Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin treatment has been consistently reported in the current literature. Inner ear hair cells seem to have intrinsic characteristics that make them susceptible to direct exposure to cisplatin. The existing literature suggests, however, that cisplatin might have different patterns of drug trafficking across the blood-labyrinth-barrier, or different degrees of cisplatin uptake to the hair cells in the cochlear and vestibular compartments. This review proposes an explanation for the preferential cochleotoxicity of cisplatin based on current evidence as well as the anatomy and physiology of the inner ear. The endocochlear potential, generated by the stria vascularis, acting as the driving force for hair cell mechanoelectrical transduction might also augment cisplatin entry into cochlear hair cells. Better understanding of the stria vascularis might shed new light on cochleotoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin associated ototoxicity. Cisplatin (platinum-based chemotherapy), is the mainstay treatment for curative care of various cancers . OtotoxiThis review gleans the current evidence of cisplatin-induced ototoxicity and the mechanisms in the light of existing literature and data. Possible mechanisms are suggested as to why cisplatin predominantly affects the cochlea while relatively sparing the vestibular counterpart based on available preclinical and clinical data.+) and high sodium (Na+) concentrations, and the endolymph containing high K+ and low Na+ concentrations. Specific cells and structures are required to maintain the electrolyte concentrations and homeostasis of the inner ear fluid  are needed to maintain a very high K+ concentration and recycling of electrolytes into endolymph (The cochlear (responsible for hearing) and vestibular  parts of the inner ear have a very close anatomical relationship, and share a common source of blood and fluid supplies . These tar fluid . Active ndolymph . Vestibu+ equilibrium diffusion potential, in the cochlea across the apical membranes of the intermediate cells in the stria vascularis  influx during sensory transduction and subsequently enhance the neurotransmission of sounds  adducts, leading to DNA denaturation which blocks cell division processes . Anothervia the mechanoelectrical transduction channel pore, transmembrane channel-like protein 1 (TMC1), or by passive diffusion at apical membranes  which has been demonstrated for aminoglycoside antibiotics .Hearing loss to variable degrees has been reported in 40–80% of patients treated with cisplatin depending on patient characteristics, drug dosage, and differences in tools and grading system . The typThe phenomenon of cochlear dead regions involves loss of inner hair cells whilst outer hair cells are intact, can lead to difficulty understanding speech in noisy environments. This situation has been reported in a small cohort of adults who had undergone cisplatin chemotherapy  but thisThe clinical evidence regarding the potential of cisplatin vestibulotoxicity is limited in the published literature. The reported rate of abnormal caloric or rotational tests associated with cisplatin varied considerably from 0 to 50% . Some li2). The normal vHIT results indicate that the vestibulo-ocular reflex (VOR) activity is unaffected after cisplatin treatment. No evidence of corrective saccades was found, indicating that there was no subclinical vestibular impairment. The vHIT has the major advantage of specificity but at the expense of sensitivity  results . On the sitivity . This mesitivity , and versitivity  in the aTo date, there is no study of patients treated with cisplatin that incorporates the caloric test, rotational chair test, and vHIT to evaluate the VOR across different frequency ranges in the same setting. In case of aminoglycoside ototoxicity, vestibular function in low-mid frequency ranges was selectively affected but high frequency function was spared . It is tIn general, cisplatin affects both cochlear structure and function, yet has a much lower likelihood to do so in the vestibular organ. One plausible explanation is that cisplatin does affect vestibular end organs, yet only a relatively low occurrence of vestibular symptoms is reported due to bilateral effects, insidious onset, and effective compensation mechanisms . HoweverThe observations regarding morphological, biochemical, and functional changes after cisplatin exposure might shed some lights on the mechanisms of ototoxicity. The distinct patterns of hair cell loss after topical and systemic cisplatin administration could be explained by different drug trafficking across the blood-labyrinth-barrier or different degrees of cisplatin entry into sensory hair cells in the cochlear and vestibular compartments. Different endolymphatic potential status and supporting structures of the cochlear and the vestibular labyrinth might explain this phenomenon. The high electrochemical driving force of the endocochlear potential at 80–100 mV might strongly drive cisplatin, provided it is in its aquated, positively charged forms, to enter the hair cells . This isex vivo, organotypic cultures of the cochlea were exposed to cisplatin. Also, they found a significant lower level of the antioxidant glutathione in basal outer hair cells compared with apical outer hair cells, suggesting that basal outer hair cells are more vulnerable to free-radical damage than apical ones. On the other hand, the preferential frequency of cisplatin vestibulotoxicity is unclear. It is possible that vestibular impairment is not homogenous across the frequency range. Unlike the cochlea, which has a well-structured tonotopic arrangement, the motion- and vibration-sensitive arrangement of the vestibular organs is not well structured.Cisplatin initially damages the outer hair cells at the basal turn of the cochlea, resulting in hearing loss at higher frequencies. There are at least two possible explanations for the sensitivity to cochleotoxic damage of cisplatin along the cochlear spiral. The first one relates to different drug distribution along the base-to-apex in the cochlea that facilitates greater cisplatin uptake in the basal part. Cisplatin signal intensity was highest in the cochlear base, and it generally decreased with progression toward the apex . The con2+ metabolism, which is not necessarily correlated with hair cell injury. Cisplatin could cause electrochemical alteration of Ca2+ homeostasis in the vestibular compartment rather than hair cell damage (2+ concentration in endolymph induces the release of Ca2+ from otoconia and otoconial detachment from the otolithic membranes. Alternatively, limited physical activities due to general fatigue of cancer patients could also underlie the relatively high rate of BPPV in this sample (A recent finding of the relatively high prevalence of BPPV after cisplatin treatment is of interest in this regard . The patl damage . The reds sample . These oIn general, cisplatin ototoxicity appears to target cochlear structures resulting in hearing loss and/or tinnitus. Definite vestibular dysfunction after cisplatin treatment has not been consistently reported in the current literature. Cisplatin might have different pattern of drug trafficking across the blood-labyrinth-barrier or varying degrees of entry into hair cells in the cochlear and vestibular compartments. The endocochlear potential might also increase uptake of aquated cisplatin into the cochlear hair cells through cation transporters or the mechanoelectrical transduction channels. Although the VOR was generally unaffected, other vestibular effects of cisplatin such as biochemical disruption are possible. Further investigations are warranted for greater insight into the mechanisms of cisplatin trafficking, cellular uptake kinetics, and electrochemical disruptions. Better understanding of the stria vascularis might shed new light on ototoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin-induced ototoxicity.PP wrote, revised, and edited the manuscript. DB wrote, reviewed, revised, and edited the manuscript. CK and PS reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The exosome-mediated response can promote or restrain the diseases by regulating the intracellular pathways, making the exosome become an effective marker for diagnosis and therapeutic control at the single-cell level. However, real-time analysis is hard to be achieved with traditional approaches because the exosomes usually need to be enriched by ultracentrifugation for a measurable signal-to-noise ratio. Recently developed label-free single-molecule imaging approaches may become an real-time quantitative tool for the analysis of single exosomes and related secretion behaviors of single living cells owing to their extreme sensitivity. Exosomes are released by various mammalian cells, and they can be captured by distant cells, where they can alter the biological response of recipient cells. Intercellular communications via exosomes are involved in many physiological derangements, such as neurodegeneration, tumor mutations, and inflammatory reactions. The exosomes-mediated response can promote or restrain the diseases by regulating the intracellular pathways, making the exosome become an effective marker for diagnosis and therapeutic control . In addiSingle molecule imaging was firstly developed in the late 1980s by employing the fluorescence emission to shift detection wavelength away from excitation wavelength, and dichroic mirror and optical filter were used to achieve near-zero background for detection of the weak signals from single molecules. Single molecule fluorescence microscopy allows detection and tracking of single proteins, and its feasibility for small exosome detection has been demonstrated owing to its extreme sensitivity (2 or higher) to be within the ~100 nm of the sensor surface, thus allowing the implementation of simultaneous fluorescence imaging for detection most of the cell volume without worry of quick photobleaching. This means that the PSM permits the flexible combination with other optical imaging approaches, thus allowing multiplexed detection of exosome secretion process of single cells.Plasmonic scattering microscopy (PSM), one kind of label free single molecule imaging approach, was recently developed based on the conventional surface plasmon resonance (SPR) system  Zhang e. This inThere are still a few challenges need to be overcome for stable real-time analysis of exosome secretion with PSM. The first challenge is that the cells may release many products during the secretion and label free imaging is sensitive to all objects with the size down to single protein level, so the recognition of target exosomes need to be addressed. A potential solution for this challenge is modifying the sensor surface with antibodies targeting exosome surface markers, such as CD63 and CD81, for recognizing the exosomes specifically . The sec


Over the years, prestressing concrete has become a well-known technique to improve the ultimate and serviceability state of RC members. Besides steel reinforcement, relatively new materials such as carbon fiber reinforced polymers (CFRP) or especially shape memory alloys (SMA) can be used to active strengthening. The main scope of this paper is to compare various prestressing methods using carbon composites and memory steel alloys. A description of SMA, shape memory effect, its utilization for prestressing, and CFRP materials are presented in the paper. Moreover, current state-of-the-art developments in the field of both materials, considering prestressing systems and available anchorage, material behavior, creep and stress relaxation, durability issues, thermal compatibility with concrete, and fire behavior, are described. A general revision of previous studies based on flexural strengthening using both materials is conducted and the selected results of these studies are briefly presented. The behavior of RC beams after strengthening with mentioned techniques is compared and discussed. Selected on-site applications are described to confirm the feasibility and practicality of the strengthening systems. Finally, the main advantages and disadvantages of CFRP and SMA materials for prestressing concrete structures are summarized and further recommendations for the future research are listed. Plenty of existing structures require retrofitting and strengthening. This is most often important due to the deterioration of structures, changes in using their functionality, or increasing design requirements. In the case of concrete structures in Poland, traditional methods of strengthening are still the most popular. These methods of retrofitting  are well known and described by Al-Mahaidi et al. . HoweverStrengthening with prestressed CFRP materials requires a mechanical anchorage that properly transfers prestressing force to the strengthened member to avoid debonding of composite material from the concrete surface. The anchorage systems are highly complex due to additional devices based on the hydraulic jacks, which are used for prestressing the CFRP laminates ,9,10,11.A promising alternative for the prestressing methods of existing concrete members, which substantially reduces these expenses, is prestressing using shape memory alloys (SMA). Several research studies about the most popular nickel-titanium based alloys (NiTiSMA), have been tested for decades and confirmed their capabilities for retrofitting concrete members ,13. HoweThis paper aims to present the current state-of-the-art developments in the topic of flexural strengthening of RC structures with prestressed SMA materials in comparison to that with CFRP. This comparison contains an analysis of materials behavior, available prestressing systems, and previous studies with applications of both memory steel and carbon composite materials. The paper provides a background for further research in this field which can be of significant interest. Shape memory alloys are metallic alloys  that have a unique property which allows them to return to their initial shape after having been permanently deformed. Examples of FeSMA materials are presented in s, (martensite start) and the process finishes at the temperature, Mf, (martensite finish). The reverse transformation (RT) is induced by heating the material (in absence of stresses), begins at temperature known as, As, (austenite start) and has the end at the temperature, Af, (austenite finish) [Change of deformability is called the shape memory effect (SME) and has to be activated by heating . If the  finish) . These p finish) .Depending on the ambient and transformation temperatures profile of the alloy material, different phenomena occur in the material ,20. It cs, the reverse transformation begins. As strain-stress curves for martensite and austenite are different, a change of stiffness takes place. An increase in the stiffness of the alloy causes the strain decreases against a constant force . The reverse transformation occurs automatically after unloading. This phenomenon is called superelasticity or pseudoelasticity and it exhibits some stress-strain hysteresis , as showf. This phenomenon is called the one-way shape memory effect or pseudoplasticity [max, tensile stress develops in the material. The stress obtained by cooling the specimen down is referred to as “recovery stress”  are composite materials composed of at least two components, namely fibers and a polymer matrix. The matrix performs the role of binder, distributes the uniform load, and protects the fibers against environmental effects . The fibUnidirectional pultruded laminates (strips)—Sheet (with fibers in one direction) or fabrics (fibers are arranged in at least two directions) that are usually impregnated in-situ;Rods of bars that are made by pultrusion;Profiles —The properties of CFRPs depend on the volume of each component and the orientation of fibers. CFRPs are available for strengthening of civil engineering structures in the form of ,35:UnidiThe first application of CFRP materials was in the United States at the California Department of Transportation, Caltrans . ApplicaMost research and field applications on the flexural strengthening of RC members were carried out on simply supported beams and slabs strengthened on the bottom surface of the RC members without additional anchorage in the support region.The existing research on reinforced concrete members flexurally strengthened with FRP materials can fail in several different ways, which are completely different in comparison with original RC members. There is a wide literature referring to classification of the failure modes published for the last two decades. The most common classification based on test results of the existing research was presented in . Eight cThe most common failure mode is debonding of the FRP laminate from the concrete surface which may proceed as intermediate crack induced interfacial debonding (ICD) initiates at the flexural/flexural-shear cracks in the highest bending moment region f and proCritical diagonal crack (CDC) debonding occurs after the formation of a major shear crack intersecting the plate near its end and develops along with the laminate-concrete interface to the plate end b;Concrete cover separation (CCS) c;Plate end interfacial debonding (PEI) d.When debonding occurs at or near the end of a laminate it may proceed in three different ways:Two additional failure modes refer to the FRP rupture and concrete crushing. However, the second one is possible only for the RC members of low concrete strength and high reinforcement ratio.The effectiveness of the flexural strengthening depends on several factors including FRP type; axial stiffness and the number of CFRP layers; a distance of the CFRP end from the support; the existing longitudinal and shear steel reinforcement ratio; and bending moment distribution. Although EBR CFRPs increase the load-bearing capacity of an RC member, they do not significantly change the cracking load and deflections under the service loads. To gain the greatest advantage of the EBR technique, CFRP prestressing has been proposed to improve the serviceability of strengthened structures in order to reduce crack widths effectively, to relieve stress in the internal reinforcement, to enable control the crack distribution, limit deflection, and to increase the stiffness and the load capacity of RC members.This section is focused on a comparison of CFRP and SMA behavior and techniques of their applications to the strengthening of RC structures. The important parameters considered in this analysis contain tensile strength, Young’s modulus, creep and relaxation, thermal compatibility, durability, behavior at elevated temperatures, prestressing procedure, prestressing force, and anchorage systems.Memory steel based on iron has reasonable production cost, higher elastic modulus, and lower activation temperature in comparison with other types of SMA materials . FeSMA mExternally applied reinforcement (EAR) which include both externally bonded reinforcement (EBR) and unbonded reinforcement (without adhesive between composite and concrete); the unbonded reinforcement system is much less popular, but the applications can be found in ,54;Near-surface mounted reinforcement (NSMR) ,59,60,61Externally post-tensioned (EPT).The state-of-the-art strengthening with prestressed FRP materials was published in ,51,52,53In the EAR technique, CFRP reinforcement is in most cases prestressed to reduce existing deflections and to extend the flexural capacity of the existing concrete structures (direct prestressing method ). CFRP pIn most cases, the MA systems are based on anchor plates. A direct prestressing system consists of the passive anchorage (dead end), while the second end is the active one ,72 whichReinforced concrete beams strengthened with prestressed CFRP laminates show three groups of failure modes: under-reinforced RC members failed due to FRP rupture (R); over-reinforced RC members with composite reinforcement applied excessively, resulting in concrete crushing (CC). However, this failure mode is possible only for the RC members characterized by low concrete strength and high reinforcement ratio; intermediate crack induced by interfacial debonding (ICD), which initiates at the flexural/flexural-shear cracks in the highest bending moment region and propagates by gradual debonding of the laminate from the flexural crack to the FRP end and the group of RC members with the reinforcement not anchored sufficiently, in which leads debonding of FRP ends (plate end debonding (PE), concrete cover separation (CCS), anchorage failure (AF)) published in ,76,77,78The parameters affecting strengthening efficiency with externally bonded FRP prestressed materials contain type of FRP material ; FRP stiffness; existing flexural tensile reinforcement ratio; existing shear reinforcement ratio; stiffness of the strengthened RC member ; the size of the strengthened RC member; type of strengthening system  or partially efficient (FRP sliding from the anchored system) and preloading level.The flexural strengthening of RC members strengthened with pretensioned NSM FRP stirps or bars confirms the much higher efficiency of this technique compared to the passive strengthening. The main effect of pretensioning is based on the higher utilization of the tensile strength of the FRP materials, which contributes to the higher load-bearing capacity under service and ultimate load ,56,57. TFor externally applied strips, the direct fastening system is used . This meThe NSM strips or bars can be inserted into the concrete grooves which are filled with cement-based grout ,24,81. TThe NSM bars can be also embedded in the shotcrete layer ,24.The prestressing procedure for all types of SMA reinforcement is quite similar and it does not require using the hydraulic jacks. In the beginning, the SMA materials are initially prestrained at room temperature, and then the reinforcement (with permanent deformation) is applied and fixed to the concrete surface and the activation of the alloy is conducted by heating to the required temperature. The heat supply can be provided by infrared heating, electrical resistive heating  or usingFeSMA materials exhibit a similar stress-strain response as steel. The memory steel properties are affected by the alloy composite and the thermomechanical treatment during the production process . In geneact, than for the material in elastic state, Einit, see The initial elastic modulus of FeSMA is similar to low modulus CFRP and is lower than steel and the high modulus CFRP strips. It should be mentioned that Young’s modulus of the alloy depends on its actual state, which is about two times lower for the material after activation, EThe creep behavior of FRP materials was investigated by Goertzen et al.  in the tA mount of tests referring to FeSMA relaxation has been carried out over the last years published in ,94,95,96The prestressing force in the SMA technique depends on the recovery stress of the alloy which is obtained after activation. It highly depends on the alloy composition, thermo-mechanical training, level of prestraining, and activation temperature. Based on data from research conducted by Cladera et al. , it has The prestressing level in CFRPs should be at least 25% and does not exceed 65% of the ultimate strength  see Sec. PrestreDue to the non-metallic nature of CFRPs, these materials are fully corrosion-resistant. This is why environment exposure does not affect the decrease in the tensile CFRP strength ,101.corr), the higher the corrosion resistance of the material in the tested solution. Lee et al. [3 + 5 mM Na2CO3) and with chloride (15 mM NaHCO3 + 5 mM Na2CO3 + 2.8 M NaCl) was conducted by Lee et al. [The corrosion resistance of memory steel has been investigated for various iron-based SMAs in ,109,110.e et al.  and Joo e et al. . Dias ete et al. . As it ce et al. ,108, seee et al.  and Lante et al.  or a smae et al. . Neverthe et al. .−6 K−1 [−6 K−1. The current study has demonstrated that the CTE of FeSMA is in the range of 14–16 × 10−6 K−1 that is closed to other austenitic steel materials [In the case of strengthening applications, proper thermal compatibility between the reinforced material and concrete is of great importance. A significant difference in the thermal expansion coefficients (CTE) imposes the additional stresses in the strengthened element that causes a decrease in the strengthening efficiency . CTE of −6 K−1  and the aterials ,95. The aterials  confirmeaterials  as a resaterials ,115,116.aterials , the lonThe complex study on the structural fire behavior of the prestressed FeSMA was carried out by Ghafoori et al. . The serThe fire behavior of CFRP materials applied for strengthening concrete structures was investigated by Bisby et al.  and FirmA limited number of research studies containing a comparison of flexural strengthening using CFRP and FeSMA materials have been conducted so far. The experiments and computational analysis based on literature ,130,131 Analysis of previous studies (mentioned in the above tables) revealed that different failure modes are exhibited for RC beams strengthened with FeSMA and CFRP materials. The majority of FeSMA beams failed due to concrete crushing after yielding steel (as unstrengthened reference beams) which is connected with their low longitudinal steel reinforcement ratio. In two prestressed beams , one of Selected results from the previous studies are presented in To highlight the better ductility of the FeSMA strengthened beams compared to that strengthened with the CFRP reinforcement, the ductility index was introduced in Michels et al.  comparedFive RC beams strengthened with NSM reinforcements and one reference beam without strengthening were analyzed by Shahverdi et al. in . The beaA study by Raad and Parvin  presentsA numerical comparison of RC beams strengthened with the NSM techniques was conducted in . One refThe first flexural strengthening strips of real structure with prestressed FeSMA happened in 2017 in Villigen, Switzerland ,79. The Another possibility of activation FeSMA strips is infrared heating, which was used during strengthening a slab in Arrau, Switzerland . A new cModernization of reinforced concrete bridge in Komańcza, Poland was required due to its deterioration and narrow roadway ,44. The The NSM technique was used to strengthen a four-span bridge in Gyeonggi-do, South Korea . The briThe strengthening of concrete structures with prestressed CFRP and SMA materials is significantly efficient in serviceability states, including higher cracking load and reduced deflections. The effectiveness of flexural strengthening was confirmed both in laboratory tests and practical implementations.Prestressing using SMAs can be an interesting alternative to prestressing with CFRP materials, especially due to the future price reduction of SMAs.SMA materials can be used as prestressed near surface mounted or externally applied reinforcement. In both cases, they are much easier to apply anchors and activate SMA compared to CFRP materials, which usually require specialized equipment. The FeSMAs are activated by heating to the temperature, which is usually in the range of 130–200 °C.The activation process can be performed using different methods: resistive heating, infrared heating or heating using a gas burner. The prestressing level may be affected by the activation method, however further research on this topic is recommended.The prestressing level of SMAs depends on the type of the alloy, activation temperature and the initial prestraining level. In the presented state of the art, the shape recovery stress was in the range of 130–450 MPa, which resulted in 2–4 times lower prestressing forces than by using CFRP reinforcement. Hence, the flexural capacity of the beams strengthened with CFRP bars and strips is higher than SMAs.The most common failure mode for beams strengthened with CFRP reinforcement was CFRP rupture or CFRP delamination, while the beams strengthened with FeSMAs exhibited usually a failure due to concrete crushing after the steel yielding. A proper design of strengthening using CFRP reinforcement is needed to utilize their high tensile strength and to prevent the brittle failure mode.The behavior of SMA is very ductile that allows the RC members to obtain much higher deflections. The ductility index for all beams strengthened with SMA was much higher than for CFRP strengthened beams.Two important factors should be considered during the design of strengthening using prestressed memory steel. In first the elasticity modulus depends on the actual state of the alloy since the initial value is twice higher than the value after activation. The latter is appropriate for design purposes. Secondly, the compressive strains in concrete should be limited to 2–2.5‰ as the SMA reinforcement behaves similarly as the external prestressed unbonded tendon.The thermal compatibility with concrete is much better in the case of SMAs, since they have a slightly higher coefficient of thermal expansion than concrete. As the coefficient of thermal expansion of CFRP is close to 0 or even negative the stress changes occur along with the bonded CFRP reinforcements due to the temperature changes.The memory steel exhibits much better performance compared to CFRP when is subjected to elevated temperatures. Additionally, heating and toxic gases are released due to thermal decompositions of the FRP matrix when exposed to a temperature of 300–400 °C. Hence, it is necessary to provide proper fire protection not only due to the strength degradation but also due to the smoke toxicity.The prestress losses in the RC members strengthened with prestressed CFRP materials occurs in the first 100 h and a further decrease in prestressing is negligible, while the memory steel is affected by long-term creep and stress relaxation. The current studies estimate that the prestress losses due to relaxation are about 15%. However, they might be retrieved by second or multiple activations.The CFRPs are fully corrosion resistant due to their non-metallic structure, while SMAs are susceptible to corrosion and that should be taken into account in long-term durability. Memory steel is especially sensitive to chloride ions, which intensifies the pitting corrosion. Hence, additional corrosion protection should be applied for structures in aggressive environments.On-site tests confirmed the practicality of flexural strengthening using prestressed CFRPs for RC bridge structures under dynamic load conditions.Strengthening with FeSMA materials can be combined with other strengthening techniques  to ensure maximum gains in serviceability and ultimate limit states.In this paper, current state-of-the-art developments in terms of prestressed concrete structures using SMA or CFRP reinforcement is presented. Both materials are compared in terms of the material level considering tensile behavior, durability aspects and effects of elevated temperature. Moreover, the prestressing methods and anchorage systems are briefly described. Additional item concerns previous studies considering both experiments and numerical analysis and summary of CFRP and SMA strengthened RC members. The following conclusion can be drawn:The prestress losses and long-term behavior of SMAs used for prestressing of RC structures.The prestressing losses due to the slippage at anchorages should be analyzed.Developing more precise methods of determining prestressing level in memory steel after its application to RC structure.Effects of different heating methods on the prestressing level in SMA materials.The possibility of multiple activations should be developed.The behavior of SMA in chemical environments considering effects on recovery stress or bonding behavior should be investigated in more detail.Feasibility of SMA materials for flexural strengthening of RC structures under dynamic load conditions.Effectiveness of corrosion protection applied to SMA materials.Design guidelines for prestressing with SMA should be organized.Comparison of prestressing techniques using SMA and unbonded CFRP reinforcement with end-anchorages.Future research is necessary to develop the current knowledge of strengthening RC structures with prestressed SMA materials. The following recommendations should be taken into future research:


However, there were no significant relationships between other investigated variables. The results of linear regression have revelated the important role of the overall scores in experience of stress among mothers (explaining 49% of the variability). The mediating role of maternal stress on maternal postpartum bonding was not found. That relationship of maternal postpartum bonding and maternal stress was not moderated through socio-demographic variables. (4) Conclusions: In this study mothers of prematurely born children had a good level of Maternal-Infant bonding. Maternal stress was found to be a predictor of maternal postpartum bonding among the tested variables. Surprisingly, the study results did not show significant relationships between maternal postpartum bonding and maternal mental health (depression and anxiety).(1) Background: There is a continuing discussion concerning the impact of preterm birth on Maternal-Infant bonding with inconsistent results. The large burden of preterm births calls for research to evaluate the impact of it on material psychological outcome in the early postpartum period. Thus, the aim of this study was to evaluate the relationship between maternal postpartum bonding with maternal mental health, socio-demographical factors, and child’s characteristics. (2) Methods: A cross-sectional study design was used. In total, 72 women (a mean age of 31.44 years old) of preterm infants  filled out socio-demographic questionnaires, Postpartum Bonding Questionnaire (PBQ), Edinburgh Postpartum Depression Scale (EPDS), Postpartum Depression Screening Scale (PDSS), Generalized Anxiety Disorder Assessment (GAD-7), and Parental Stress Scale (PSS) 1–3 days post-delivery; (3) Results: The results analyses have shown positive correlations between the overall result of maternal postpartum bonding with stress ( Preterm birth (PTB) is defined as childbirth prior to 37 weeks of pregnancy . PTB is Prematurity may lead to adverse effects on survival as well as medical, physiological, neurophysiological, and intellectual outcomes of a new-born child. Preterm neonates are at increased risk of death from the first 4 weeks of life up to 5 years of age . They haUndeniably, premature delivery of a baby it is an emotionally difficult and stressful event not only for the child and their parents/caregivers but also for relationships in the whole family unit ,14. PTB Maternal-Infant bonding is a concept described as an emotional tie between the mother and her baby . The begThere is a continuing discussion concerning the impact of PTB on Maternal-Infant bonding for the last few decades. However, there is a limited number of studies investigating the PTB impact in the early postpartum period ,33. One The Preterm Birth Priority Setting Partnership in the UK established the top 15 research priorities for preterm birth where bonding played one of the key roles  . As the What is the maternal postpartum bonding score among mothers after a preterm birth?What are scores of stress, anxiety, and depressive symptoms among mothers after a preterm birth?Is postpartum bonding associated with maternal mental health ?Is postpartum bonding associated with a child’s characteristics ?Is postpartum bonding associated with socio-demographical variables ?This paper reports on a study that evaluated the following:The results of this paper present a dataset of a larger longitudinal study concerning the impact of premature childbirth on parental outcomes during the baby’s NICU stay and beyond . Ethics approval was obtained from the Research Ethics Board at the University of Gdansk . Individuals were enrolled at the Neonatology, Gynecology, and Obstetrics Ward of the Medical University of Gdańsk (Poland) by trained assistants who identified mothers who experienced preterm delivery through medical records. Trained assistants were responsible for the first contact with potential participants in the early postpartum period (1–3 days after childbirth) in order to provide them oral and written information about the project, alongside an informed consent form to sign. Participation in the project was voluntary. Each participant had the right to refuse to participate in the study or to withdraw from it at any time for any reason. It is important to mention that in Poland, there is a hospital policy according to which mothers after childbirth stay for 3 days in a hospital; thus, we conducted our study 1–3 days after delivery. Criteria for selecting the subjects were as follows:Inclusion Criteria:Woman in the reproductive age between 18 and 49 years and 11 months. The motivation for the cut-off age limit was due to the role of age in reproductive health  and mental health  ,43,44,45Parents of children born below the 37th week of pregnancy  or above the 37th week of pregnancy (control group),Those that agreed to participate in the study after having completed information disclosures assessments and gave consent.Primary inclusion criteria for the participants included: Exclusion Criteria:Parents could not participate in the study if one of them suffered from a serious mental illness due to its potential impact on outcomes. For the purpose of this paper, only datasets of mothers who gave premature birth were included, while results of fathers and parents of full-term babies were already published separately .Individuals were asked to complete anonymous paper datasets at their convenience within 3 days after birth of their child. 2(276) = 774.54 p < 0.001, and the Kaiser–Meyer–Olkin measure of sampling adequacy (0.61). We used the Kaiser’s criterion  to obtain the number of factors to be retained and ensured consideration for the amount of variance with the factor solution. In addition, the two criteria favored the four-factor structure . We found that the assignment of items to factors differed in comparison to the original version of the tool . This iMaternal stress was measured using the Parental Stress Scale , birth weight (grams), delivery route , and final APGAR score (APGAR points: A = appearance (skin color), P = pulse (heart rate), G = grimace (reflex irritability), A= activity (muscle tone), and R = respiration).age (years);marital status ;education level );work situation ; andnumber of children in the household including the newborn participating in this study.The following socio-demographic information was collected from mothers:Data analysis was performed by the SPSS program, version 26. Descriptive statistics (mean (SD); n (%)) were generated for all the variables included in this study. In the first step, we calculated the Pearson correlation coefficient in order to verify the relationship between PBQ and the maternal variables , and Spearman’s correlation coefficient for socio-demographic characteristics and the child’s characteristics variables.The second set of analyses included examining the predictors of maternal postpartum bonding; thus, we calculated the linear regression between postpartum bonding and those variables, which were statistically significant in the first phase of the correlation analysis.To test the mediating models, we followed Model 4 of the PROCESS macro for SPSS . We usedFinally, we undertook a moderator analysis following Model 1 of the PROCESS macro for SPSS . This anEligible participants who matched the selection criteria were recruited between April 2019–March 2021. Of the 100 women included in the project, 72 fully completed the PBQ. The mothers’ average age was M = 31.44 years old (SD = 4.81). All of the children were delivered before 37 weeks of gestation with an average gestational age of M = 33.54 . In terms of the sub-categories of preterm birth with regard to cut-off weeks of gestational age at delivery, the majority of newborns were late preterm , followed by moderate preterm , very preterm , and extremely preterm . Among the children, 55.6% were girls and 63.9% were delivered by caesarean section with the average weight in grams of M = 2201.58 (SD = 602). The average result on the APGAR scale was M = 8.42 (SD = 1.45), while only 23.6% of children received the maximum number of points on the Apgar scale.The average level of postpartum bonding is M = 7.87 points , indicating a very good emotional relationship between the mother and the newborn child. As can be seen from The analysis aimed to indicate the initial correlations between Maternal-Infant bonding and postnatal depressive symptoms, stress, and anxiety in the tested group. The obtained Pearson correlation results showed strong positive correlations between the overall result of maternal bonding and stress. The remaining correlations were not statistically significant .Further statistical tests revealed a lack of significant Spearman correlations between the child’s variables  and socio-demographical variables  with postpartum bonding .The obtained results show a positive, moderate correlation between Maternal-Infant bonding and both educational level and number of children. In addition, a positive but rather weak correlation appeared between Maternal-Infant bonding and maternal age. The remaining correlations were not statistically significant.The next stage of the research analysis focused on the relationship between the postpartum bonding and the research variable, limited to maternal stress and maternal age. Sociodemographic variables, child’s characteristics, and maternal depressive symptoms and anxiety were excluded from the regression analysis due to the lack of significant correlations between these variables and maternal postpartum bonding, as demonstrated in the first phase of the correlation analysis. Even the education level and number of children in the household reached statistical significancy in Spearman correlation; thus, we decided to exclude it from regression analysis due to too large diversity and considering the small sample size .p < 0.01, and explained 49% of the variability of the dependent variable. Conducted regression analysis in the studied group showed the significant role of the overall scores of stress experience (measured with the PSS). It can be concluded that the higher the stress score in the studied group, the more problematic postpartum bonding is between a mother and her child. The results obtained are presented in the table below  = 30.689, le below .Following the literature , we creaTo test the first model, we used 5000 bootstrap resamples to generate CIs for the indirect effect of maternal postpartum depression on maternal postpartum bonding via maternal stress  = 0.04; Bootstrap upper level 95% CI (ULCI) = 0.39). The tested model  proved tIn terms of the second model, we used 5000 bootstrap resamples to generate CIs for the indirect effect of maternal anxiety on maternal postpartum bonding via maternal stress  = 0.04; Bootstrap upper level 95% CI (ULCI) = 0.34). The tested model  proved tOverall, the mediating models revealed the significant affect of direct relationships between the analyzed variables in both cases. However, the relationship between postpartum depressive symptoms (the first model) and maternal anxiety (the second model) through stress on maternal postpartum bonding remained statistically insignificant.Finally, we undertook a moderator analysis to evaluate whether the relationship between maternal postpartum bonding and maternal stress depends on the value of those variables, which were statistically significant in the first phase of the analysis. Therefore, we considered socio-demographical variables as potential moderators . The resConsidering the importance of maternal postpartum bonding in regard to a child’s development and in the circumstance of premature birth, this study aimed to elucidate maternal postpartum bonding and its associations with maternal mental health, socio-demographical factors, and a child’s characteristics among mothers in the early postpartum period. The most relevant finding showed that the stress experienced by mothers was found to be a predictor of maternal postpartum bonding among the tested variables. Moreover, mothers of prematurely born children had a good level of Maternal-Infant bonding. The results’ analyses have shown positive correlations between the overall result of maternal postpartum bonding, stress, and socio-demographical variables . Surprisingly, the study results did not show significant relationships between maternal postpartum bonding, maternal mental health (anxiety and depressive symptoms), and a child’s characteristics . In contrast to our expectations, maternal stress did not mediate the relationship between depression and maternal postpartum bonding, nor anxiety and maternal postpartum bonding. Furthermore, that relationship of maternal postpartum bonding and maternal stress was not moderated by the value of socio-demographical variables.With respect to the first research question, the findings of the study indicated that mothers of prematurely born children had a good level of postpartum bonding with the infant (the average level of postpartum bonding was 7.87 points). Results from previous studies examining the impact of premature birth on parental bonding are inconsistent and often contradictory. Some studies showed that the process of bond development between a mother and her child can be disrupted by preterm birth . In addiInterestingly in examining the second research question, results showed that the study sample had a moderate severity of anxiety symptoms (the mean GAD-7 scores was 13.60) and a relatively low level of experienced stress based on the obtained scores (the mean PSS scores was 32.81). The majority of the examined mothers also did not experience depression symptoms (the mean EPDS scores was 8.83); only 13.4% of mothers had a score greater than 13, which may indicate occurrence of serious depressive symptoms directly after delivery. The finding related to anxiety coincides with previous studies showing that preterm delivery adversely impacts mothers’ psychological state by increasing their level of maternal anxiety . HoweverPreterm birth entails immanent difficulties and is acknowledged as a very stressful experience for parents . ResearcConsidering the transition to parenthood is a very stressful situation, we evaluated two mediating models to check if depression and anxiety (independently) mediate the relationship between maternal postpartum bonding via maternal stress. The motivation to create models stemmed from previous studies  in whichWith respect to the fourth research question, the obtained results revealed a lack of significant correlations between maternal postpartum bonding and a child’s characteristics such as gestational age, birth weight, and final APGAR score. In contrary to our obtained result, some research findings suggested that the severity of the health status of the infant  and the The fifth research question examined whether maternal postpartum bonding is associated with socio-demographical variables such as age, education level, and number of children in the household. Positive correlations were found between socio-demographical variables  and maternal postpartum bonding. These results are in line with other research. For instance, a systematic review conducted by Korja et al.  showed tIn addition, we tested whether the relationship between maternal postpartum bonding and maternal stress is moderated by educational level, maternal age, and the number of children. The results have shown that this relationship does not depend on socio-demographical variables. To the best of our knowledge, we can say that the moderating role of socio-demographic variables with Maternal-Infant bonding and stress is not explored. According to the systematic review conducted by , none ofAs preterm birth is a global problem, various authors provide important insight to the ongoing debate about the mother–infant interactions following preterm labor. This study showed that maternal stress is associated with maternal postpartum bonding in mothers after PBT. Clinically, this is most relevant result that emphasizes the need of providing psychological support and resources for mothers who experience high levels of stress shortly after PTB in order to reduce their stress level. First moments of the postpartum period are crucial for the development of early parental bonding with an infant , especiaInconsistent findings among previous studies emphasize the need for further investigations of Maternal-Infant bonding after PTB in the early postpartum period. Developing more extensive theoretical models with mediators and moderators in order to obtain a more detailed picture of the relationships between maternal bonding and the factors that may impact the process of postnatal bond development would be beneficial. It would be also beneficial to examine the development of Maternal-Infant bonding in a prospective study to assess the trajectory of bonding. There are still many unanswered questions about the maternal postpartum bonding score among mothers in terms of the sub-categories of PTB with regard to cut-offs of gestational age. Additionally, further examination of the relationship between maternal mental health and socio-demographic factors with postpartum bonding is needed as the early parental relationship with a prematurely born infant may be a complex phenomenon.The major strength of this study is the consideration of various variables  in relation to Maternal-Infant postpartum bonding. It provides a more comprehensive picture of factors that may or may not be related to the postpartum experience of bonding among mothers after PTB. A key strength of the present study was the dataset used. We believe that the population of mothers of pre-term babies included in the current study could be considered as representative of mothers after PTB at the national level. The mothers average age in the current study was 31.44 years of age, which is consisted with the age of mothers giving birth to children in Poland (the median age was 30). The majority of mothers in the current study were in a relationship (80.6% were married and 16.7% in partnership). This is also in line with legitimate and illegitimate births in Poland, indicating that the vast majority of births take place in legally contracted marriages. The majority of mothers in this study had a university degree , which corresponds with the data observed by Statistics Poland which shows that more than half of the women (52%) giving birth in Poland have higher education . In addiIn this investigation, there are several sources of limitations. First, the generalizability of the study findings is limited due to the small sample size and the fact that the study was conducted within one medical unit; thus, the obtained data should be interpreted cautiously. The establishment of a tie between a mother and child in the early postpartum period is a complex phenomenon . In bondThe findings in this study emphasize that the experience of stress and socio-demographical variables  may impact the process of developing a Maternal-Infant bond among mothers after the preterm birth. The current findings add to a growing body of literature on maternal postpartum bonding evaluated immediately after PTB and highlight the need for interventions targeting those mothers who experience high levels of stress. Mother–infant dyads should be supported after PTB as the postpartum period can be highly sensitive for the growth of the mother–infant bond. In addition, in this study, particular attention has been given to the level of maternal postpartum bonding that was not disrupted by the experience of the preterm birth. Many studies suggested that prematurity does not generate a higher risk for insecure attachment when the infant reaches 12 months . However


Missing values are a key issue in the statistical analysis of proteomic data. Defining the strategy to address missing values is a complex task in each study, potentially affecting the quality of statistical analyses.We have developed OptiMissP, a dashboard to visually and qualitatively evaluate missingness and guide decision making in the handling of missing values in proteomics studies that use data-independent acquisition mass spectrometry. It provides a set of visual tools to retrieve information about missingness through protein densities and topology-based approaches, and facilitates exploration of different imputation methods and missingness thresholds.OptiMissP provides support for researchers’ and clinicians’ qualitative assessment of missingness in proteomic datasets in order to define study-specific strategies for the handling of missing values. OptiMissP considers biases in protein distributions related to the choice of imputation method and helps analysts to balance the information loss caused by low missingness thresholds and the noise introduced by selecting high missingness thresholds. This is complemented by topological data analysis which provides additional insight to the structure of the data and their missingness. We use an example in Chronic Kidney Disease to illustrate the main functionalities of OptiMissP. Proteomics can provide a comprehensive protein profiling of clinical and biological research samples. Recently this has enabled the discovery of proteomic biomarkers for patient stratification and disease activity. Sequential window acquisition of all the theoretical mass spectra (SWATH-MS) has enabled these advances as this data-independent acquisition (DIA) mass spectrometry technique guarantees high reproducibility in peptide identification and identifies more peptides than data-dependent methods . SWATH-MWhile SWATH-MS theoretically collects data on all the peptides, the resulting datasets often contain missing values. The origin of missing values in mass spectrometry is related to different events , 7, withUsually a thresholding strategy is complemented with the replacement of missing values using imputation methods. The choice of the most adequate imputation technique requires proper assessment of the type of missingness in the data, in order to avoid bias in the distribution of proteins and in downstream statistical analysis . VariousMICE  with R version 3.6.1.OptiMissP is dashboard implemented via R Shiny [As shown in The Uploader serves to upload text files of non-imputed (or pre-imputed) proteomics data, at the protein level. The files may have the day in either long or wide format, i.e. instances (patients) organized into rows and features (proteins) arranged into columns or vice versa.The imputation component implements the optional imputation of the data in real-time by allowing for method selection between MICE, MissForest, Probabilistic PCA, Expectation-Maximization algorithm, or Lowest Value; alternatively, the user may choose to upload a dataset already imputed.Explorative histograms are aimed at assessing the global missingness in the dataset. They show the frequency of missing values from both a patient  and protein  perspective.The fourth component presents the distribution of the mean protein intensity in the imputed versus non-imputed datasets and allows for the head-to-head visual comparison of the protein’s intensities in imputed and non-imputed data in the whole studied cohort. A slider widget allows for the selection of a missingness threshold: for the complete dataset, it filters out those with fewer missing values than the selected threshold . As the missingness threshold is selected with the slider, density plots illustrate the two distributions (in imputed and non-imputed data) and their overlap. Distributions’ peaks  are highlighted with a vertical dashed line. The graphic outputs are complemented with quantitative details about the number of considered proteins, the percentage of missing values in both imputed and not imputed datasets, and statistical parameters for a quantitative comparison between the distribution of imputed and not imputed data. These indicators include information about distributions’ quartiles and peaks (and their distance), and the p-value of the two-sample Kolmogorov-Smirnov test used to compare the two distributions.In this section, the user can choose a specific protein of interest by its code or name (as identified in the dataset) and observe its degree of missingness and the discrepancy between its intensities’ distributions in imputed and non-imputed data. This section and results of this component are reported in cluster_optimal R function.The TDA Mapper component performs a two-dimensional topological analysis to show data-driven topologies built from imputed and non-imputed data. The user can decide on which TDA Mapper parameters and missingness threshold to use. Additional features enrich the resulting network with information about the missingness in each node (determined by the mean percentage) and any observed clusters in the topologies (and the options to optimize these). Identification of clusters within the TDA network is based on the The OptiMissP dashboard interface is illustrated in The user can explore missingness thresholds with the comparative density plots of imputed and non-imputed data . This alFinally, the last tab focuses on the application of TDA Mapper . Here thTo assess the utility and usability of our tools, the Salford CKD SWATH-MS proteomic dataset’s missingness has been studied with OptiMissP dashboard. Visualization and assessment of the data shows that the 56% of the data are missing  and thatThe density plots in As described above, it is unknown if missingness in SWATH-MS proteomic data is characterized by MNAR, MAR or whether it is a combination of both. OptiMissP allows for the handling of imputation and feature elimination with specific missingness thresholds in accordance with a qualitative analysis based on proteins value distributions.Without this set of tools, we would have likely selected an arbitrary imputation method and missingness threshold: for example, a Lowest Value imputation and a 60%-80% threshold, as is common practice in many studies. From We tested the OptiMissP dashboard functionalities in two additional publicly-available datasets with differing sizes and species , 23. TheWhile there are numerous software tools to manage raw data from mass spectrometry (at the peptide level) , there iData-independent acquisition proteomics has increased in use over the last decade with data imputation seeing widespread use in almost all processing software. The assumption in much of this software for data-independent acquisition is that missing values are a result of low abundance proteins and as such, methods such as imputing the lowest observed value or fixed low numbers are employed. MSstats, for example, has been utilised for both imputation and protein summarisation in both label free DDA approaches and data-independent acquisition, and by default uses an accelerated failure model after median normalisation .We present here a dashboard for the visualization and exploration of missing values in high throughput pre-processed proteomics data. The dashboard includes a set of tools aimed at guiding researchers in the handling of missingness within their studies, allowing for the identification of an initial strategy based on a qualitative evaluation of missingness by comparing different imputation approaches.Using data from the Salford Kidney Study CKD proteomic dataset, we demonstrate the utility of the OptiMissP dashboard. In this example, exploration of missingness in the data suggests that a MAR imputation method is preferable, as is applying a high missingness threshold (i.e. 90% threshold). Given that the enrichment with the patients’ percentage of missing values indicate different patient distributions within the different TDA networks , and theThe OptiMissP dashboard is aimed at supporting a visual and intuitive assessment of missingness in a user-friendly manner; it is explainable and easily interpretable by users, as opposed to providing optimized solutions achieved by black-box algorithmic calculations.As recently discussed , differeWe acknowledge that root-mean-square error (RMSE) analysis would be the most appropriate approach to compare how imputation approaches handle missingness. However, since it is likely that complete observations  are not always available, as is the case in many SWATH proteomics datasets, that strategy was not feasible. Instead, we relied on the distance between peaks of the distributions, and use Kolmogorov-Smirnov test to compare imputed and non-imputed data sets. Future developments should include the RMSE computation. Additional developments of OptiMissP will be devoted to evaluating the usability and potential uptake of the tool by naive end-users. We will further enhance the tool with functionalities aimed at defining thresholds and imputation methods on a quantitative basis for multivariate prediction model validation and deployment ; as wellOptiMissP can aid research in addressing the issue of missingness in mass-spectrometry proteomics studies, supporting statistical analyses at the basis of proteomics biomarker discovery. We have implemented a data-driven visual process to explore missingness aimed at finding a balance between the removal of a great amount of informative data (i.e. choosing high thresholds of missingness) and the introduction of biases in protein distributions (i.e. using imputation methods that do not reflect the nature of the missingness). The dashboard fits into this context by enhancing clinician and researcher abilities to make better, informed decisions with respect to handling missing values, and retrieving information from missingness itself.S1 File(DOCX)Click here for additional data file.


Self-healing of a crack is a relatively novel technique allowing for the partial recovery of the initial mechanical characteristics of a structural element after some period of exploitation. By a widely accepted convention, self-healing is either autogenous or autonomous. The former is a mechanism inherent for cementitious composites (in particular—concrete), while the latter is an engineered process. Both autogenous and engineered healing have recently been the object of numerous studies. Despite the large amount of research work being carried out, the potential of this technique has not yet been fully realized. The article focuses on the modeling and the finite element simulation of the recovery of the initial material properties resulting from the sealing of cracks. The employed numerical procedure uses a constitutive relation for concrete based on the continuum damage mechanics. It captures both the strain-softening and the inverse process—the crack healing. Finite element simulations of benchmark cases illustrate the effect of self-healing. The numerically obtained constitutive relations for specimens with and without a healing agent are compared. The self-healing of cracks implies the material properties’ recovery resulting from the crack sealing ,2. GenerUsing environmentally friendly bacteria such as Bacillus pasteurii can replace the commonly used repair materials for concrete , which are environmentally unfriendly . Moreove2).Some authors ,8 attribThe partial substitution of cement with fly ash, as well as the addition of crystalline admixture, yields the recovery of both compressive strength and electrical resistivity of concrete up to 94% . AccordiPolymers , acrylamide, acrylate, epoxy, poly styrene-divinylbenzene, styrene-butadiene rubber, etc.) improve the rate of the regain in the mechanical properties and contribute to the healing of surface cracks .Reportedly, fibers (either steel or synthetic) in fiber-reinforced concrete control the crack opening what results in ease of application of the self-healing products in terms of adhesion to the crack surface and crack filling. Thus, according to , in engiUltra-high-performance concrete (UHPC) and ultra-high-performance fiber-reinforced concrete (UHPFRC) have the potential to exhibit self-healing capacity because of the high binder content and the low water/binder ratio ,20,21. AThe modeling of the self-healing of concrete is in close relation with the simulation of the concrete failure behavior. The fracture of concrete has been investigated in numerous research works ,42,43,44Among other approaches suitable to model the self-healing phenomena, Yang et al.  discuss The deterministic approach to the analysis is often questionable, considering the high scattering in material properties within structural elements and loading. The stochastic perturbation-based finite element method theoretically addresses this issue .Recent studies extend the finite element method by proposing a new finite element formulation with embedded strong discontinuity  or by coIn Ref. , by hypoIn , by assuCombining the finite element method (FEM) and the discrete element method (DEM) has drawn considerable research attention ,62,63,64The combined FEM–DEM formulation implies a multi-scale approach. The frictional contact properties of the interacting discrete particles (for the DEM) are defined at the micro-scale, while the material properties for the FEM generally reflect experimental data obtained at the macroscopic scale. The multi-scale approach involves an identification procedure  that genOñate et al.  use the Both aforementioned approaches imply complicated numerical procedures accounting for crack initiation and propagation in the continuum. On the other hand, the complication affects only a part of the initial computational domain. The article focuses on the numerical simulation of the opening and reclosure of cracks, to model the material properties degradation, due to the former mechanism and the material properties recovery attributed to the latter.A simplified solution scheme using the finite element method only is applied. Using different methods for different phenomena might be intuitive and consistent. On the other hand, continuum mechanics  describes the microscope manifestation of mechanisms that take place at the microscopic scales. The employed damage model slightly differs from the standard damage model incorporated in the advanced numerical simulations referenced above. The numerical algorithm uses an original procedure that integrates the damage variable into the material constitutive relation. Generally, the concrete fracture is described either by using fracture mechanics or in the context of damage mechanics. Damage mechanics is the preferred option in this study since it allows for modeling the damage accumulation and crack propagation starting with homogeneous isotropic material. Unlike the fracture mechanics approach, there is no need to pre-establish defects in the studied specimen to initiate macroscopic cracking. The present article develops and summarizes some ideas discussed in previously published contributions ,66.The underlying hypotheses of the reported study presume that mechanical loading triggers the crack opening while the regain in the mechanical properties results from engineered self-healing. Continuum damage mechanics allows for the modeling of the degradation of the initial mechanical properties via the introduction of a damage variable into the material stress–strain relationship. The damage variable is regarded as an operator acting on the elasticity tensor. Thus, damage variable increase models the damage accumulation in the material, and a critical value of the damage variable corresponds to macroscopic crack initiation in the specified location. Vice versa, the sealing of cracks results in a decrease in the damage variable and a partial regain in the initial mechanical properties. Finite element simulations of some benchmark examples illustrate the self-healing mechanism. Modeled specimens are damaged to introduce multiple cracking patterns . Then, at a specific moment of the loading history, the activation of the autonomous self-healing leads to a sealing of the formed macroscopic cracks. This mechanism results in a partial regain of the initial material properties. The focus of the article is on the finite element analysis of concrete specimens containing a self-healing agent. Within the assumed approach, the material response of concrete is modeled via a coupling between elasticity and damage ,67.(1)σIn Equation (1), The damage variable acts directly on Young’s modulus. Theoretically, it evaluates the mechanical damage induced by the applied load.As shown in Equation (2), the damage variable depends on a set of material constants n tensor .(3)εeqvi, one set of two constants for tension, and another for compression control the shape of the numerically obtained stress–strain relationship. In Equation (3),The constant Damage accumulates provided the variable defined in Equation (3) becomes larger than another model parameter, the damage threshold:Reaching the critical value of the damage variable at a specific location in the continuum The activation of the self-healing process leads to the sealing of the newly formed cracks and regaining the initial rigidity in some regions. Therefore, self-healing is modeled by setting the damage variable equal to zero and the Young modulus—equal to its initial value. At the same time, some level of damage remains in regions where the damage variable has not yet reached its critical value. Standard compression and tension by flexure tests, as well as a torsion test on concrete specimens, are simulated. Simulations include a preloading phase without reaching the failure load of the specimen. The preloading phase induces some damaged state in the specimen. Also, in some regions, the critical value of the damage variable is reached , and the self-healing process is launched . The responses of the specimens are obtained by finite element analysis in terms of stress–strain relationships.The evaluation of the self-healing effectiveness employs an assessment of the recovery of the relevant mechanical properties . ConcretThe general-purpose finite element code ANSYS is employed for the numerical simulations. A compression test on a cylindrical concrete specimen, a tension by flexure test on a prismatic concrete specimen, and a torsion test on a cylindrical concrete specimen are simulated. Standard geometries are used for the simulations of the compression and the tension-by-flexure tests.The compressive strength of the concrete is measured on cylinders 150 mm in diameter and 300 mm in height, in accordance with ISO 1920-3 . Figure Tension by flexure test commonly performed on a prismatic concrete specimen is simulated. The modeled specimen is 400 mm in length, 300 mm in span, with a rectangular cross-section of 100 mm × 100 mm. The distance between the specimen end and the point load location is 100 mm . For the considered experimental setup, unstable crack propagation being a fast process, additional time-stepping, with the definition of a smaller time interval, might be required to capture it.The finite element analysis simulates a displacement-controlled experimental setup with a constant time step for the entire load history. The solid geometry is meshed with 1568 finite elements SOLID185 . To modeThe finite element simulation reported in this section reproduces the response of a cylindrical concrete specimen subjected to torsion without the ambition to reproduce accurately any experimental setup. Results obtained by finite element simulation have illustrated the effect of the self-healing of cracks. The strength recovery is 109.2%, 93%, and 96.75% for the specimens loaded in compression, flexure, and torsion, respectively. By assumption, the strength recovery is the ratio of the peak values of the stress or moment in the healed and the pristine specimens.Further implementation of the employed numerical procedure (as a design tool) requires extensive experimental work. The identification of the model parameters, specifically of the critical value of the damage variable, is inherently empirical. Presumably, the aforementioned critical value of the damage variable is directly related to the crack opening and, thereby, the healing process initiation.The damage-based constitutive relation slightly differs from that implemented in recent research. For example, in , the tenVery detailed modeling at the mesoscopic scale has been proposed by . To modeAlthough the self-healing of cracks emerges as a technique capable of enhancing the durability and sustainability of structures, it still possesses some limitations. The major one is that self-healing results in only a partial regaining of the performances of the undamaged material. According to the vast majority of literature sources, the healing rate remains less than 100%. For comparison, alternative techniques for refurbishment, such as strengthened with externally bonded composite materials, provide a net increase in the load-carrying capacity and stiffness. Also, engineered self-healing implies taking actions during construction . In this context, post-strengthening appears to be more flexible for existing structures, especially not equipped for self-healing. On the other hand, when programmed, the engineered self-healing is expected to run as an autonomous process presuming less maintenance and repairs (during the life cycle of a structure).Despite some shortcomings, the self-healing of cracks remains a field of active research because of the attractive perspectives. Besides autonomous healing, self-healing includes mechanisms inherent for concrete. Accurate quantification of the natural phenomena in the concrete leading to its longevity will contribute to a more efficient design of sustainable structures.Numerical simulations of the self-healing process in plain concrete specimens have been presented and discussed. Results obtained by finite element simulations of a compression test, tension by flexure test, and torsion test for healed and pristine specimens of the same geometry have been compared to predict the recovery in strength.Both material degradation and healing are modeled implicitly in the framework of the continuum damage mechanics. The numerical algorithm integrates into the finite element analysis an original procedure designed to simulate the strain-softening concrete response and extended to account for the effects of healing. The computational procedure uses only the finite element method. It does not include any additional computational scheme to decouple effects due to different mechanisms . The framework of the continuum damage mechanics is preferred to that of fracture mechanics as it enables modeling of crack propagation and initiation in an initially homogeneous and isotropic material . Numerical results reproduce the response of the pristine specimens well, whereas the estimated recovery in strength for some tests is unexpectedly high, accounting for the empirical data provided by previous  research works. In this context, a forthcoming experimental campaign can provide additional empirical background for the model validation and the identification of the material constants.The presented study considers only the healing of specimens subjected to a quasi-static loading. Simulations of the behavior of structural elements under various loading conditions are forthcoming.


This study presents the case of a brain-injured patient whose pathological awakening after coma and absence of interaction led to a diagnosis of lack of consciousness when standard clinical scales were administered. However, we were able to demonstrate conscious perception in this patient from initial clinical assessments using the Motor Behaviour Tool in the acute stage, complemented by a systematic search for potential obstacles blocking his execution of motor responses . This refinement of the diagnosis enabled prediction of a favourable outcome despite the severity of the lesions, with the patient’s evolution confirming our prediction. Faced with an unresponsive patient, every specialist should go beyond the absence of response with the standard scores, consider the possibility of a hidden consciousness and look for rigorous ways of proving it. Over the last 15 years, specialized neurobehavioural rating scales have been developed to provide a reliable means of assessing consciousness. The Coma Recovery Scale-Revised (CRS-R) is currently used as the gold standard in the diagnosis of disorders of consciousness (DOC) in the subacute and chronic settings . Indeed,. On a pathophysiological level CMD reflects strategic lesions impairing the motor output channels. Patients with CMD can be diagnosed clinically because the likelihood of a complete disruption of all motor output channels is low. In fact, if many motor output channels are disrupted, the patient is probably suffering from widespread lesions, causing not only true impairments of awareness (no positive MBTr signs) but tell-tale signs of DOC (negative MBTr signs), such as stereotyped posturing . Therefore, subtle signs of intentionality after adequate stimulation can be detected by means of the MBTr in most clinical CMD patients. Furthermore, the sensitivity of this tool is unaffected by the presence of confounding clinical factors  that interfere with sensory and/or motor afference or intrinsic brain activity [It has been shown by our group that the Motor Behaviour Tool-revised (MBTr) can reveal residual cognition in almost two-thirds of acute patients diagnosed as behaviourally unresponsive by the CRS-R . The MBTactivity .Here we describe the case of a brain-injured patient presenting with several pitfalls and consequently diagnosed as unresponsive based on the CRS-R only, while clear signs of conscious perception were identified by means of the MBTr.A 53-year-old patient with no previous medical or psychiatric history was admitted to our emergency department after a severe brain injury  following a car accident. The patient needed endotracheal intubation and sedation, and his initial clinical examination showed reactive symmetrical pupils. An emergency computed tomography (CT) total body scan revealed numerous lesions: inferior vena cava laceration, abdominal bleeding and left inferior limb fractures. A cerebral CT-scan revealed a right parietal sub-arachnoid haemorrhage and left maxillary bone fracture. There were no signs of brain swelling and basal cisterns were free. As an emergency surgery was required to treat the inferior limb fracture and abdominal bleeding, an intracranial pressure monitoring was implanted to drive the neuro-reanimation. An intensive neuro-reanimation was required over the following days to attempt to get values of intracranial pressure below 15 mmHg. After 48 h, despite a maximal neuro-reanimation treatment with curare and hypertonic solution, intracranial pressure was refractory to medical treatment and a surgical treatment through right decompressive craniectomy was decided, which resulted in the normalization of intracranial pressure. Strict neuro-reanimation procedures continued for 3 days, and sedation was withdrawn 10 days post injury. A tracheotomy was performed 10 days later.Twenty-four hours post-sedation withdrawal, the patient presented a pathological awakening with absent external responsiveness to stimulation. Hence, he was clinically assessed by two experienced physicians by means of the CRS-R and the MBTr , alongside diffuse hypometabolism of the cerebellum.Electroneuromyography (ENMG) demonstrated a reduction in amplitude of the motor responses by stimulation of the peroneal and musculocutaneous nerves. The moderate abnormalities observed were compatible with a mild critical illness polyneuropathy yet did not account entirely for the tetraplegia observed in the patient.Over the 6-week period in the acute neuro-rehabilitation unit, the patient underwent an individualized intensive multidisciplinary rehabilitation program.The neurological examination and outcome at discharge are detailed in This case study presents the history of a patient whose pathological awakening after coma and lack of interaction led to a diagnosis of absence of consciousness when only the standard scales were administered. Nonetheless, we were able to demonstrate conscious perception in this patient from early clinical assessments in the acute stage using our specialized motor behaviour observation tool, the MBTr, complemented by a systematic search for pitfalls that could hinder the production of motor responses. The refinement of the diagnosis helped to predict a favourable outcome despite the severity of the lesions, and the patient’s evolution confirmed our prediction.Our case illustrates several important points in the pursuit of an accurate and correct diagnosis of consciousness disorders in the acute phase. Firstly, the presence of conscious perception is correlated with a better prognosis, which contributes directly to decisions made in the intensive care unit about whether or not to continue care and the information given to the families .Secondly, the identification of the pitfalls hindering the adequacy of motor responses that may then totally or partially mask a conscious perception in a patient appearing unconscious is essential. Indeed, in a retrospective cohort study we previously demonstrated a high prevalence of patients presenting confounding factors leading to misdiagnosis of their state of consciousness .In the case described here, we found three major coexisting pitfalls, which deserve further consideration. The prominent deafferentation of the subcortical structures  are associated with severe damage to the regulation of arousal and functional integration of the forebrain, explaining the significant fluctuations in the patient’s alertness . In addiThe frontal syndrome coming from disconnections in the frontal cortico-subcortical motor pathways determines a condition close to akinetic mutism accounting for the absence of behavioural reactions despite sustained stimulation . MoreoveThese interpretations may be also based on the mesocircuit model according to which CMD patients present a functional impairment of the forebrain systems associated with motor preparation and action , differeFinally, previous studies showed that 40–80% of critically ill people presented with acute polyneuromyopathy , motivatThe present case study has several limitations. First, we categorized the patient as presenting with clinical CMD only on a clinical rating from MBTr evaluation. We did not perform an active mental-imagery task to confirm the clinical diagnosis . FurtheThis case illustrates the importance of establishing a detailed and structured diagnostic procedure in early clinical detection of consciousness using a simple clinical observation tool combined with a comprehensive neurological examination of the primary neurological pathways complemented by a systematic search for pitfalls hindering responses. Faced with an unresponsive patient, and despite the necessary rapidity of clinical examinations in the acute stage, each specialist should imperatively weigh up their diagnosis, consider options other than the standard scales and base their evaluation on all the elements that are possible to acquire. The absence of proof is not proof of absence, and a wrong diagnosis may lead to ethical and prognostic implications of great importance.


Since increasing life expectancy leads to a longer period of retirement, several studies have been investigating the possible impact of retirement on cognitive health. Several epidemiological studies with cross-sectional designs have reported a negative association between retirement and cognitive capacities. However, very few studies with longitudinal designs have confirmed the negative effect of retirement on cognitive functioning. The present study was conducted to investigate the impact of retirement on cognitive capacities among older Canadians. We used data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA) to compare performance retirees and workers (N = 1442), 45 to 85 years of age at baseline. Memory and executive functioning were assessed using standardized assessment tools at baseline and at three-year follow up. Retirees and workers were matched for age, gender and education using the nearest neighbor propensity score method with a caliper of 0.02. Mixed ANOVA and post hoc analyses were conducted separately for the English- and French-speaking samples. Results for the English-speaking sample showed a significant decline on both the Stroop and the Mental Alternation Task for retirees compared to workers from baseline to follow-up. These results support previous cross-sectional studies that have demonstrated a negative effect of retirement on executive functioning. The absence of significant results in the French-speaking sample will be discussed in terms of sample size and professional occupation.