Blending a certain proportion of basalt fiber into concrete improves the toughness of concrete, which prevents cracking and avoids the brittle behaviors. In this paper, the compressive, tensile, and flexural tests of concrete with different basalt fiber contents were carried out. Then the test phenomena, failure modes, and mechanical properties were compared and analyzed to derive the relationship between the basalt fiber contents and mechanical properties. The toughness and crack resistance performance of basalt fiber reinforced concrete were evaluated by the fracture energy, advanced toughness parameters, and characteristic length proposed by Hillerborg. The correlation coefficient of basalt fiber was introduced to establish the calculation formula for mechanical properties of basalt fiber reinforced concrete. The results indicated that basalt fiber significantly improved the toughness and crack resistance performance of concrete. The enhancing effect of the basalt fiber on the compressive strength of concrete is lower than that of tensile strength and flexural strength. Moreover, the improvement effect was the highest with the basalt fiber content was 0.3% and 0.4%. Concrete has the advantage of high compressive strength, superior corrosion resistance, and relatively lower cost, therefore, it is still the most widely used building material in the world. However, as one type of artificial brittle materials, concrete is relatively insufficient in terms of tensile strength, bending resistance, impact resistance, and toughness. As the service time increases, the defects of concrete become increasingly prominent, which leads to many problems in engineering applications.At present, it is internationally recognized that fibers are able to be added to concrete to overcome the defects of concrete. In the past two decades, blending fibers into concrete has been widely applied in some projects ,3,4,5,6,Commonly the composite material theory and the fiber spacing theory are adopted to explain the reinforcement mechanism of fiber reinforced concrete. The former is built on the mixing rule of composite materials and the latter is the perfect bond theory between fiber and matrix. They explain the reinforcement effect of fiber on concrete from different perspectives. The theory of composite materials  regards Basalt fiber has significantly different characteristics from other high-tech fibers ,20,21,22Moreover, as a multifunctional fiber, basalt fiber possesses comprehensive and excellent quality: acidic and alkaline resistance ,24,25,26There are relatively many researches on the volume content of basalt fiber. In this paper, the representative research results on the optimum content of basalt fiber reinforced concrete in recent ten years are shown in the The research results show that the reinforced effect of basalt fiber in compressive strength is not obvious, but that in terms of tensile resistance and flexural properties resistance are better. As can be seen from the above table, most of the research on tensile properties resistance adopts split tensile test. For direct tensile test, due to the limited conditions required by the test, the related research is relatively few. At the same time, the dispersion of the optimum volume content is relatively large, the main reason is that the evaluation method of basalt fiber reinforced concrete is lack of relevant unified method, the experiment of related properties is relatively single, there are also differences in the pouring method of basalt fiber reinforced concrete and the physical parameters of the selected fiber.In this paper, the basalt fiber content was adopted as a single variable to study the influence of basalt fiber content on the mechanical properties of concrete. Combined with test results, the toughness and crack resistance performance of basalt fiber reinforced concrete were evaluated by the fracture energy, advanced toughness parameters, and characteristic length proposed by Hillerborg and the best volume content was obtained. Meanwhile the correlation coefficient of basalt fiber was introduced to establish the calculation formula for mechanical properties of basalt fiber reinforced concrete.According to GB/T 50081-2002 “Standard for test method of mechanical properties on ordinary concrete” and CECS 13-2009 “Test method for steel fiber reinforced concrete”. Three kinds of specimens were prepared for compression test  according to GB/T 50081-2002 ”Standard for test method of mechanical properties on ordinary concrete” and CECS 13-2009 “Test method for steel fiber reinforced concrete”. In order to prevent producing stress concentration near the embedded bar, the embedded part was tied with claw type vacuum wires above the front, as shown in JGJ/T 221-2010 ”Technical specification for application of fiber reinforced concrete”, we selected P∙O 42.5 Portland Cement, the sand from the river in Mianyang, China, whose modulus of fineness was about 2.5 (sand ratio 30%), local ordinary gravel stones (16 to 20 mm), and the local tap water. The water-cement ratio of cast-in-place concrete was 0.42, and the collapse degree is 30–50 mm. according to the SL677-2014 “Specification for Hydraulic Concrete Construction”. The concrete’s mixture ratio was shown in According to GB/T 50080-2016 “Standards for Test Method of Performance on Ordinary Fresh Concrete” and CECS 13-2009 “Standard Test Method for Steel Fiber concrete”. A forced mixer was used to mix BFRC . The secondary mixing method was adopted to avoid fiber agglomeration. First, fine aggregate and basalt fiber were mixed dryly for 30 s until they were evenly mixed, and then coarse aggregate, cement, and water were put in. All materials were stirred for 280 s after putting in. Vibro-compaction moulding technology was used to pour concrete into the moulds for moulding. After 24 h, the specimens were removed into the Standard Curing Room for curing.The preparation, pouring, and curing of concrete specimens were in accordance with GB/T 50081-2002 “Standards for Test Method of Mechanical Properties on Ordinary Concrete” and CECS 13-2009 “Standard Test Methods for Steel Fiber Concrete”, loading rates of compressive, tensile, and bending tests were 11.25 kN/s, 0.04 mm/min, and 0.01 mm/min, respectively.According to In the tensile test, the main difficulty is the axis alignment of specimen clamping. Therefore, the pre-embedded bars at the end of the test piece were connected to the load testing machine through the Spherical Plain Bearing, as shown in With the increase of load, the plain concrete specimen (B0) was crushed with a loud noise. Surrounding concrete was crushed and spalled after maximum load due to the cyclo-hoop effect, and concrete block was pyramidal, as shown in For the BFRC , the crack width increased gradually after cracking with debris fell. The cross sectional area showed an external drum shape. However, the specimen cracked but was not broken. Their destruction was not as sudden and quick as that of B0. The first sound of destruction was noisy and tearing and finally destruction was followed by a dull sound .For the plain concrete specimen (B0), the load increased steadily along with the increase of displacement in the early stage of the test. When the deformation was close to the ultimate displacement, the increase amplitude of the load value had no obvious change. When macroscopic cracks appeared in the middle of the specimen, the specimen broke into two sections, the cracking process was extremely fast, and the section was smooth and clear .For the BFRC , the load increased linearly with the increase of displacement at the initial stage of loading. When the deformation approached the ultimate displacement, the growth rate of the load slowed down. When macroscopic cracks were observed in the middle of the specimen, the specimen was broken into two sections with clear but uneven fracture. Similar to the case of plain concrete, the fracture sound of BFRC was smaller and there were a lot of tensional fibers in the fracture surface. Because the elastic modulus of basalt fiber was too low to bear the load effectively, the tensile load was close to zero. The specimen continued to be stretched, the fibers at the fracture were observed to be pulled off after the fracture, which indicated that basalt fiber had a fine bond performance with concrete .In the process of bending test, the failure of plain concrete (B0) was very sudden and rapid. With the increase of load, the specimen was quickly break into two parts after cracks appear. However, for BFRC there was a certain buffer time from the appearance of cracks to the fracture. Although time was very short, it proved that the toughness of concrete was indeed improved. In terms of crack width, it can be obviously observed that the crack width of BFRC was larger than that of plain concrete .Through compressing test and bending test, the mechanical properties parameters of BFRC can be obtained as shown in Due to the limited data in this paper, the relationship between compressive strength ratio, flexural strength ratio and fiber characteristic value  that there was a poor agreement with fitted curve and experiment data. The results show that the compressive strength of concrete has not been significantly improved by the incorporation of basalt fiber.f0f is bending strength of the plain concrete; 2γ is the influence coefficient of bending strength related to fiber dispersion and pouring process, as shown in Relationship between bending strength and volume content of basalt fiber:From x-coordinate. Combined with the methods of ASTM-C1080 and JSCE-SF4, an advanced toughness evaluation method was proposed in this paper. The peak deflection of 0.5, 1.0, and 1.5 times was selected as the reference deflection, i.e., 0.5cδ, cδ, 1.5cδ. Accordingly, the toughness was evaluated by the area of 1A, 2A, and 3A, as shown in I0 and I1, see Equations (3) and (4). In addition, the specimen had been damaged and had basically lost its bearing capacity under the larger axial displacement. Therefore, there was no significance to make the further analysis and discussion here.The ductility of concrete is the ability to maintain deformation after cracking, that is, the area enclosed by the load-displacement curve and I0 reached maximum; the volume content was 0.3%, the toughness index I1 was the largest.The results  showed tcδ was the displacement corresponding to the peak load; 1A was the area which was formed by curve OA and X axis, that was area of polygon OAE; 2A was the area which was formed by curve AB and X axis, that was the area of polygon ABEF; 3A was the area for curve BC and X axis which was the area of polygon BCFG.In The relationship between volume fraction and toughness index was shown in 00I and 10I are toughness index of the plain concrete. 0β and 1β is the influence coefficient of toughness index related to fiber dispersion and pouring process, as shown in 0β = 0.112%, 1β = 1.455.The relationship between toughness index and volume content was expressed as:According to the Equation (5), Equation (6) and fG). This paper is based on the calculation of the area of the peak load deflection under 1.2δf curve, as shown in Bending toughness of BFRC can be evaluated by the fracture energy . Based on the bend-press ratio of plain concrete, the enhancement coefficient was introduced and finally the equation for bend-press ratio of BFRC was obtained by Equation (9).The relationship of enhancement coefficient and volume content was expressed by Test results showed that basalt fiber can improve the crack resistance of concrete. With the increase in volume content from 0.1% to 0.4%, the bend-press ratio of BFRC was increased, obviously.Through the tensile test of BFRC, the full tensile stress-strain curve of BFRC was showed in As seen in t0f is tensile strength of the plain concrete.The relationship between fiber characteristic value and tensile strength ratio were drawn based on the test results : ω is the crack expansion width, (mm); eδ and 0δ are the elastic deformation and residual deformation, (mm); pσ is the peak stress, (MPa); 𝑙 is the gauge length of the specimen, (mm); pδ is the peak stress corresponding deformation (mm).In the tensile process of BFRC, the total deformation , the crack expansion width can be expressed:Then, the relative stress-crack width curve  and the The empirical equation derived by scholars  was as fAndrσ is the relative tensile strain; rω is the relative crack width; a = 0.0418, b = 1.3082, n = 0.4932, α, β, n were all related to the type, aspect ratio, density, other physical and mechanical parameters of basalt fiber.With the method of fitting regression, the new expression was obtained:0ω is maximum crack width of plain concrete; ψ is the influence coefficient of maximum crack width, ψ = 0.1173%.According to the test results in The fracture energy of concrete is an important parameter to characterize the energy consumption in the process of concrete fracture and crack propagation. The greater the fracture energy was, the more the energy consumption in the process of fracture was. The fracture energy of BFRC was more than that of plain concrete. The main reason was that the basalt fiber needed to consume energy when it was broken. This also indicated that the fracture resistance of basalt fiber was effective. Different from the above calculation method of fracture energy, another method  was adopFracture energy specifically referred to the energy consumption of cracks per unit area, which was shown on the curve as the ratio of the area under the load-crack width curve to the cross-sectional area of the specimen, that was, the area under the stress-crack width curve:The test results of fracture energy were shown in It can be seen that the fracture energy of concrete increased with the increase of volume content . The fitThere are many methods for characterizing the fracture properties of concrete . This paThe specific dates of the characteristic length of each specimen were shown in As above, the related work was carried out on the mechanical properties such as strength, toughness, crack resistance, and energy dissipation under various stress states. The effect laws of volume content of basalt fiber on each mechanical property parameter were found simultaneously. Interfacial bonding reliability between concrete and basalt fiber played a tremendously essential role in potentiation. With the failure mode of fracture surface, the bonding property was authentic between basalt fiber and concrete. It can guarantee that the force applied to matrix was transferred to fiber via the surface of basalt fiber and concrete. Micro-crack of concrete developed toward macro-crack, then basalt fiber which across crack became the main undertaker of external force when the external load increased to a certain extent. Furthermore, due to higher performance for extension strength and toughness of basalt fiber more than concrete, the stress concentration at the crack tip was mitigated and the extension resistance of crack was increased. So the tension resistance and bending resistance were reinforced. Additionally, a certain amount of energy was consumed during the process of resisting the extension of crack, thereby the fragility crack was relieved at some extent.(1) Micro-fracture of ConcreteIn the early after concrete pouring, there is a possibility of concrete bleeding that many capillary bleeding channels will be formed inside naturally, some moisture will transfer to surface and then be evaporated, more, when the transfer speed is slower than evaporation, this moisture will develop from surface to the inside and curvature is going to be increased in this condition. According to capillary principle, we know that concave surface is going to be shrank under the force of inside tension, capillary wall is under tensile condition resulting from inside negative pressure, additionally, if this compression keeps increasing, then there will be crack in the concrete surface, later, many cracks will form fracture which can be the micro reason for forming micro-fracture.Propagation of crack does matter intensity, deformation, and destructive property. Cracks which are formed before undertaking load can be divided into randomly distributed micro-crack and directional macro-crack. In the cracking, concrete is mainly under control by micro-cracks, on the one side, micro-crack will develop into macro-cracks, on the other side, it will have dual effects on main cracks on shielding and degradation.(2) Crack Resistance Effect in the Process of Shrinkage of ConcreteThere will form a three-dimensional chaotic network system which equals secondary reinforcement effect that decreases the separation between aggregate in the surface and bleeding restraining generation and development of segregation crack and stopping from developing fracture after certain basalt fiber were added into concrete. It’s easily to form shrinkage crack in the early pouring period resulting from hydration reaction and evaporation between concrete and water and lower strength of extension. Compared with plastic slurry, basalt fiber is a little bit higher in elasticity modulus, the adsorption bonding force will disperse some of the shrinkage energy to the fiber mono-filament, increasing strength of extension so that it can efficiently restrain the production and development of micro-cracks, especially for interconnected fracture, at some extent, it increases the degree of density of concrete. In addition, the fiber in the surface material increases the difficulty of water transfer, thus reducing the tension formed by capillary water loss and contraction, as well as the evaporation of water, which can improve the water retention of concrete.(3) Crack Resistance Effect in the Process of HardeningThere are three types of shrinkage for concrete in the process of hardening: drying shrinkage, temperature shrinkage, and carbonization shrinkage. Drying shrinkage which refers to the shrinkage due to the capillary stress for evaporation of inside moisture. Temperature shrinkage can be a “thermal contraction” which forms in the process of using or the ambient temperature drops. Carbonization shrinkage refers that after hydration, due to chemical reason, the concrete will form calcium hydroxide, then the carbon dioxide will infiltrate through capillary channel and form calcium carbonate reacting with calcium hydroxide. And, the size for it is small, then can lead to shrinkage. The shrinkage above will form tensile stress and form fracture under constraint condition. The steel fiber in concrete can not only withstand the tensile stress reducing the generation of cracks, but also reduce the stress concentration at the tip of micro-cracks preventing the expansion of micro-cracks, preventing the appearance of connected cracks. When cracks are being developed, the fiber will cross crack like a bridge for interconnection between fiber and cracks and short distance, due to this transfer, which ease the stress concentration in the front of micro-crack leading to more continuous and uniform field of stress inside of concrete then restraining forward development of micro-cracks at some extent; Also, when the space of fibers is longer than micro-cracks, then fibers will form blocking effect and change its extension ways or micro-cracks will cross fibers so that they can be separated into finer crack space which does stops from producing and developing micro-cracks.(4) Toughness Strengthening Mechanism of Basalt Fiber ConcreteAccording to the observation to the failure state of basalt fiber, it can be obtained that basalt fiber is mainly by means of stopping the production and development of crack to slow down its steady expansion before failure, more, it has an effect of stopping from cracks and increasing toughness through micro-crack parts or fracture transition parts in the crack tip.Seen With the increase of load, micro-cracks inside of basal part developed steadily into macro-cracks, then the load deflection curve was going to be nonlinear variation. In this stage, due to boding force, basalt fiber transferred stress across the fracture, and the basalt fiber concrete still could load more. More the load, more the development of cracks, then basalt fiber reinforced concrete was in the elastic-plastic stage. After the process for pulling out fiber little by little until it failure, the load capacity for it still was improved and increased more with the increase of volume content.After basalt fiber concrete reached its critical value for load, then the cracks were developed. Resulting from the critical value of bonding force between basalt fiber and basal part, the basalt fiber was pulled out until broken leaded to failure of load capacity. The basalt fiber concrete at both ends of the crack almost turned into a rigid body and the mid-span deflection increased rapidly. In this process, as more and more volume content of basalt fibers was falling off, pulling out or broken, they needed to absorb a lot of energy, so the load deflection curve dropped slowly, showing good toughness, and had the characteristics of cracking and continuous. It can also be seen from the curve that the larger the fiber volume content was, the fuller the curve descending section was, and the higher the toughness of fiber concrete was.While under the compressed condition, fibers along the direction of force suffered the compressed force mainly. The fiber did not offer resistance, basically, as it was with vulnerable rigidity. Other fibers in different direction had the ability to prevent crack from transverse extension, they can also improve compressing strength and toughness of concrete, consume a certain amount of energy. Nevertheless, the reinforced range was smaller than the tensile state and flexural state.The reason why basalt fiber can perfect mechanical property of concrete was benefited from crack resistance mechanism of fiber. On the premise of excellent fiber dispersion, basalt fiber contributed to the volatilization for extra water of concrete, the formation of cavities in concrete was prevented or reduced. Meanwhile, basalt fiber with fine dispersion conquer stress concentration phenomenon due to compress, air shrinkage, and other effects, then it can stop micro crack from more extension or formation which contribute to relieving the space to form, extend crack to damage situation improving the mechanical property of concrete.However, what is worth mentioning that each mechanical property parameters show a trend of increasing first and then decreasing with the increase of basalt fiber volume content no matter the strength, toughness, or dissipation. According to the existing theoretical results, while there was relatively low content volume of fiber, so, the force to extent speed of crack for basalt fiber would be restricted; On the contrary, while there are relatively high content volume and terrible dispersion in the concrete for basalt fiber which can be easily caused lump and then formed certain holes, at the same time, the bonding performance between fiber and concrete would be greatly weakened leading to a poor effect on improvement.(1)The optimum volume fraction of basalt fibers is 0.3% and 0.4% within the scope of this study. In this case, the compressive strength, tensile strength, flexural strength, toughness index, fracture energy, flexural-compressive ratio, and reinforcement coefficient of concrete are significantly improved. With the volume fraction of basalt fiber exceeding the optimum volume fraction, the mechanical properties of basalt fiber are weakened.(2)By comparing with the tensile strength and bending strength, there was no significant improvement in compressive strength. In other words, the incorporation of basalt fiber can improve tensile strength and bending strength more than compressive strength.(3)The failure mode of concrete can be changed by the incorporation of basalt fiber from brittle failure to non-brittle failure. In addition, by observing the failure characteristics of fibers at the failure section, it can be judged that there is a good bonding behavior between basalt fiber and concrete.(4)The compressive toughness, the tensile toughness, and bending toughness of BFRC were evaluated by the advanced evaluation method of toughness, Hillerborg characteristic length, and fracture energy, respectively. It indicated that the incorporation of basalt fiber was an adoptable way to improve the toughness of concrete performance and crack resistance.Compared with the compression, tensile, bending test of BFRC and plain concrete, the following conclusions were obtained:


In univariable analyses, chronic graft-versus-host-disease (cGvHD) (OR 3.07; 95% CI 1.34–7.07; The majority of allo-HSCT survivors were on SL 1 year after treatment, and cGvHD, low vocational satisfaction and depressive symptoms were associated with full-time SL 1 year after allo-HSCT.Healthcare professionals need to be observant of and manage the consequences of cGvHD and patients’ symptoms of depression in order to support them appropriately in their return-to-work process. An allogeneic haematopoietic stem cell transplantation  is a procedure where healthy haematopoietic stem cells from a donor are infused to a recipient to replace stem cells that are defect from the underlying disease or treatment in the hope that the recipient will recover the ability to produce their own healthy haematopoietic stem cells. Prior to allo-HSCT, patients receive chemotherapy and/or radiation therapy in order to suppress their underlying malignancy and facilitate the engraftment of the new stem cells . It is aResearch has shown that factors associated with a lower likelihood of RTW for allo-HSCT survivors include female gender, older age, poorer health and worse physical functioning , 7 along. Hence, the aim of this study was to examine SL 1 year after allo-HSCT and its association with demographic, medical, and psychological factors, together with vocational and financial satisfaction.Long periods of sick leave (SL) can have a negative impact on areas such as health, work, social relationships and financial situation causing changes in self-image, feelings of exclusion and social stigma –25. The This is a longitudinal, prospective single-centre study using data collected at the time of allo-HSCT, 7 months and 1 year after allo-HSCT.n = 84) either declined participation or were not invited to participate. The reasons for the latter were not recorded but are likely to have been due to the staff being too busy or the patient too sick. At baseline, 237 questionnaires were handed out and 194 responded (82% response rate). Only those who responded to the questionnaire at all three time points (n = 136) and did not report early retirement or disability pension (n = 14) at any time point were included (n = 122).All consecutive adult patients admitted for allo-HSCT between March 2009 and January 2016 were screened, and those fulfilling the inclusion criteria were approached. Inclusion criteria were haematological disease, age 18–65 years, able to understand Swedish and living in Sweden  . The scaLife satisfaction was measured using the validated Life Satisfaction Checklist-11 (LiSat-11) . Two itet tests or two-sided χ2-tests depending on the data level. Missing data in instruments based on sum scores, i.e. HADS, were replaced using person-mean imputation [p < 0.05. Factors analysed were demographic , medical , psychological (symptoms of anxiety and depression) and satisfaction with vocational and financial situation. A multivariable logistic regression was then performed where all factors with a p value ≤ 0.05 in the univariable analyses were included. The statistical calculations were conducted using SPSS 24.0 .Potential statistical differences between baseline respondents and non-respondents were analysed using either independent putation  if missiputation . Odds ran = 194) and non-respondents (n = 43) regarding age and diagnosis, but a statistically significant difference was found regarding gender with females participating to a higher degree (X2(1) = 4.6, p = 0.03).There were no statistically significant differences between baseline respondents , part-time SL (1–75%) or no SL from pre-diagnosis to 1 year after allo-HSCT can be seen in Fig. p = 0.01), having symptoms of depression at 7 months  and low levels of satisfaction regarding vocational situation at 7 months  (Table p = 0.01) and having symptoms of depression at 7 months   [Examination of SL during the first year after allo-HSCT revealed that almost all participants were on full-time SL at the time of allo-HSCT and although the percentage decreased over time, 39% were still on full-time SL 1 year after treatment. No studies investigating SL after allo-HSCT were found with which to compare the present results. However, a longitudinal study found that of patients who had undergone an autologous HSCT due to relapse after treatment for lymphoma, 30% remained on SL after the first year (part- or full-time SL unknown) (n = 164) . Severaln = 164) , 7, 33. n = 164) .Comparing allo-HSCT patients with other cancer diagnoses can be problematic, as treatment regimens vary considerably, but studies have revealed that chemotherapy can significantly prolong SL and delay RTW –37. HoweAn explanation for the high proportions of being on SL in this study could be that clinicians recommend all allo-HSCT patients to take full-time SL for at least 6 months unless they can easily adapt their employment to reduce the risk of becoming infected with, for example, community acquired respiratory viruses such as influenza and respiratory syncytial virus. This recommendation is prolonged if at 6 months post-treatment a patient is still on full immunosuppression for GvHD. This is a unique situation not applicable to most other cancer patients, and the current Covid-19 pandemic has only increased the need for this type of self-protection from respiratory viruses in allo-HSCT patients .None of the demographic factors investigated in this study were associated with full-time SL 1 year after allo-HSCT. However, sociodemographic factors have previously been shown to be associated with SL and RTW. In a large study including different types of cancer diagnoses, higher age and lower education predicted longer SL , while sThe medical factor cGvHD was significantly associated with full-time SL 1 year after allo-HSCT both in univariable and multivariable analyses, which is not surprising and in agreement with two earlier studies focusing on RTW , 11. PreThe present results show that having symptoms of depression at 7 months after treatment, but not at baseline, was associated with full-time SL 1 year after allo-HSCT. No previous studies have been found that specifically explore associations between depression and SL after allo-HSCT. However, although it is known that depression negatively affects RTW after injury or illness in general , this haA factor associated with SL in the univariable analysis was low vocational satisfaction at 7 months, but not at baseline, after allo-HSCT. This is in line with studies of breast cancer patients, where low vocational satisfaction 6 weeks post-surgery predicted non-RTW 10 months after surgery . Also, sA strength of this study is the inclusion of longitudinal data and a relatively large sample size, considering that approximately only 400 allo-HSCT are performed annually in Sweden. However, it is still possible that a larger sample size might have yielded different results. A limitation is the lack of information regarding SL of those who were not invited to participate, especially as the reasons for not being included are unknown. Another strength is the use of clinically diagnosed cGvHD data, as many other studies only use self-reported data, which could be considered uncertain due to subjectivity. The lack of participants diagnosed with severe cGvHD means that those most affected by cGvHD were not included, possibly because they either dropped out or died. In the logistic regression analyses, the presence rather than the severity of cGvHD was analysed, which could have influenced the cGvHD results. However, analyses of the severity of cGvHD were also performed and showed similar results. In addition, the likelihood of participants being classified as having symptoms of depression might be overestimated in this study since symptoms of depression were measured using the HADS self-assessment scale and not diagnosed by a clinician. However, HADS has been found to have excellent case finding abilities in many settings . In thisIn conclusion, this study appears to be the only study examining SL and factors associated with full-time SL 1 year after allo-HSCT. The results show that a large proportion of allo-HSCT survivors are still on full-time SL 1 year after treatment and that cGvHD and depressive symptoms may be associated with SL. These results suggest that it is important for health care staff to closely monitor and manage the consequences of cGvHD and be observant of and find appropriate care strategies for patients’ symptoms of depression in the aftermath of allo-HSCT to increase the likelihood of a successful RTW.


The composites are synthesized by in situ polymerization of styrene in the presence of POSSs and characterized by 1H-NMR. The characteristics of thermal parameters are determined using kinetics literature methods, such as those developed by Kissinger and Flynn, Wall, and Ozawa (FWO), and discussed and compared with each other and with those obtained in the past for similar POSS/PS composites. A good improvement in the thermal stability with respect to neat polymer is found, but not with respect to those obtained in the past for polystyrene reinforced with single- or double-POSS cages. This behavior is attributed to the greater steric hindrance of the three-cages POSS compared with those of single- or double-cage POSS molecules.A comprehensive kinetics degradation study is carried out on novel multiple cages polyhedral oligomeric silsesquioxane (POSS)/polystyrene (PS) composites at 5% ( Daily life is characterized by the constantly growing use of objects and devices made of plastic. Simple carbon-chain polymers, such as polyolefins ,2, repreon atoms . The abion atoms , carbon on atoms , and nanon atoms ,32, makeon atoms . Particuon atoms ,35 and ton atoms .Composites of PS and multiple-cage POSS were synthesized by in situ polymerization of styrene in the presence of 5% molecular filler, and the following compounds were obtained:T5%) and apparent activation energy (aE) of degradation, were compared with each other and with those of the control PS to evaluate the differences in thermal behavior, if present.After a spectroscopic investigation aiming to verify the presence of POSS in the synthesized composites, the composites’ thermal behavior in terms of resistance to thermal degradation along with the rate of degradation were evaluated by means of thermogravimetric analysis (TGA) and kinetics literature methods ,38,39. TTetrahydrofuran (THF), toluene, styrene, 2,2-azobis (isobutyronitrile) (AIBN), trichloroisobutyllsilane, trichlorocyclopentylsilane, p-tolyltrichlorosilane, and methanol were acquired from Aldrich Co. . The latter four chemicals were used as received, whereas the other ones were treated as follows prior to use: THF was distilled over a Na-benzophenone mixture); toluene was stirred over calcium hydride for a day and then distilled in a nitrogen flow; styrene was purified in an inhibitor removal column; AIBN was crystallised from dry ethanol in a dark setting at room temperature. Cyclopentyl trisilanol POSS was prepared in agreement with literature reports ,41, wher1H NMR characterization are reported in our previous study [The synthesis procedure of 4-methyl phenyl (trioxyisobutyl POSS) silane and 4-methyl phenyl (trioxycyclopentyl POSS) silane together with their us study  and the 1 and 2 were obtained by in situ polymerization mixing in toluene 5% (w/w) of 4-methyl phenyl (trioxyisobutyl POSS) silane and 4-methyl phenyl (trioxycyclopentyl POSS) silane, respectively, with styrene. After the dissolution of each POSS and styrene monomer in toluene, the AIBN radical initiator was added to the mixture before being frozen in a liquid nitrogen bath, degassed with a vacuum pump, and then thawed. This operation was repeated three times before sealing under vacuum and heating, under stirring, at 343 K for a day. After this time, the obtained solution was precipitated by adding methanol and collected by filtration. The compounds were dried under vacuum at 313 K obtaining a yield of 76.6% and 83.2%, respectively, for samples 1 and 2.Samples 1H-NMR characterization was performed in a Unity Inova instrument 1H 500 MHz  by using deuterochloroform (CDCl3) as a solvent and tetramethylsilane (TMS) as an internal standard.−3 g were placed in an alumina open pan and degraded at eight different heating rates , in the temperature range of 298–973 K. Thermal degradations were performed in flowing nitrogen (0.02 L∙min−1), whereas thermos-oxidative degradations were performed in a static air atmosphere. TGA-obtained data were used to plot the percentage of an undegraded sample, (1 − D)%, as a function of temperature, where D is equal to:W0 and W are the masses at the starting point and during the TGA experiment, respectively. The derivative of the TG (DTG) curves were used to evaluate the temperature at the maximum degradation rate (mT), which was then used for kinetics calculation. All the considered T values were averaged over three runs, the maximum difference between the average and the experimental values being within ±1 K.TGA was carried out with DTG-60 equipment . Before performing measurements, the TGA apparatus was calibrated in agreement with a consolidate procedure reported in the literature ,44 using−1 with a resolution of 4.0 cm−1.The residues derived from TGA were analyzed by FTIR with a Spectrum 100 spectrometer  directly, without any pre-treatment, using a universal attenuated total reflection (ATR) sampling accessory. The spectra were collected at room temperature from 4000 to 650 cmw/w) due to the formation of methanol soluble oligomers of PS. For this reason, before subjecting our samples to thermal characterization, we performed 1H-NMR measurements to verify the exact POSS content in the prepared PS composites. POSS content was calculated at 6.2% and 7.5% for compounds 1 and 2, respectively, considering the ratio between the POSS hydrogen atoms and the PS hydrogen atoms.During the in situ polymerization, we observed a slight increase in the POSS content in the obtained composites with respect to the initial mixture ratio  in oxidative conditions .The least square treatment of the data reported in aE values through the straight lines obtained reporting ln(Φ/mT2) as a function of 1/mT at various heating rates. In Equation (1), Φ is the heating rate, mT is the temperature at maximum rate of weight loss, n is the apparent reaction order, R is the universal gas constant, A is the pre-exponential factor, and mW is the weight of the sample at the maximum rate of mass loss. The Kissinger equation yields reliable aE values only when conversion does not practically vary the heating rate, and it should not be considered an isoconversional method [αT is the temperature when, at a fixed heating rate Φ, a certain conversion α is achieved.The Kissinger Equation,l method ,46,47. TaE values obtained by the Kissinger equation, together with their corresponding regression coefficients, are reported in Degradation Eα) were obtained by the FWO equation through the ln(Φ) vs. 1/αT plots reported in Activation energy values at a fixed value of conversion  and (2) was found, showing a large enhancement for the composites reinforced with the multiple-cage POSS in static air atmosphere, amounting approximately to 20–25 kJ·mol−1. Conversely, in an inert environment, the average (among the Kissinger and FWO methods) degradation aE values showed a lesser increase with respect to the value of the control PS, about 10–15 kJ·mol−1. Kinetics data confirmed the key role of multiple-cage POSS in the thermo-oxidative degradation process of the obtained PS composites that let down the degradation rate, and, as demonstrated by the T5% values, enhanced the overall thermal stability of the composites. In an inert environment, the role of POSS seems to be to mitigate, even if, in any case, there is a slight slowdown of the degradation kinetics (As shown in kinetics .−1 lower than in the systems studied in the past. This behavior could be attributed to the difficulty of obtaining multiple-cage POSS, which are sterically bulkier than single-cage POSS, to disperse themselves in the polymer matrix. In addition, the same steric hindrance can likely lead to a reduced level of interaction with the matrix, which can be translated into a reduced reinforcement action.When we looked at our previous research regarding the kinetics of the degradation of similar PS/POSS composites but with single- ,50,51 orThe design and preparation of new PS composites reinforced with triple-cage POSS, uniquely functionalized with isobutyl and cyclopentyl groups, were carried out to verify if the presence of a higher number of POSS cages in the same molecule, dispersed in the matrix, leads to a further increase of material stabilization.The kinetics study of the thermal and thermo-oxidative degradations of the prepared composites and the control polymer showed an increase in the thermal stabilization of the obtained materials. However, this was not comparable with the results obtained in the past for similar systems obtained by adding molecules with one or at least two POSS cages to the matrix.We attribute this result to the increase in the steric hindrance of the multiple-cage POSS that leads to dispersion difficulty at the molecular level in the polymer matrix, reducing the level of interaction and thus the reinforcement action.


Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care.A quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018.Overall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use , and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018.Multifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care. Strategies to limit inappropriate antibiotic use and spread of drug-resistant microorganisms have become an increasing priority for health policies and services. Overuse of antibiotics for unnecessary conditions not only promotes antibiotic resistance and loss of protective flora, but also increases the likelihood of preventable drug-related adverse events as well as high costs for Health Care Services ,2. AlthoExisting evidence suggests that among strategies aimed to decrease prescription rates of antimicrobials in Primary Care those based on multiple approaches were the most effective –13. WhenIn the absence of regional or national reference guidelines addressing the most common infections in the community on the websites of Clinical Practice Guidelines of the Andalusian Health Service (AHS)  or of thThe guide met several requirements to be used as a resource in programs for optimizing the use of antimicrobials: rigorous on development and editorial independence (met AGREE criteria ), reliabThe aim of this study was to assess the impact of “The Aljarafe Antimicrobial Therapeutic Guide” publication, and subsequent interventions aimed at improving antibiotics prescribing in the Andalusian Primary Health Care setting. Interrupted time-series analysis (ITSA) was used to determine whether there was a significant change in antibiotic prescribing rates and trends after interventions.We conducted a quasi-experimental study in the Primary Health Care setting, with ITSA. Initially, interventions aimed at implementing the guide were planned to be carried out at the local level at the Aljarafe Primary Health Care Area . However, shortly thereafter, the AHS adopted the guide as a reference for the implementation of programs to improve the use of antimicrobials in the whole Andalusian Public Health Care System . Then, AHS carried out activities to implement the guide throughout the whole region. Further, the guide was incorporated into the website of the Clinical Practice Guidelines in the Spanish National Health System, Guiasalud  in 2011,From 2009 to 2011, a multidisciplinary team composed by individuals from all relevant professional groups  developed the antimicrobial guide for the treatment of infectious diseases and prophylaxis in the community . The guiInterventions aimed at disseminating the guide started on 2011, just after the publication of the first edition in both, book and electronic format. The second edition, was published online in 2012, and included safety alerts associated with antimicrobials. The third edition, published online, was undertaken to revise all the recommendations. The update resulted in the recommendation of more restrictive use of antibiotics (mainly of broad spectrum antibiotics) and shorter antibiotic therapies than earlier versions, in line with new evidence. The third edition was published by chapters as they were being updated. This process began in 2016, and was completed in 2018.S1 Fig).Interventions carried out following the delivering of the guide at the regional level included: educational meetings, and institutional training workshops on ASP for general practitioners, paediatricians, dentists, and primary care pharmacists, the development and selection of indicators for continuous monitoring of antimicrobials , monthlyThe guide was applicable in Primary Care , in hospital emergency rooms, and in nursing homes, to treat ambulatory patients with infectious diseases.Aggregated antibiotic prescribing data (ATC J01 class) were extracted from the computerised pharmacy records of dispensed drugs, reimbursed by AHS. Authors accessed aggregated data, meaning that individual patients could not be identified. Antimicrobial consumption rates were expressed into defined daily doses (DDD) per 1,000 inhabitants-days (DID) by using the DDD in force until the end of the study. Population data were obtained from the National Statistics Institute database .Consumption of the following classes of antibiotics was measured: overall rate of antibiotic prescribing  (this indicator was included in pay-for performance programs by the AHS from 2013); DID beta-lactam antibacterials, penicillins (J01C); DID other beta-lactam antibacterials, cephalosporins (J01D); DID quinolones (J01M); DID macrolides, lincosamides and streptogramins (J01F) , and DID amoxicillin and betalactamase inhibitor, amoxicillin clavulanate (J01CR02). When we refer to broad-spectrum antibiotics, we refer to amoxicillin clavulanate, quinolones and 3rd generation cephalosporins. Penicillins, amoxicillin, macrolides, or nitrofurantoin are considered narrow-spectrum antibiotics. Data for each year were collected during the following year.actest. A p-value less than 0.05 was considered significant.The study ran from January 2004 until December 2018. A sensitivity analysis was done to choose the best cut point of trends in terms of antibiotic prescribing rates. ITSA was carried out using various time points, including 2010, 2011, 2012, and 2013, for the total consumption of antibiotics in both series, Aljarafe and Andalusia. This led as to identify 2011 as the turning point, i.e. the time when a change in trends in total antibiotic prescribing rates was observed. Prescribing data were collected over 7 years pre-interventions (baseline) and 8 years post/during interventions. We conducted ITSA to determinate whether there was a measurable change in level and/or trends of antibiotic prescribing rates after interventions. ITSA was conducted with “ITSA module” of Stata Programme, which produces Newey-West standard errors for coefficients estimated by ordinary least squares regression . GradienAlternatively, we estimated the effect of interventions by calculating absolute and relative differences between predicted values, expected if interventions had not happened, and observed values. These differences were calculated in 2018, seven years after starting the interventions (2018).Statistical analysis was performed using Stata v.14 .This research was conducted in accordance with the Declaration of Helsinki and national and institutional legislation in Spain regarding clinical research and personal data protection. It has been approved by the Ethics Committee on Health Research of the Hospital Virgen del Rocío  (Codes 2010PI/14 and 2012PI/171).The absolute number of annual DDD antibiotic prescriptions ranged, during pre-intervention period from 2,042,280 in 2004 to 2,750,132 in 2011 in the Aljarafe Area, and from 54,575,612 in 2004 to 64,475,525 in 2011 in Andalusia. Seven years after starting the interventions, DDD prescriptions decreased to 2,078,057 in the Aljarafe Area and to 50,190,292 in Andalusia. Population size increased in this period of time both in Aljarafe  and Andalusia .The overall annual antibiotic DID in Primary Care ranged from 17.89 (in 2004) to a maximum of 20.43 (in 2011) in the Aljarafe Area. In Andalusia, annual antibiotic DID ranged from 19.65 (in 2004) to a maximum of 20.97 (in 2011). Overall, the annual antibiotic prescribing rate dropped by 28% in the Aljarafe Area and 22% in Andalusia, between 2011 and 2018.The most frequently prescribed antibiotics in 2004 were penicillins, and specifically amoxicillin clavulanate, followed by quinolones, cephalosporins, and macrolides.Penicillins prescribing rates increased in the pre-intervention period, both in Aljarafe and in Andalusia. Penicillins DID ranged from 12.57 in 2004 to 16.08 in 2011 in Aljarafe, and from 12.38 in 2004 to 14.89 in 2011 in Andalusia. Total penicillins prescribing dropped by 33% in Aljarafe and 25% in Andalusia between 2011 and 2018. Rates of amoxicillin clavulanate changed as follows: they ranged from 7.29 DID in 2004 to 9.76 in 2011 in Aljarafe, and from 8.44 in 2004 to 10.19 in 2011 in Andalusia. Amoxicillin clavulanate DID dropped by 58% in Aljarafe, and 49% in Andalusia between 2011 and 2018.Quinolones, macrolides, and cephalosporins prescribing rates decreased in the pre-intervention period, both in Aljarafe and Andalusia. Quinolones DID dropped by 51% in Aljarafe and 30% in Andalusia between 2011 and 2018. Cephalosporins DID dropped by 16% in Andalusia between 2011 and 2018. No changes in Aljarafe were observed between these two years. Macrolides DID increased 14% in Aljarafe and 7% in Andalusia between 2011 and 2018. Prior to interventions, trends of overall antibiotic prescribing rates showed a significant increase of 0.19 DID per year in the Aljarafe Area, and a non-significant increase of 0.15 DID per year in Andalusia between 2004 and 2011 (Table 2). Trends of total penicillins and amoxicillin clavulanate prescribing increased in the pre-intervention period, both in Aljarafe and Andalusia. Trends in rates of quinolones, cephalosporins, and macrolides decreased in this period, both in Aljarafe and Andalusia .ITSA is shown in Fig 1). Compared with the expected antibiotic prescriptions, based on pre-intervention trends, we observed reductions in DID, at the end of the study period for overall antibiotic prescribing , penicillins , amoxicillin clavulanate , and quinolones  (Table 2).Following the start of interventions, there were significant changes in trends of antibiotic rates with a decline over time in overall antibiotic DID, penicillins DID, and amoxicillin clavulanate DID, a stronger decline in quinolones DID than that observed during the pre-intervention period, a slower decline in cephalosporins DID than that observed during the pre-intervention period. Finally, there was an increase in trends of macrolides rates, both in Aljarafe and Andalusia between 2011 and 2018 (Table 2), although cephalosporins rates decreased during the post-intervention period.Rates of cephalosporins and macrolides were higher than that expected if the interventions had not happened  provides better health outcomes, less patient safety issues, and less antimicrobial resistance development.The guide was the core element of the strategies. The development of high quality, reliable guides with several functionalities , a relatively simple method to influence many prescribers, seems to play a crucial role. Health professionals need reliable and independent antimicrobial guides to improve quality prescribing and fight some barriers for making the best decisions for their patients with infections. However, just delivering guidelines is not usually enough to achieve major changes ,34,35. Iet al did not achieve any reduction in antibiotic prescribing rates after the implementation of antimicrobial guidelines, coupled with feedback on individual antibiotic prescribing [The size of the effect of the interventions varies considerably and, once several interventions are implemented simultaneously, it is difficult to differentiate the impact of each strategy . We can scribing . In our scribing , althougThis study was large, including a complete geographical region and all prescriptions dispensed from general practitioners, paediatricians and dentists of a Public Health Care Service, thus providing a complete picture of overall antibiotic prescribing in Primary Care. Our findings may be applied to other health services with the same characteristics. On the other hand, we have monitored the impact of interventions of a long enough period of time to establish the sustainability of the effects.There are several study limitations. Firstly, this is a quasi-experimental study without a control group. We cannot exclude the possibility that factors other than these interventions could influence antibiotic prescribing during the period of the study. To overcome this limitation, we performed an ITSA. ITSA is arguably the strongest quasi-experimental research design and is particularly useful when a randomized trial is infeasible or unethical. Due to the few time points, our results should be interpreted with caution as they may be underpowered. Although we did not have a control group, the availability of national data ,33 allowSecond, the data refer to the prescriptions made in Primary Care of the Public Health Service. There has been no follow-up of the prescriptions to outpatients by Hospital prescribers, where the interventions have not been made.Third, we assumed a good therapeutic compliance, and that the actual consumption of antibiotics corresponded to the dispensations made.Finally, we cannot know the actual level of use of the guide in our setting, since one cannot know the number of queries in the book format or the number of downloads in all electronic platforms where it is uploaded. With regard to the electronic version, we cannot differentiate queries that have been made in our setting and those that have been made from other settings.Being aware of limitations, this study shows that multifaceted and continuous interventions following the delivering of a rigorous, reliable, and accessible antimicrobial guide led to significant and sustained reduction in overall antibiotic prescribing in Primary Care, mainly due to the reduction in penicillins prescribing , and other broad-spectrum antibiotics such as quinolones and cephalosporins. This sustained decrease probably resulted from the additive effect of successive interventions maintained over time, with a great institutional support, enabling the incorporation of guide recommendations in everyday clinical practice by a large number of professionals. As the benefit of the interventions reverts after they ceased ,34,41, wThese findings have important implications for the Spanish National Health System, given the very high prescription rates of antimicrobials and resistances in our country, compared to those from other European Union countries ,42. One In conclusion, multifaceted interventions following the delivery of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could lead to sustained improvement in antibiotic prescribing in Primary Care. Which specific elements that must be added to multiple strategies at the local setting, will depend on the initial situation, resources, and institutional support without losing sight of the fact that, before starting programs, it is important to know which strategies can be supported by institutions for long-term.S1 Fig(PDF)Click here for additional data file.S1 Data(XLS)Click here for additional data file.


Background: Although there are multiple ways to manage immunoglobulin G4–related disease (IgG4-RD), including treatment with glucocorticoids, “steroid-sparing” immunosuppressive drugs, or biologic agents, few clinical trials on IgG4-RD have been conducted. This study aimed to compare the efficacy and safety of glucocorticoids (GCs) combined with cyclophosphamide (CYC) or mycophenolate mofetil (MMF) in IgG4-RD patients. This cohort study was registered at ClinicalTrials.gov (ID: NCT01670695).Methods: This retrospective study included 155 IgG4-RD patients who received GCs with CYC or MMF at the Department of Rheumatology at Peking Union Medical College Hospital between January 2012 and July 2018. Propensity score matching (PSM) was conducted to match two groups of patients based on their baseline clinical characteristics. Treatment response, relapse rate, and drug safety were analyzed. The treatment response was evaluated based on complete response (CR), partial response (PR), and no change (NC), and the cumulative relapse rate and adverse events in each treatment group were compared using Kaplan–Meier curves and log-rank test, respectively.Results: Of the 155 IgG4-RD patients, 90 were treated with GCs plus CYC (group I) and 65 with GCs plus MMF (group II). After propensity score–matched (PSM) analysis, 108 patients were selected (54 in each group), 49 of whom had “definite” IgG4-RD, 8 “probable” IgG4-RD, and 51 “possible” IgG4-RD. At the last follow-up, the total response in groups I and II was 98.15 and 96.3%, respectively, and within 12 months, the cumulative relapse rate in group II was significantly higher than that in group I . Recurrence occurred at the paranasal sinus, lacrimal glands, skin, lung, pancreas, and bile ducts, and the relapsed patients achieved remission after switching immunosuppressants or/and increasing the GC dose.Conclusions: In IgG4-RD patients with internal organ involvement, GCs plus CYC or MMF are both effective with similar effects in disease response, while GCs plus CYC reduced the relapse rate better than GCs plus MMF. Immunoglobulin G4–related disease (IgG4-RD) is a systemic fibroinflammatory condition that affects multiple organs including the pancreas, bile duct, lacrimal gland, salivary gland, thyroid, lung, liver, gastrointestinal tract, kidney, and retroperitoneum . It is cGlucocorticoids (GCs) are the first-line therapy for achieving clinical remission in active or untreated IgG4-RD patients . RelapseMMF, an immunomodulatory agent with antifibrotic effects, can be used for the treatment of IgG4-RD because of its ability to inhibit the transforming growth factor beta pathway . CYC is This prospective observational cohort study to investigate the disease course and treatment response of IgG4-RD patients was registered on ClinicalTrials.gov (ID: NCT01670695). From January 2012 to July 2018, consecutive patients treated with GCs plus CYC or MMF were retrospectively identified for this study. The study protocol was approved by the ethics board of Peking Union Medical College Hospital, and all study subjects provided written informed consent for study participation.The inclusion criteria were as follows:18 to 75 years of age.Agreement with the 2011 comprehensive diagnostic criteria for definite, probable, or possible IgG4-RD as follows: (1) characteristic diffuse/localized swelling, sclerosis, or inflammation affecting single or multiple organs; (2) elevated serum IgG4 concentrations (135 mg/dL); (3) increased number of lymphocytes, infiltrated IgG4+ plasma cells (IgG4+ cells/IgG-positive cells >40% and >10 IgG4+ plasma), and fibrosis. Patients who met criteria (1), (2), and (3) were diagnosed with definite IgG4-RD; those who met (1) and (3) were diagnosed with probable IgG4-RD; and those who met (1) and (2) were diagnosed with possible IgG4-RD .Presence of internal organ involvement.Use of GC and CYC or MMF for initial treatment and maintenance until the 12-month follow-up.Regularly followed up at months 1, 3, 6, and 12.The exclusion criteria were as follows:Presenting only with IgG4-related dacryoadenitis and sialadenitis or lymphadenopathy of IgG4-RD.Serious infection.Presence of other rheumatic diseases.Presence of malignant diseases.Women with childbearing potential or currently planning a pregnancy.All patients underwent laboratory tests for complete blood count, erythrocyte sedimentation rate (ESR), hypersensitivity C-reactive protein (hs-CRP) levels, serum immunoglobulin, and IgG subclass concentrations, urinalysis, liver, and renal function tests; and at least one imaging examination, including ultrasonography, digital radiography (DR), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography/computed tomography (PET-CT). In total, 78 patients (72.22%) underwent CT scan, 24 (22.22%) underwent PET scan, 33 (30.56%) underwent MRI, and 49 (45.37%) underwent other imaging examinations, including ultrasound and DR. When necessary, tissue biopsies were analyzed and reviewed by pathologists using previously described methods , and labClinical features, laboratory results, imaging data, adverse events, and details of treatment protocol and disease relapse were evaluated at baseline and at 1, 3, 6, and 12 months after treatment or until relapse.Disease activity per visit was assessed by the IgG4-RD responder index (RI), with a system score of 0–4 for each site/organ system . An IgG4Three categories of clinical response were defined: (1) complete response (CR), in which IgG4-RD RI <3 and declined ≥2 points after treatment; (2) partial response (PR), in which IgG4-RD RI declined ≥2 points after treatment but still remained ≥3, and if IgG4-RD RI was 3 at initial treatment a partial response was defined as a 1-point decline after treatment; and (3) no change (NC), in which there was no significant improvement in affected organs and clinical symptoms and change of IgG4-RD RI <2 points , 9, 15.Relapse was defined as the recurrence of worsened/new disease manifestations or abnormality of organ-specific imaging findings despite treatment, with or without elevated serum IgG4 .t-test, whereas categorical variables were compared by the chi-square test, Fisher Exact test, or Mann–Whitney test. The Kaplan–Meier curves and log-rank test were used to calculate the cumulative relapse rate. Statistical analyses were performed using IBM SPSS statistics .Continuous variables are presented as mean ± standard deviation (SD), median, or interquartile range (IQR), and compared by p < 0.05), pancreas , and bile duct  involvement.From January 2012 to July 2018, 155 IgG4-RD patients who conformed to the inclusion criteria were selected. Among them, 90 were treated with GCs plus CYC (group I) and 65 were treated with GCs plus MMF (group II). Compared to group I, patients in group II had more paranasal sinus . In group I, patients received CYC at a mean initial dose of 54.75 mg/day . They maintained the initial dose for 3 months, after which it was reduced to 50 mg per day or every other day, consistent with previous treatment regimens  analysis to match group I patients with group II patients based on gender, age, involvement organs , and other involvement and constitutional symptoms not attributable to the involvement of a particular organ . At the end of the analysis, 108 patients were selected (54 in each group), of whom 49 were diagnosed with definite IgG4-RD , 8 with probable IgG4-RD , and 51 with possible IgG4-RD . In the post-match model, the differences of baseline characteristic between group I and group II was not statistically significance. All patients were treated with prednisone, which was gradually tapered down according to the individual's clinical response. The analyses indicated that the initial prednisone dosages were similar between the two groups  , and 2 had recurrence in the 12th month . In group II, recurrence at the paranasal sinus, lacrimal glands, skin, lung, bile ducts, and pancreas accounted for 25, 50, 12.5, 12.5, 12.5, and 25%, respectively, with the lacrimal glands being the most vulnerable to recurrence. The cumulative recurrence rate in groups I and II was 3.7 and 14.8%, respectively, and group II had a higher relapse rate than group I (= 0.046) .The follow-up data after retreatment in these 10 patients showed that they all achieved remission after the immunosuppressants were changes and/or the dose of GCs was increased according to their condition. In group I, for one patient, we increased the GCs dosage and replaced CYC with MMF, whereas for the second patient, the GCs dosage was increased. Of the 8 relapsed patients in group II, the treatment was converted to GCs and CYC for 3, iguratimod was added for 1, GC dose was increased and MMF was replaced with MTX for 1, and previous regimens with increased dosages were maintained in 3 patients. The details of relapsed patients in group I and group II are shown in Based on comprehensive assessment of disease response, relapse rate, and adverse reactions, it was suggested that GCs plus CYC had a better therapeutic effect than GCs plus MMF .Several immunosuppressants have been used as a steroid-sparing treatment for IgG4-RD, but there has been no head-to-head study comparing the efficacies between steroid-sparing drugs. In this retrospective cohort study, we aimed to explore the efficacies of GCs plus MMF therapy and GCs plus CTX and compare them in order to determine a better therapeutic strategy for IgG4-RD patients and prevent disease recurrence.In this study, CYC and MMF were used because their efficacies in IgG4-RD had been proven in previous studies. In a recent study, CYC plus GCs yielded a lower relapse rate and higher response rate relative to GC monotherapy. Similar to the results of combined CYC regimens, a study from India showed clinical improvement in patients who were treated with GCs plus MMF, with no case of relapse within a median duration of 8 months. Furthermore, an RCT study from China reported that GCs plus MMF was more effective than GCs monotherapy.In our study, IgG4-RD patients responded well to GCs plus CYC or MMF, and a majority of them experienced marked improvements within a month of treatment, which were manifested as improvement in the affected organs; reductions in the concentrations of serum ESR, CRP, IgG, and IgG4; as well as successful GC tapering. Both combined treatment regimens were efficient for IgG4-RD patients, having almost the same response rate during a year follow-up period. Comparing the ability of the two immunosuppressants to prevent flare by relapse rate, our results demonstrated that 10 patients (2 with CYC and 8 with MMF) relapsed, and relapse occurred earlier and more frequently in those receiving MMF than CYC (14.8 vs. 3.7%). Additionally, patients receiving CYC had less cumulative GCs than those receiving MMF, indicating that the steroid-sparing effect of CYC is superior to that of MMF. Therefore, the combined treatment with CYC decreased organ recurrence and maintained disease remission much better than combined treatment with MMF. Therefore, it was suggested that a low-dose CYC combination treatment regimen might be a better choice than low-dose MMF therapy in IgG4-RD patients with multiple organ involvement.In a recent RCT study that enrolled IgG4-RD patients with multiple organ involvement, it was pointed out that lacrimal glands and paranasal sinus were most susceptible to recurrence in patients receiving low-dose MMF plus GCs . HoweverRegarding safety issues, since low doses of CYC and MMF were applied in this study, both drugs were well tolerated, and this is consistent with previous IgG4-RD studies. The main adverse reactions in the CYC or MMF groups were infections and gastrointestinal reactions, and they did not differ between both groups . PreviouSo far, this is the first study to compare the effects of different immunosuppressive agents in IgG4-RD, although there are some limitations. Since the study is a retrospective cohort study, unknown variables might affect the results, leaving room for potential bias such as adverse effects that were as retrieved from the patients' hospital records. However, the results are quite reliable because there were no statistically significant differences in the baseline characteristics between the two groups.In conclusion, most IgG4-RD patients had a good response to both treatment regimens, but GCs plus CYC had a lower rate of relapse within a year than GCs plus MMF. This suggests that GCs plus CYC might be a more effective treatment option for IgG4-RD patients with internal organ involvement. However, larger prospective and RCT studies are required to understand the role of CYC and MMF in IgG4-RD.All datasets generated for this study are included in the article/supplementary material.XL and YP designed the research, analyzed data, and wrote the manuscript. PZ, ZL, JL, and HL collected and analyzed data and revised the manuscript. XZh, FZ, and XZe optimized the research and proofread the paper. YF and WZ designed the study and wrote 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.


This paper investigated the static behaviour of glass fibre reinforced polymer (GFRP) built-up hollow and concrete filled built-up beams tested under four-point bending with a span-to-depth ratio of 1.67, therefore focusing their shear performance. Two parameters considered for hollow sections were longitudinal web stiffener and strengthening at the web–flange junction. The experimental results indicated that the GFRP hollow beams failed by web crushing at supports; therefore, the longitudinal web stiffener has an insignificant effect on improving the maximum load. Strengthening web–flange junctions using rectangular hollow sections increased the maximum load by 47%. Concrete infill could effectively prevent the web crushing, and it demonstrated the highest load increment of 162%. The concrete filled GFRP composite beam failed by diagonal tension in the lightweight concrete core. The finite element models adopting Hashin damage criteria yielded are in good agreement with the experimental results in terms of maximum load and failure mode. Based on the numerical study, the longitudinal web stiffener could prevent the web buckling of the slender GFRP beam and improved the maximum load by 136%. The maximum load may be further improved by increasing the thickness of the GFRP section and the size of rectangular hollow sections used for strengthening. It was found that the bond–slip at the concrete–GFRP interface affected the shear resistance of concrete–GFRP composite beam. Pultruded glass fibre reinforced polymer (GFRP) sections have shown potential application for bridges ,2,3,4, bTurvey and Zhang  found thWeb crippling could be effectively prevented by providing stiffeners at the web–flange junctions and infill for GFRP sections. Borowicz and Bank  showed tThere is limited research on shear behaviour of GFRP built-up hollow section and concrete filled beams. Some research has been conducted to study shear behaviour of concrete filled CFRP beams, hybrid concrete–GFRP beam and phenolic core-GFRP sandwich beams. Gautam and Matsumoto  studied This study investigated the shear behaviour of GFRP rectangular hollow and concrete filled built-up beams tested under four-point bending. Two parameters considered for hollow sections were longitudinal web stiffener and strengthening at the web–flange junction. Lightweight concrete was used as an infill to minimise weight gain. The experimental results indicated that hollow sections failed by web crushing at supports while concrete filled section failed by diagonal tension at the concrete core. Strengthening the web–flange junctions and concrete infill increased the maximum load of GFRP hollow sections. Finite element (FE) analyses adopting Hashin damage model achieved good agreement in terms of maximum load and failure mode compared to the experimental results. Finally, a parametric study was conducted to provide a better understanding of the effects of the thickness of GFRP sections and stiffness at the web–flange junction on the shear response of GFRP built-up beams. The parameters investigated were the size of C channel and square hollow sections (SHS), the thickness of the flanges, and the effectiveness of longitudinal stiffeners for GFRP beams with thinner webs.Four types of section prepared in this study are illustrated in 3 was used to produce the lightweight concrete with a density of 1600 kg/m3. The slump of lightweight concrete was about 100 mm. During concrete casting, the GFRP hollow section was fixed vertically as concrete was filled into the void. Three concrete cylindrical specimens with a diameter of 100 mm and 150 mm height were prepared and cured for 28 days at the ambient temperature. The 28-day average compressive strength of lightweight concrete was 12 MPa.The mix proportion of lightweight concrete is presented in The tensile strength of GFRP was determined based on ASTM standard . The couThe GFRP beams were tested under four-point bending with the experimental setup illustrated in Load versus displacement response of all GFRP beams are depicted in The control beam (S1) showed the lowest maximum load of 90 kN, followed by the hollow beam with longitudinal stiffener (S2) of 97 kN. The maximum load of the beam with SHS at corners (S3) was 132 kN, while the concrete filled beam (S4) showed the highest maximum load of 236 kN. The difference of maximum load between the control beam (S1) and the hollow beam with longitudinal stiffener was small (S2), less than 8%, and this implied that the longitudinal stiffener was ineffective in improving the load capacity as the web buckling was not the governing failure mode for the control beam. Damage initiated by web crippling (web crushing at the supports) for both the S1 and S2 beams. This could be attributed to the low compressive strength in the transverse direction as the glass fibre mainly aligned in the longitudinal direction due to the pultrusion process. As the displacement of actuator further increased, the adhesive bonding between webs and the bottom C channel failed as depicted in The maximum load of the beam with SHS at corners (S3) was 47% higher than the control beam (S1). The SHS improved the bearing capacity of the flanges as the thickness of the flanges was increased by 5 mm at the web–flange junction compared to the control beam. The use of SHS could also improve the rotational stiffness at the web–flange junction due to the higher rotational rigidity of SHS compared to the C channel. The study by Borowicz and Bank  showed tThe lightweight concrete infill improved the maximum load by 162%. Concrete infilled beam showed the highest load improvement among all the options considered. However, the lightweight concrete infill increased the weight of GFRP beam significantly. The concrete infill eliminated the web crushing of GFRP section as the concentrated force at the supports could be distributed to the concrete infill. This beam demonstrated brittle behaviour at the maximum load, and the damage is shown in The commercial finite element software, Abaqus, was used in this study. The GFRP beams were modelled using shell elements where different shell thicknesses were defined at the web–flange junctions to correctly model variation of web thickness due to joining C channels or SHS to the webs. The GFRP sections were discretised using four-node reduced integration shell elements (S4R) with a mesh size of 10 mm. In contrast, the concrete infill was discretised using eight-node reduced integration continuum 3D solid elements (C3D8R) with a mesh size of 20 mm. The loading cylinders and supports were modelled using solid elements (C3D8R) and assigned with elastic material properties. The surface to surface contact was used to model the interaction between the cylinders and the GFRP beams. For interaction between concrete infill and GFRP section, it was found that bond–slip and normal separation between GFRP webs and concrete infill should be considered in order to predict shear failure in the concrete infill accurately. Therefore, the surface to surface contact was used. A similar observation was reported for CFRP box beams filled with concrete , and con22, and σ12 are the effective stress tensors in the longitudinal, transverse, and in-plane shear. St,1 and Sc,1 denote the tensile and compressive strength in the longitudinal direction, St,2 and Sc,2 denote tensile and compressive strength in the transverse direction, while S12 and S23 denote shear strength in the longitudinal and transverse direction. α is a coefficient (either 0.0 or 1.0) to take into account the contribution of in-plane shear stress on the damage of fibre in tension. The default value of 0.0 was adopted in this study as the fibre tension failure was not critical for web crippling failure. Transverse compressive and in-plane shear strength governs the ultimate load of the GFRP section failed by web crippling [Hashin damage initiation criteria could be used to predict anisotropic damage in elastic-brittle materials such as GFRP by considering four different failure modes, namely (i) fibre tension  and (ii) ratio of the second stress invariant on the tensile meridian to the compressive meridian (Kc). The default values for these parameters are shown in Concrete damaged plasticity (CDP) model is a continuum, plasticity based damage model suitable for both plain concrete and reinforced concrete structures. It could be used to model concrete structures subjected to monotonic, cyclic and dynamic loading under low confining pressures. It considers isotropic damaged elasticity in combination with nonassociated multi-hardening plasticity in tension and compression to model irreversible damage of concrete during cracking and crushing. It assumes nonassociated potential plastic flow based on the Drucker-Prager hyperbolic function, which requires a definition of parameters such as dilation angle (ψ) and flow potential eccentricity (ε). For the dilation angle, a typical value of 31° was adopted in this study. From literature, a wide range of dilation angle, from 5°  has beenck and fcm are concrete characteristic strength and mean strength, respectively, k is the plasticity number, and η is The tensile strength (ode 2010 :(5)flctmTension stiffening was modelled using linear stress–crack opening relationship based on the fracture energy (GF) of lightweight concrete. For plain concrete or concrete with a low percentage of reinforcement, the specification of stress–strain relation for tension stiffening leads to mesh sensitivity where the analysis results vary as the mesh is refined due to localisation of discrete cracks . The strThe simulation results are compared to the experimental load–displacement relationships in For the concrete filled GFRP beam (S4), the FE model using tie constraint for interaction between concrete core and GFRP section predicted a maximum load of 460 kN which was significantly higher than the experimental result of 236 kN. This implied that the interaction at concrete–GFRP interface governed the failure load of the composite section. In this study, the interaction between GFRP webs and concrete was modelled using the surface to surface contact, a simplified modelling technique which ignored the initial concrete bonding. This contact algorithm allows normal separation of contact surfaces and shear transfer at the interface. However, the definition of the surface to surface contact resulted in the underestimation of the maximum load as the shear stress was mainly resisted by the concrete core causing concrete failed prematurely. It should be noted that GFRP webs acted as the reinforcement of concrete before bonding failure. In order to take into account the effects of reinforcement contributed by GFRP, the tensile strength of lightweight concrete was increased from 0.6 MPa (determined using Model code 2010 ) to 1.5 Using the validated FE model, three parameters further investigated were (i) thickness of web and flange, (ii) effectiveness of longitudinal stiffener on slender GFRP built-up section, and (iii) size of SHS at corners.Three thicknesses considered for web and C channel were 5 mm, 10 mm, and 20 mm. The predicted maximum load by varying the thickness of these components is shown in The effectiveness of GFRP longitudinal stiffener in restraining the web buckling of GFRP built-up closed section was investigated by reducing the web thickness to 2.5 mm. The web buckling could be observed for the hollow section, as shown in In this section, two geometry parameters investigated were the thickness and height of SHS. Two thicknesses studied were 5 mm and 6.3 mm. Two sizes of SHS considered for 5 mm thickness were 38 mm × 38 mm × 5 mm and 50 mm × 50 mm × 5 mm, while 25 mm × 25 mm × 6.3 mm and 75 mm × 75 mm × 6.3 mm were studied for 6.3 mm thickness. The maximum load for the GFRP built-up section using different SHS is illustrated in (a)The GFRP hollow built-up sections failed by web crushing at the supports due to orthotropic material properties of GFRP. The rotational stiffness at the web–flange junction governed the maximum load of the built-up beam, and increasing the thickness of the C channel could improve the maximum load more effectively than increasing the web thickness. The longitudinal C channel stiffener could prevent the web buckling of slender GFRP hollow built-up section, and the maximum load increased by 136% for the web thickness considered in the numerical study.(b)The built-up section with square hollow sections at corners demonstrated 47% load improvement due to the enhancement of stiffness at the web–flange junction. Increasing the height and thickness of SHS could improve the maximum load of the built-up section. The height of the SHS section showed a greater influence on the maximum load than the thickness of SHS.(c)Concrete infill improved the stiffness and maximum load by preventing web crushing failure of GFRP section. It achieved the highest maximum load increment of 162% among the parameters considered in this study. It was found that the maximum load was influenced by the bond–slip behaviour at the concrete–GFRP interface, and the failure was caused by the shear crack in the plain concrete core.In this study, the shear behaviour of GFRP hollow and concrete filled built-up beams was studied experimentally and numerically. The rectangular hollow built-up section was fabricated using two pultruded GFRP C channels, and two pultruded GFRP plates bonded using epoxy adhesive. The parameters considered including longitudinal web stiffener, strengthening at the web flange junction and lightweight concrete infill. Based on the experimental and simulation results, the following conclusions were drawn:Even though concrete infill is the most effective alternative for improving the stiffness and maximum load, the numerical simulation for shear behaviour of concrete filled GFRP composite beam is very challenging due to the bond–slip at the concrete–GFRP interface. More research is needed to study the interaction at concrete–GFRP interface subjected to shear and normal force, as it is the key information required to improve the capability of the FE model.