possible interplay between TRM and recirculating memory T cells will lead to a better understanding of anti-PD-1/PD-L1 mechanism of action, and provide new tools for improving ICB therapeutic strategy.

A growing environmental awareness is gradually changing the entire economic system and consequently, the building materials sector is increasingly interested in innovative sustainable solutions. The use of plant fibres as reinforcement in inorganic composite systems, generally referred to as Textile Reinforced Mortar (TRM), represents an innovative alternative to the use of more traditional high-strength inorganic fibres, which reduces the environmental impact of the composite. However, there are several unsolved issues regarding the correct mechanical behaviour of such innovative systems. Various studies have been conducted to assess the fibre-to-mortar bond properties and to investigate the tensile behaviour of TRMs based on plant textiles, such as flax, hemp, coir, sisal, and jute. Moreover, there is still a lack of experimental evidence concerning the efficiency of the composite material once applied to structural elements. Therefore, this paper reports on an experimental study on the shear capacity of walls strengthened by two TRMs characterised by a different amount of textile reinforcement. The experimental results are discussed and compared with the results of theoretical models derived from formulations proposed by the standards in this field. This study shows that Flax-TRM reinforcement enhances the strength and ductility of a masonry assemblage, confirming the potential utility of such materials. Furthermore, it points out some limitations of this reinforcement technique and paves the way for future studies aimed at improving the efficiency of the entire system.

Fibre-reinforced cementitious matrix (FRCM) composites have been effectively used during the last ten years for the strengthening of existing concrete and masonry structures. These composite materials are made of medium- and high-strength fibre meshes embedded in inorganic matrices. Synthetic fibres are the ones that are currently the most used, however, natural fibres, such as basalt fibres, have recently been receiving growing attention. This work presents an extensive experimental study on the mechanical characterisation of a primed basalt fibre bidirectional grid. Fifty monotonic tensile tests on basalt grid strips were performed by varying different parameters, such as the dimension of the specimens, the clamping system, the measurement system and the test rate. Some of the tests were carried out using a video-extensometer to measure each specimen&rsquo, s strain. The aim of the study was to find the most suitable setup for the tensile characterisation of basalt textiles, in particular, to prevent slippage of the samples at the gripping area and fully exploit the tensile capacity of the grid.

The proliferation of the Internet of Things (IoT) caused new application needs to emerge as rapid response ability is missing in the current IoT end-devices. Therefore, Fog Computing has been proposed to be an edge component for the IoT networks as a remedy to this problem. In recent times, cyber-attacks are on the rise, especially towards infrastructure-less networks, such as IoT. Many botnet attack variants (Mirai, Torii, etc.) have shown that the tiny microdevices at the lower spectrum of the network are becoming a valued participant of a botnet, for further executing more sophisticated attacks against infrastructural networks. As such, the fog devices also need to be secured against cyber-attacks, not only software-wise, but also from hardware alterations and manipulations. Hence, this article first highlights the importance and benefits of fog computing for IoT networks, then investigates the means of providing hardware security to these devices with an enriched literature review, including but not limited to Hardware Security Module, Physically Unclonable Function, System on a Chip, and Tamper Resistant Memory.

Current Topics and Trends on Durability of Building Materials and Components: Proceedings of the XV edition of the International Conference on Durability of Building Materials and Components (DBMC 2020), Textile-reinforced mortar (TRM) composites have received extensive attention as a sustainable solution for seismic strengthening of masonry and historical structures. This new system is composed of textile fibers embedded in an inorganic matrix and is applied on the masonry and the concrete substrate surface as an externally bonded reinforcement (EBR) system. The bond at the textile-to-mortar interfaces is the main stress-transfer mechanism and, therefore, should be thoroughly investigated. Furthermore, the effectiveness of TRMs in improving the seismic performance of existing structures is highly dependent on the durability of its components, materials, textile-to-mortar bond, and their long-term behavior. Due to the novelty of these materials in application to masonry structures, several aspects related to the durability and long-term performance of them are still not clear. To that end, a new study has been launched that looks at the time effect on the mechanical properties and bond behavior between fiber and mortar. For this purpose, two different hydraulic lime-based mortars, as well as steel and glass fibers, are used to investigate the effect of mortar age on the TRM system after 180 days. The results show that at the early age of mortars, their mechanical properties, and the bond behavior of textile-to-mortar have been increased. Another critical point to remember is that by increasing the mortar age, textile-to-mortar bond and mortar strength are decreased., FEDER funds through the Competitivity Factors Operational Programme (COMPETE) and by national funds through the Foundation for Science and Technology (FCT) within the scope of the project POCI-01-0145-FEDER-007633. The support to the first author through grant SFRH/BD/131282/2017 is acknowledged. Also, the authors would like to thank the Kerakoll Company for supplying the GeoCalce Fino mortar as well as GeoSteel G600 fibers

Application of textile-reinforced mortar (TRM) composites have for strengthening of existing structures or for production of new thin structural elements has attracted a growing recent attention. TRMs are made of continuous fibres (in the form of fabric or mesh) embedded in an inorganic matrix forming a composite material. The large variety of available fabric (glass, steel, basalt, PBO, etc.) and mortar types (cement-based, lime-based, etc.) leads to a wide range of mechanical properties making these composites suitable for fit-for-purpose design applications. Due to mechanical and hygrothermal compatibility issues, lime-based TRMs are the preferred choice for application to existing masonry and historical structures. Meanwhile, cement-based TRMs are usually employed for application to existing concrete or new masonry structures. The main characteristic behaviour of these composites is the tension stiffening response and distributed cracking under tensile loads which are highly influenced by the fabric-to-mortar bond behaviour. Fundamental understanding of this mechanism (the fabric-to-mortar bond behaviour) and parameters affecting that are therefore of critical importance of designing TRM composites with desired properties. This paper presents and overview of the recent studies we performed during the lat years for better udnertanding this mechanism., Portuguese Scientific Foundation (FCT) for the financial support through grant SFRH/BD/131282/2017

Application of textile-reinforced mortars (TRMs) for externally bonded reinforcement of existing masonry structures has received a considerable recent attention. The mechanical behaviour of these composites, which are composed of continuous fibers embedded in an organic matrix, and their effectiveness in improving the performance of strengthened structures are highly dependent on the fiber-to-mortar bond behaviour as well as the bond between TRM system and substrate. Understanding the long-term performance of these mechanisms is therefore of critical importance for design of durable TRM composites and ensuring the safety of strengthened structures. To address this aspect, the effect of freeze-thaw cycles on the textile-to-mortar bond behaviour is experimentally investigated and discussed in this paper. The results illustrate a significant deterioration of the textile-to-mortar bond performance in the studied composites., FEDER funds through the Competitivity Factors Operational Programme (COMPETE) and by national funds through the Foundation for Science and Technology (FCT) within the scope of project POCI-01-0145-FEDER007633. The support to the first author through grant SFRH/BD/131282/2017

Many European heritage and modern buildings have a very high seismic vulnerability due to their masonry-based structural system. Although these structures have a low capacity to resist tension or shear stresses, even nowadays some new buildings are using these materials as structural system in many seismic areas. The main objective of this paper is the use of high order ANSYS code 3D elements in the numerical modelling of masonry structures. For this purpose, FE models corresponding to standard tests were made and calibrated using results of experimental tests. In particular, this document will analyze the resistant behavior to uniaxial and diagonal compression in brick samples. The numerical micromodel has been developed using non-linear hexaedrical 8 and 20 nodes tridimensional elements to represent brick and mortar, such as solid185 and solid186, in contrast to traditional FE models which use element solid65 as finite element to represent masonry behavior. Drucker-Prager and Rankine models have been used to study the compression-tension failure surface, adding a linear hardening-softening-dilatation behavior. Moreover, fracture-energies based cohesive zones have been added to contacts between mortar and bricks, in order to allow debonding failure between these two materials. These modelling methods prove to be a valid technique to simulate brick masonry behavior according to experimental results and will be used as a base to develop future parametric FEM analysis to study TRM reinforced masonry specimens.

Due to inadequacies of reinforcement design in older structures and changes in building codes, but also the change of building use in existing structures, reinforced concrete (RC) beams often require upgrading during building renovation. The combined shear and flexural strengthening with composite materials, fibre-reinforced polymer sheets (FRP) and textile reinforced mortars (TRM), is assessed in this study. An experimental campaign on twelve half-scale retrofitted RC beams is presented, looking at various parameters of interest, including the effect of the steel reinforcement ratio on the retrofit effectiveness, the amount of composite material used for strengthening and the effect of the shear span, as well as the difference in effectiveness of FRP and TRM in strengthening RC beams. Significant effects on the shear capacity of composite retrofitted beams are observed for all studied parameters. The experimental study is used as a basis for developing a detailed finite element (FE) model for RC beams strengthened with FRP. The results of the FE model are compared to the experimental results and used to design a parametric study to further study the effect of the investigated parameters on the retrofit effectiveness.

The use of Textile Reinforced Mortar (TRM) systems is emerging as a suitable solution for strengthening historical masonry buildings, as they are made of compatible materials often resulting in limited and reversible interventions. Moreover, TRM systems reinforced by basalt textile are a very promising solution. This study presents the results of single shear-lap tests intended at defining and comparing the effectiveness of three reinforced basalt TRM-masonry systems characterized by different strengthening ratios. These systems have been obtained by inserting one, two or three basalt grids in the TRM composite. The experimental results show that a slippage of the fiber roving within the mortar matrix frequently occurs in the reinforced system characterized by a low strengthening ratio; the increase in fiber grid density often results in a brittle debonding between the lower and the upper layer of mortar matrix. The results show that a high strengthening ratio may result in decreasing the strengthening performances.

Application of lime-based textile-reinforced mortars (TRMs) for strengthening of masonry structures have received a growing attention in recent years. An extensive effort has been devoted to understanding of the performance of these composites and their effectiveness in improving the seismic safety of existing masonry structures. Nevertheless, several aspects regarding the durability and mechanics of these composites still remain unknown. This letter is an effort on highlighting those aspects considering both experimental and numerical modelling approaches.

Fiber-reinforced composites can be arranged in the form of bi-dimensional grids and employed as internal reinforcement of mortar plasters to realize composite reinforced mortar (CRM) systems. Recently, CRM were applied as externally bonded reinforcement of existing masonry members showing promising improvements of load-carrying and deformation capacities. However, since CRM systems are still in their infancy, limited research is available regarding their mechanical properties and their bond behavior with respect to masonry substrates. In this paper, a series of experimental tests are performed on a CRM system comprising a glass fiber-reinforced composite grid and a lime-based matrix. Namely, tensile tests of bare grid yarns and of CRM coupons, shear tests of grid joints, and single-lap direct shear tests of CRM-masonry joints were performed. These tests are aimed at providing a comprehensive mechanical characterization of the CRM, which results can be used to design strengthening applications with this system. Namely, the tensile properties of bare grid yarns in warp and weft direction are obtained and compared with those of CRM coupons tested following the indications of the Italian and U.S. acceptance criteria for inorganic-matrix composites. Furthermore, the grid joints are subjected to shear tests to determine if the yarns orthogonal to the applied load direction provide a contribution to the system load-carrying capacity. Finally, CRM-masonry joints are subjected to single-lap direct shear tests to study the CRM bond behavior. This work provides an insight on the behavior of CRM that can be useful to formulate reliable design procedures for these systems.

Inorganic composites for enhancing the in-plane shear capacity of masonry walls with irregular texture were investigated on twenty-one panels under diagonal compression tests. Three specimens were used as control and twelve specimens were strengthened with two Fibre Reinforced Mortars (FRM-A and FRM-B), characterized by a different content of fibres embedded in the lime-based matrix. The remaining six specimens were strengthened with Fabric Reinforced Cementitious Mortars (FRCM), consisting in a GFRP grid embedded in a fibre reinforced matrix (the same used for FRM-A). The influence of single-side and double-side strengthening configurations on the capacity of strengthened panels was also investigated, to point out the reduction in strengthening effectiveness in case of single-sided applications. The results showed that all the inorganic composites adopted for the strengthening techniques provided a substantial increase of shear capacity. The grid in FRCM strengthened panels played an important role in both strength and deformation capacity at peak. The different fibres content (lower than 50% in weight) in FRM systems slightly affected the overall performance of panels. Finally, analytical predictions of experimental results were reported and discussed and a preliminary analytical model for estimating the FRM shear contribution was proposed, obtaining a good agreement with test results.

Lime-based textile-reinforced mortars (TRM) have recently found a growing interest for repair and strengthening of masonry and historical structures. Despite extensive experimental and numerical investigations performed in the last years on the performance of these composites, there is still a lack of fundamental understanding of the fabric-to-mortar bond behaviour (as one of the main mechanisms affecting the cracking and nonlinear response of these composites) and the parameters affecting that. This paper, aimed at addressing this gap, presents a comprehensive experimental and analytical investigation on how the test setup, embedded length, load rate, mortar age and fabric configuration affect the bond behaviour in lime-based TRMs. In total 160 pull-out tests are performed on a glass-based and a steel-based TRM commonly used for strengthening of masonry structures. The results contribute to standardization of the test procedures for characterization of the fabric-to-mortar bond behaviour, to fundamental understanding of this mechanism and to optimization of the design of these composites for enhancing their mechanical response., This work was partly financed by FEDER funds through the Competitivity Factors Operational Programme (COMPETE) and by national funds through the Foundation for Science and Technology (FCT) within the scope of project POCI-01-0145-FEDER-007633. The support to the first author through grant SFRH/BD/131282/2017 is acknowledged.

This paper presents the results of direct tensile tests performed on six different FRCM (fabric reinforced cementitious matrix) strengthening systems used for masonry structures. The emphasis was placed on the determination of the mechanical parameters of each tested system and a comparison of their tensile behaviour in terms of first crack stress, ultimate stress, ultimate strain, cracking pattern, failure mode and idealised tensile stress-strain curve. In addition to the basic mechanical tensile parameters, accidental load eccentricities, matrix tensile strengths, and matrix modules of elasticity were estimated. The results of the tests showed that the tensile behaviour of FRCM composites strongly depends on the parameters of the constituent materials (matrix and fabric). In the tests, tensile failure of reinforcement and fibre slippage within the matrix were observed. The presented research showed that the accidental eccentricities did not substantially affect the obtained results and that the more slender the specimen used, the more consistent the obtained results. The analysis based on a rule of mixtures showed that the direct tensile to flexural tensile strength ratio of the matrixes used in the test was 0.2 to 0.4. Finally, the tensile stress–strain relationship for the tested FRCMs was idealised by a bi- or tri-linear curve.

Fabric-reinforced cementitious matrix (FRCM) strengthening is an innovative technology for effective reduction of seismic vulnerability of existing masonry and historical structures. At present, numerical modeling strategies for evaluation of the in- and out-of-plane performance of masonry structures strengthened with these composites are in their embryonic stage. The present chapter is aimed at presenting two alternative approaches to such strategies. In particular, a detailed 3D heterogeneous and an inexpensive homogenization approach are reviewed. In the first model, brick and mortar joints are meshed separately with 3D eight-noded elements, whereas FRCM is discretized using trusses (fiber grid) and 3D eight-noded elements (cementitious matrix). These 3D elements are made in all cases with a softening and damage behavior with plasticization, both in tension and compression, using the concrete damage plasticity model. In the homogenization approach, masonry is substituted with an equivalent nonlinear orthotropic material exhibiting softening. The elementary cell is discretized using a few triangular elastic elements (bricks) and holonomic interfaces (joints) in which all the nonlinearities are lumped. The FRCM reinforcement is applied to the homogenized masonry using equivalent trusses with limited tensile strength and fragile behavior, connecting adjoining rigid elements. Equivalent mechanical properties of the trusses can be eventually tuned accounting for FRCM debonding or rupture of the fibers. The pros and cons of the two numerical procedures are discussed with respect to their reliability in fitting experimental force–displacement curves and crack patterns, as well as to the rather different computational effort required by the two strategies.

The strengthening of masonry structures using composite-based solutions has received significant research attention in recent years due to their proved considerable influence on enhancing structural characteristics, for example, stiffness and strength. In spite of the all achieved advances, numerous drawbacks have been noticed, in particular when conventional fiber-reinforced polymers are used. Thus novel techniques such as textile-reinforced mortar (TRM) have been introduced to overcome these issues. This chapter addresses key aspects of nonlinear finite element modeling of TRM composites. It mainly discusses the macromodeling approach as it requires fewer details (material characteristics) and less computational effort with respect to the micromodeling strategy, making it possible to use this approach in complex practical projects. Experimentally observed behaviors and characterization of required material properties are considered and knowledge gaps are highlighted. Finally, a series of numerical macromodeling applications on masonry structures are discussed, involving different construction materials. Pushover analyses are conducted to assess the influence of TRMs on both in-plane and out-of-plane seismic responses, (undefined)

Raw earth is one of the most widely used building materials and is employed in different techniques, among which adobe and rammed earth are the most common. The respective structural systems, like in masonry buildings, acceptably withstand against gravity loads, though they are significantly vulnerable to earthquakes. Moreover, a great percentage of the World’s population is still inhabited in such environments, which are endangered by future earthquakes. The current article investigates the seismic in-plane performance of an I-shaped rammed earth component by means of advanced nonlinear finite element modelling. In this regard, conventional pushover analyses were conducted to evaluate load/displacement capacities and to assess probable failure modes. It was observed that the component fails mainly due to detachment of the wing walls from the web wall and due to occurrence of diagonal shear cracks at the web. Subsequently, the application of Textile Reinforced Mortar (TRM) strengthening solution to the component was studied and shown to be able to maintain the integrity of the component for larger lateral load levels. Finally, the reliability of the pushover analyses to predict the seismic response was evaluated by comparison with outcomes from incremental nonlinear dynamic analysis., This work was financed by FEDER funds through the Competitively Factors Operational Programme – COMPETE and by national funds through FCT - Foundation for Science and Technology within the scope of projects POCI-01-0145-FEDER-007633 and POCI-01-0145-FEDER-016737 (PTDC/ECMEST/2777/2014). The support from grant SFRH/BPD/97082/2013 is also acknowledged.

Previous studies have suggested that HLA-E may have a significant role in the outcome of matched unrelated hematopoietic stem cell transplantation (HSCT), especially for patients with acute leukemia. We used Center for International Blood and Marrow Transplant Research data and samples of 1840 adult patients with acute leukemia and their 10/10 HLA-matched unrelated donors to investigate the impact of HLA-E matching status as well as of donor/recipient (D/R) HLA-E genotype on post-HSCT outcome. Both patients and donors were HLA-E genotyped by next-generation sequencing. All patients received their first transplant in complete remission between 2000 and 2015. Median follow-up time was 90 months. Overall survival, disease-free survival (DFS), transplant-related mortality (TRM), and relapse incidence were primary endpoints with statistical significance set at .01. D/R HLA-E genotype analysis revealed a significant association of donor HLA-E*01:03/01:03 genotype with DFS (hazard ratio [HR] = 1.35, P = .0006) and TRM (HR = 1.41, P = .0058) in patients who received T cell replete (ie, without in vivo T cell depletion) transplants (n = 1297). As for D/R HLA-E matching, we did not identify any significant effect on any of the clinical outcome endpoints. In conclusion, this is the largest study to date reporting an improvement of DFS and TRM after matched unrelated HSCT by avoidance of HLA-E*01:03 homozygous donors in patients transplanted with T cell replete grafts for acute leukemia.

Fiber reinforced cementitious matrix (FRCM) composites represent an effective alternative to fiber reinforced polymers (FRP) to strengthen existing concrete and masonry structures . When a single layer of fiber textile is employed, FRCMs generally failed due to debonding at the matrix-fiber interface and the presence of friction/interlocking residual stresses was observed for some composites. Therefore, the study of the stress-transfer mechanism is a fundamental topic to understand the behavior of FRCM composites and provide reliable design procedures. In this paper, the bond behavior of FRCM composites is studied by an analytical approach based on the use of an elasto-brittle bond-slip law that accounts for the possible presence of friction stresses. A stress and an energy criterion are put forward to describe the stress-transfer mechanism distinguishing between the bond and friction contributions. Finally, a comparison between the results of the analytical approach and corresponding experimental load responses is provided, showing that the methodology proposed is a fast and easy tool to estimate the bond behavior of FRCM composites.

Background Despite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT. Patients/methods We systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords ‘allogeneic’ and ‘myeloma’. Results A total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56–84%), 62 (95% CI 53–71%), 52 (95% CI 44–61%), and 46 (95% CI 40–52%), respectively; for progression-free survival were 51 (95% CI 38–64%), 40 (95% CI 32–48%), 34 (95% CI 27–41%), and 27 (95% CI 23–31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14–21%), 21 (95% CI 17–25%), 20 (95% CI 13–26%), and 27 (95% CI 21–33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5–18%). The incidences of grades II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30–37%) and 51 (95% CI 46–56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45–55%) and 51 (95% CI 45–57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk. Conclusion Due to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options. Electronic supplementary material The online version of this article (10.1186/s12935-018-0553-8) contains supplementary material, which is available to authorized users.

Software ecosystems (SECO) have been related to products or to a community of developers around a product. The SECO concept can also be applied to describe regional software ecosystems in which different software companies collaborate in a specific market based on a set of concrete technologies and using a set of capabilities. This paper details a regional SECO concept and a method based on regional endogenous capabilities and country needs to define a SECO strategy. Traditional strategy definition approaches are top-down, whereas this approach is a blended approach that merges bottom-up based on current regional capabilities and top-down based on market and technology trends. This paper presents a large case study performed in 6 regions of Colombia. We conducted 49 interviews and 16 workshops in which 654 attendees participated, and we developed the Colombian ICT national strategic plan based on this approach.

The paper presents experiments involving punching of RC slabs strengthened using externally bonded carbon fiber reinforced polymer (CFRP) sheet and textile reinforced mortar (TRM). Twelve RC slab specimens of two concrete grades (39.9 and 63.2 MPa) and employing two strengthening schemes (CFRP and TRM) were tested. Specimens were supported on two opposite edges. Experimental load-displacement variations show two peak loads in strengthened slabs and one peak followed by a plateau in control. Second peak or the plateau corresponds to the combined action of aggregate interlock and the dowel action of back face rebars and strengthening layers. The dowel action of back face rebars and strengthening layers had no role in ultimate punching load (i.e. first peak). Strengthened slabs showed 9-18% increase in ultimate punching load (i.e. first peak) whereas there was significant increase in the second peak load (190-276% for CFRP; 55-136% for TRM) and energy absorption (~66% for CFRP and 22-56% for TRM). An analytical model was also developed for predicting the punching shear strength (first and second peaks) of strengthened slabs showing good comparison with experiments.

Developing suitable tools to assess the actual structural performance and designing and executing interventions to improve that performance is a key issue in the field of conservation and enhanceme...

Inorganic-matrix composite materials can be effectively employed to strengthen and retrofit existing reinforced concrete and masonry structures. These composite materials comprise high-strength fiber textiles embedded within inorganic matrices. Different textile layouts and types of matrix and fibers can be employed resulting in a multitude of different composite materials and mechanical behavior thereof. As in most composite materials, the mechanical characterization of the single constituents (matrix and fiber) does not provide indications on the behavior of the composite material. Therefore, the mechanical characterization of the entire composite material is of fundamental importance to understand the interaction (i.e. composite action) between the fiber textile and the embedding matrix. Although different tensile test set-ups were proposed in the literature, a shared standard testing method for the mechanical characterization of inorganic-matrix composites is not yet available. In this paper, the mechanical properties of four different inorganic-matrix composites comprising carbon, glass, basalt, and steel fibers embedded within cement- and lime-based matrices are investigated using two different tensile test set-ups. Analog LVDTs and digital image correlation (DIC) measurements are employed to study the specimen longitudinal strain behavior. Two criteria to assess the reliability of results of tensile tests are proposed. Comparison between results described in this paper shows the strong influence of the test set-up on the tensile behavior of inorganic-matrix composites and helps to shed light on the reliability of the mechanical parameters obtained.

The flexural behaviour of RC beams strengthened with TRM and FRP composites was experimentally investigated and compared both at ambient and high temperatures. The investigated parameters were: (a) the strengthening material, namely TRM versus FRP, (b) the number of strengthening layers, (c) the textile surface condition (dry and coated), (d) the textile material (carbon, basalt or glass fibres) and (e) the end-anchorage of the flexural reinforcement. A total of 23 half-scale beams were constructed, strengthened in flexure and tested to assess these parameters and the effectiveness of the TRM versus FRP at high temperatures. TRM exhibited excellent performance as strengthening material in increasing the flexural capacity at high temperature; in fact, TRM maintained an average effectiveness of 55%, compared to its effectiveness at ambient temperature, contrary to FRP which totally lost its effectiveness when subjected to high temperature. In specific, from the high temperature test it was found that by increasing the number of layers, the TRM effectiveness was considerably enhanced and the failure mode was altered; coating enhanced the TRM effectiveness; and the end-anchorage at high temperature improved significantly the FRP and marginally the TRM effectiveness. Finally, the formula proposed by the Fib Model Code 2010 was used to predict the mean debonding stress in the TRM reinforcement, and using the experimental results obtained in this study, a reduction factor to account for the effect of high temperature on the flexural strengthening with TRM was proposed.

The aim of this paper is to compare the flexural performance of reinforced concrete (RC) beams strengthened with textile-reinforced mortar (TRM) and fibre-reinforced polymers (FRP). The investigated parameters included the strengthening material, namely TRM or FRP; the number of TRM/FRP layers; the textile surface condition (coated and uncoated); the textile fibre material (carbon, coated basalt or glass fibres); and the end-anchorage system of the external reinforcement. Thirteen RC beams were fabricated, strengthened and tested in four-point bending. One beam served as control specimen, seven beams strengthened with TRM, and five with FRP. It was mainly found that: (a) TRM was generally inferior to FRP in enhancing the flexural capacity of RC beams, with the effectiveness ratio between the two systems varying from 0.46 to 0.80, depending on the parameters examined, (b) by tripling the number of TRM layers (from one to three), the TRM versus FRP effectiveness ratio was almost doubled, (c) providing coating to the dry textile enhanced the TRM effectiveness and altered the failure mode; (d) different textile materials, having approximately same axial stiffness, resulted in different flexural capacity increases; and (e) providing end-anchorage had a limited effect on the performance of TRM-retrofitted beams. Finally, a simple formula proposed by fib Model Code 2010 for FRP reinforcement was used to predict the mean debonding stress developed in the TRM reinforcement. It was found that this formula is in a good agreement with the average stress calculated based on the experimental results when failure was similar to FRP-strengthened beams.

In the last decades, there are many reports on the use of composites as reinforcement of structural elements under compression, especially regarding the confinement of concrete structures, but works on stone or masonry columns are limited. Initially, FRP jackets were used because their high structural performance. However, they present some drawbacks like aesthetics or water impermeability, which can affect their applicability in historical constructions made in stone. Recently, FRCM appeared as an alternative with better compatibility with masonry structures. In the present study, a comparison between different composite materials to confine masonry specimens was made. FRPs with carbon or glass fibers and epoxy matrix, and FRCM with basalt or glass fiber mesh in a cementitious matrix were used to confine masonry, made in calcarenite cylindrical pieces and lime mortar. Strength and ductility gains under compressive loads were measured, and compared to the recommendations of different guidelines. Unidirectional FRPs were the optimal solution from a strengthening point of view. On the other hand, FRCM confinement offered more ductility than unreinforced masonry, but showed a softening behavior. Finally, regarding the studied design codes, the specific parameters included for masonry structures seemed enough to obtain accurate predictions of the compressive strength increase due to the confinement with the tested composites. This research and the APC were funded by Spanish Ministry of Economy and Competitiveness, grant number BIA2015-69952-R and Spanish Ministry of Science, Innovation and Universities, grant number RTI2018-101148-B-I00.

Students, their families, employers and the government want the assurance that students will get “good quality” education. The question is: what does “good quality education” mean? This paper seeks to provide the answer as well as some concrete criteria and proposals to improve the objectives and quality of the education systems. We argue in this study that the quality of higher education and student satisfaction is a cumulative construct, summing various facets and variables of the educational institution, such as technical, functional, infrastructure, interaction and atmosphere variables. In this research we describe a study involving a new instrument, i.e. the 5Qs model and a new method which assures the reasonable level of relevance, validity and reliability, while being explicitly change-oriented. The main goal of the empirical part of this study is not to evaluate the performance of the staff or to analyze the student assessment or satisfaction, rather to test the new 5Qs model. The use of the 5Q dimensions provides both a structure for designing a higher education quality measurement instrument and a framework for prioritizing results and findings.

Allogeneic hematopoietic cell transplantation (HCT), but not autologous HCT, can provide long-term remission in some patients with adult T cell leukemia-lymphoma (ATL). We retrospectively analyzed the effects of acute graft-versus-host disease (GVHD) among the 616 patients with ATL who survived at least 30 days after allogeneic HCT with other than cord blood grafts. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated an association between grade I-II acute GVHD and favorable overall survival (OS) (hazard ratio [HR], 0.634; 95% confidence interval [CI], 0.477 to 0.843), whereas grade III-IV acute GVHD showed a trend toward unfavorable OS (HR, 1.380; 95% CI, 0.988 to 1.927) compared with nonacute GVHD. In subsequent multivariate analyses of patients who survived at least 100 days after HCT (n = 431), the presence of limited chronic GVHD showed a trend toward favorable OS (HR, 0.597; 95% CI, 0.354 to 1.007), and extensive chronic GVHD had a significant effect on OS (HR, 0.585; 95% CI, 0.389 to 0.880). There were no significant interactions between myeloablative conditioning or reduced-intensity conditioning with OS even when acute GVHD was absent or present at grade I-II or grade III-IV or when chronic GVHD was absent, limited, or extensive. This study demonstrates the actual existence of graft-versus-ATL effects in patients with ATL regardless of whether myeloablative conditioning or reduced-intensity conditioning is used.

An increasing interest and application is nowadays found for composite systems in construction and rehabilitation industry. The consensus on fibre reinforced composite systems was mainly based on high tensile strength, light weight, relative ease of installation, and resistance to corrosion. However, some drawbacks related to the epoxy (hence, organic) matrices of Fiber-Reinforced Polymers (FRP) have been solved by inorganic ones yielding to novel fibre reinforced composites. In these materials the composite action is mainly achieved through mechanical interlock between the matrix (e.g. a cement- or a lime based mortar or a geopolymer with the option of chopped fibres and/or low-content polymer addition) and the mesh-like fibrous structure (a textile) that allows the mortar to protrude through the grid's openings. Aiming at the investigation of the mechanical properties and the development of testing procedures for this new family of materials (termed herein as Fabric-Reinforced Cementitious Matrix (FRCM)) the present paper presents the results of an extensive experimental program on different combinations of basalt fibre textiles and inorganic matrices organized by RILEM TC 250-CSM (Composites for the Sustainable strengthening of Masonry) involving ten European laboratories. The tests involve more than 100 specimens: half are tensile tests and the other half are bond tests carried out on prisms made of clay bricks, on three different basalt-based FRCM configurations comprising readily available commercial systems provided by different producers. The scope of this work is aimed not only at presenting a comparative performance assessment of different Basalt FRCM systems, but also at providing meaningful criteria to reliably design and analyse retrofit applications. The relevant round robin test program provides valuable data generated during the experimental activity and statistical analysis thereof; then, based on the various testing approaches employed, the advantages/drawbacks of certain testing factors are sum, The authors would like to thank the companies which supported the whole experimental project: Fyfe Europe S.A., Athens (Greece), G&P INTECH s.r.l. Altavilla Vicentina (Vicenza, Italy), Mapei S.p.A. Milano (Italy), for providing composite materials; and SanMarco-Terreal Italia, Noale (Venice, Italy) for providing the bricks., info:eu-repo/semantics/publishedVersion

Rammed earth constructions are widely found worldwide, but they are endangered by their recognised high seismic vulnerability. As compatible and affordable reinforcement approaches are important requirements for these constructions, a strengthening solution based on low cost textile reinforced mortars (LC-TRM) is proposed here, within the framework of a large research project. This paper presents the results of an experimental program aimed at characterising low cost meshes available in the market (glass fibre, plastic, metallic and nylon) and at assessing possible mortars (unstabilised earth, stabilised earth, commercial earth and cement-based) capable of integrating the LC-TRM strengthening system. In general, the results obtained seem to indicate that the glass fibre meshes and the earth mortar are good options., This work was partly financed by FEDER funds through the Competitivity Factors Operational Programme - COMPETE and by national funds through FCT – Foundation for Science and Technology within the scope of projects POCI-01-0145-FEDER-007633 and POCI-01-0145FEDER-016737 (PTDC/ECM-EST/2777/2014). The support from grant SFRH/BPD/97082/2013 is also acknowledged., info:eu-repo/semantics/publishedVersion

This paper presents the results of the mechanical characterization of composite materials comprising high strength textiles embedded in inorganic matrices. These materials are commonly termed Textile Reinforced Mortars (TRM) or, when comprising cementitious matrices, Fabric-Reinforced Cementitious Matrix (FRCM – despite the fact that this term is often extended to composites with cement-free matrices). Different types of fibers were employed, namely carbon, glass, and basalt, as well as steel cords, which were embedded in lime- or cement-based matrices. Results of tensile tests on single fiber yarns and composite prismatic specimens with a rectangular cross-section are shown and discussed. The effect of fiber coating and stitch-bonded joints between warp and weft yarns on the tensile behavior observed is studied. The results obtained help to shed light on the different parameters that affect tensile testing of inorganic-matrix composites contributing to the appropriate mechanical characterization of these materials.

Rammed earth constructions represent a valuable cultural heritage of vernacular architecture, whose significance has acquired even more importance in the last years with the renovated interest for this sustainable building technique. The aim of this work is to develop a FEM model typologically representative of a Portuguese vernacular rammed earth construction in order to characterize numerically its seismic performance and raise awareness about the level of improvement introduced by two compatible strengthening techniques: textile reinforced mortar (TRM) and a ring beam applied at the top of the walls., This research work was partly financed by FEDER funds through the Competitivity Factors Operational Programme (COMPETE) and by Portuguese national funds through FCT(Foundation for Science and Technology) within the scope of projects POCI-01-0145-FEDER-007633 and POCI-01-0145-FEDER-016737 (PTDC/ECM-EST/2777/2014). The support from grant SFRH/BPD/97082/2013 is also gratefully acknowledged.

Key Engineering Materials, vol. 747., Tensile Reinforced Mortars (TRMs) are promising composites that address the compatibility demands required for strengthening of masonry and historical constructions. Although many recent studies have been devoted to the use of these materials for strengthening purposes, several issues such as efficiency for improving the structural performance are clearly open. The aim of this paper is to numerically investigate the effectiveness of TRM systems on the in-plane and out-of-plane response of masonry walls. Numerical models are adopted to describe the nonlinear behaviour and the failure mechanisms of unreinforced and strengthened walls. It is shown that the implementation of TRM layers improve largely the performance of the masonry walls both in terms of strength and displacement capacity., (undefined), info:eu-repo/semantics/publishedVersion

Several studies have shown that chronic GVHD (cGVHD) is more frequent in patients receiving transplants from PBSC than in those receiving BM. In the setting of PBSC-unrelated transplants, the addition of anti-T-cell globulin (ATG) has shown a significant decrease in incidence/severity of cGVHD, without an increase in relapses or infections. However, no prospective data are yet available in the sibling setting. We retrospectively analyzed the effects of intensification of standard GVHD prophylaxis (CsA+MTX) by the addition of low-dose ATG in 245 patients receiving a transplant from HLA-identical sibling. From 1996 to 2001, patients received PBSC as the preferred source (group 2), and then ATG was added before transplant (group 3) because of a high cGVHD rate. Patients receiving BM in the same time period were analyzed as a control group (group 1). The incidence of grade III-IV acute GVHD and cGVHD was not significantly different in the three groups, but extensive cGVHD was highest in group 2 (38%) compared with group 3 (21%) or group 1 (28%; P=0.03). OS, TRM and time to relapse/progression were similar in the three groups. Our analysis shows that adding ATG to PBSC sibling allogeneic transplants can lower cGVHD, without an increase of relapse. Further prospective studies are needed to confirm these findings.

Pharmacological targeting of memory cells is an attractive treatment strategy in various autoimmune diseases, such as psoriasis and rheumatoid arthritis. Multiple sclerosis is the most common inflammatory disorder of the central nervous system, characterized by focal immune cell infiltration, activation of microglia and astrocytes, along with progressive damage to myelin sheaths, axons, and neurons. The current review begins with the identification of memory cell types in the previous literature and a recent description of the modulation of these cell types in T, B, and resident memory cells in the presence of different clinically approved multiple sclerosis drugs. Overall, this review paper tries to determine the potential of memory cells to act as a target for the current or newly-developed drugs.

The performance of various composite materials applied to strengthen hollow masonry panels under out-of-plane actions is compared here. The strengthening solutions belong to three reinforcement Externally Bonded (EB) wet lay-up systems: (i) bidirectional composite meshes applied with inorganic matrices, i.e., Textile Reinforced Mortars (TRM); unidirectional composite textiles applied with (ii) inorganic matrices, i.e., Steel Reinforced Grouts (SRG), or (iii) organic (epoxy) matrices, i.e., Fibre Reinforced Polymers (FRP), Steel Reinforced Polymers (SRP) and Natural FRPs. Carbon FRP, flax and hemp NFRP, and basalt and glass-based TRM were examined. As inorganic matrix, a cement-based mortar was used for TRMs; in the case of SRGs, comparisons with a magnesia-based matrix were also carried out. Twenty-seven specimens were subjected to simplified four-point monotonic bending tests, aimed at reproducing in the laboratory the failure condition of infill masonry walls under out-of-plane actions. The results are compared in terms of failure mode and mechanical improvement, and provide an analytical evaluation of moment–curvature behaviour according to bilinear laws.

A research, made in collaboration with Politecnico di Milano and University of Padua, has started with the aim of evaluating the influence of aggressive environmental conditions (moisture, temperature and soluble salts presence) on the bond between FRP/TRM and masonry substrates. Experimental tests were carried out on site on full-scale masonry models, built in open air in a polluted area in the hinterland of Milan, naturally subjected to thermal, R.H. and UV cycles; furthermore, they were artificially subjected to capillary rise of a solution of water and Sodium Sulphate so as to create salt crystallization cycles. On two different masonry substrates, representing a simple historic masonry structure, made either by soft-mud bricks or sandstone units with lime mortar, various FRP and TRM strips were vertically applied in order to evaluate the bond at three heights. TRM were applied with two different premixed inorganic matrices (pozzolanic lime based mortar and cement polymer modified mortar) and FRP with an organic matrix (epoxy resin). The fibres used were unidirectional carbon and glass fabrics for FRP, and a bidirectional carbon net for TRM. The bond was evaluated by means of pull-off tests and the first results, herein presented, show the influence of moisture presence and of salt crystallization cycles on the different used matrices.

This report focuses on multi-channel transmit/receive modules (TRM) which are part of AESAs. The principles of TRM design are reviewed herein, as well as specifics of transmission and receipt modes.

The fuzzy front-end plays a most crucial part in new product development (NPD), leading to the success of product development and product launch in the market. This study proposes a novel method, TTRI_MP, by combining Crawford and Di Benedetto’s model and Cooper’s model, to strengthen the management of the fuzzy front-end. The proposed method comprises four stages: market exploration and technology forecasting, idea generation and segmentation, portfolio analysis and technology roadmapping (TRM). In the first stage, SWOT was utilized to identify the key strategic areas, and the technology readiness level (TRL) was adopted to position the level of developed technologies. In the second stage, the business concepts were required to go through the viability test and customers, collaborators, competitors and company (4C). In the third stage, the Strategic Position Analysis (SPAN) and Financial Analysis (FAN) developed by IBM were employed in the portfolio analysis to screen out potential NPD projects. In the last stage, the selected NPD projects were linked with their functions and technologies in the TRM chart. The method was successfully implemented by a research team working on a flexible fabric supercapacitor at the Taiwan Textile Research Institute (TTRI).

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. Our objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute graft vs host disease (GVHD), treatment-related mortality (TRM) and survival after HCT. The preparative regimen consisted of cyclophosphamide 50 mg/kg/day i.v. day −6; plus fludarabine 30-40 mg/m2/day i.v. on days −6 to −2 and TBI 200 cGy on day −1. F-ara-A pharmacokinetics were performed with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A AUC (0-∞) was 5.0 ug*hr/mL (2.0-11.0), clearance 15.3 L/hour (6.2-36.6), Cmin 55 ng/mL (17-166), and concentration on dayzero 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced overall survival. Patients with an AUC(0-∞) greater than 6.5 ug*hr/mL had 4.56 greater risk of TRM and significantly lower survival. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT.