A cascade control structure for the simultaneous position and stiffness control of antagonistic tendon-driven variable stiffness actuators (VSAs) implemented in a laboratory setup is presented in the paper. Cascade control has the ability to accelerate, additionally stabilize, and reduce oscillations, which are all extremely important in systems such as a tendon-driven compliant actuators with elastic transmission. Inner-loop controllers are closed in terms of motor positions, and outer-loop controllers in terms of actuator position and estimated stiffness. The dominant dynamics of the system (position and stiffness), composed of the mechanical part and inner loops, are identified by a closed-loop auto-regressive with exogenous input (ARX) model. The outer-loop controllers are tuned on the basis of experimentally identified transfer functions of the system in several nominal operating points for different stiffness values. After the system is identified, a controller bank is generated in which a pair of actuator position and stiffness controllers correspond to a nominal operating point and covers the area surrounding the nominal point for which it is designed. The controllers used are integral-proportional differential (I-PD) and integral-proportional (I-P) controllers, which are a variation of the PID and PI controllers with dislocated proportional and derivative gains from a direct to feedback branch that result to no overshoot for even fast reference changes , which is essential for preventing tendon slackening (meeting the pulling constraint). Analytical formulas for controller tuning based on only one parameter, λ, are also presented. Since position and stiffness loops are decoupled, it is possible to change λ for both loops independently and adjust their performance separately according to the needs. Also, the controller structure secures the smooth response without overshooting step reference or step disturbance signal, which make practical implementation possible. After all the controllers were designed, the cascade control structure for simultaneous position and stiffness control was successfully evaluated in a laboratory setup. Thus, the presented control approach is simple to implement, but with a performance that ensures a pulling constraint for tendon-driven actuators as a foundation for bioinspired antagonistic VSAs. Robotics has made major strides in recent decades. They began with the deployment of the first industrial robots in a known environment without humans in their immediate proximity. These robots had standard stiff actuators, while elastic deformation in their transmission system was deemed undesirable. The undesirable elasticity could induce oscillations, which engineers attempted to eliminate as early as the mechanical system design stage  with constant actuator stiffness , copied from humans and animals and implemented in robots , which will be discussed below. The motivation also traces to earlier activities and papers of the authors in the areas of modeling  but using widely accepted model identification tools for actuator system modeling. Thus, the approach can easily be applied to other types of antagonistic VSAs since the exact VSA parameters are rarely manufactured to fully match its mechanical design due to the complexity of their structure. The paper proposes a control scheme and procedure for controller tuning of antagonistic VSAs that is easy to implement while keeping tendons under tension to prevent slacking. The identified transfer functions present locally linear behavior of the system; thus, controllers are tuned to satisfy stability criteria for linear systems with a certain amount of robustness. The control design is simplified to the selection of one parameter for trading-off between performances and robustness, which shapes all the parameters in the introduced control structure.In our approach, we presented a cascade control structure for position–stiffness control of antagonistic VSAs, where controller tuning is achieved based on an identified system dynamic. The cascade control structure gives better performance for reference tracking than the classical single-loop control system  and ESP+ control approaches  between the motor and the link needs to be non-linear, with a monotonously incremental force relative to extension :by combining Equations (10) to (12), Equation (13) for actuator torque follows:S is defined by Equation (14).Actuator's stiffness qe for the symmetrical system shown in The equilibrium position of the actuator The expression for actuator stiffness is derived by combining Equations (3) and (4) with Equations (13) to (15):In order to make the approach versatile and applicable to a different kind of antagonistic VSAs, several main actuator characteristics have to be estimated. Initially, each individual drives and gearing have to be identified as a core of the internal loop. Elastic transmission elements determine the actuator dynamics, and consequently, they have to be well-estimated for the control purposes as well as for the evaluation of the actuator performances. Finally, for the sake of reliable and robust position and stiffness control, outer loops that comprise inner loops, elastic transmission, and actuator mechanical design have to be identified.Gm(s) were identified. The transfer function was assumed to be a second-order transfer function without time delay, where voltage is the input and motor position the output. The parameters were estimated by first estimating those of the motor speed transfer function, without payload, described as a first-order transfer function without time delay, which is a common approximation in engineering. In general, velocity/voltage transfer function of the motor gearbox set is a second-order transfer function with two real poles on the left side of the complex plane, where one pole is determined by electric characteristics and the second pole is determined by mechanical characteristics. The mechanical component of the system is significantly slower than electrical; thus, its dynamic behavior is dominant and transfer function can be estimated as a first-order transfer function  with estimated parameters is:Fast system dynamics is determined by the electric drive and its gearbox. The goal of the control approach is to accurately and promptly control antagonistic drive positions so the outer position and control loops are preserved. In order to tune the inner loop, the parameters of the assumed geared motor transfer function Km = 2.86 is the estimated gain factor and Tm = 0.22 is the estimated time constant.where k0 = −2.498 N, k1 = 331.49N/m, and Actuator dynamics and its stiffness are determined by elastic elements used in the transmission. In order to estimate actuator stiffness according to (16), spring parameters need to be estimated as well. If actuator elastic elements/springs are changed, spring parameters must be estimated again. To accurately determine the spring coefficients, the spring characteristic was captured by measuring forces and spring elongations at different loads. The fits of the spring function for 2nd-, 3rd-, and 5th-order polynomial satisfying the least square error are shown on the top plot, while estimation errors are shown on the bottom plot in Finally, actuator performances depend on its electromechanical design as a whole. Gq(s)] and stiffness [GS(s)]. The control loop for identification consists of controller Cp(s) and transfer function Gp(s) that include both actuator position and stiffness transfer function: Gq(s) and GS(s). Transfer function Gp(s) includes the mechanical design of the antagonistic actuator with elastic transmission elements and inner loops as shown in Cp(s) controls the tendon tension force in the outer loop around a nominal point. For identification purposes, controller Cp(s) in the outer loop does not need to be optimally tuned but stable. In general, the feedback need not to be same as the output variable, which is being identified, it only needs to be stable in order to avoid output drift and keep the system around a nominal setpoint. Also, closed-loop identification is carried out to reduce the influence of sensor noise and therefore improve identification. Based on the inputs and the outputs of the system Gp(s), dominant dynamics of the actuator position and stiffness is identified.A and θB, and two outputs: actuator position and stiffness q and S. Given that the system is symmetrical and that both inputs contribute equally to the output, identification is undertaken with respect to only one motor, while the other is kept still. Without loss of generality, it is deemed that θB = 0.The system shown in Since the system is non-linear, it was identified in the vicinity of several operating points, for tension forces of 10, 20, 30, and 40 N, which correspond to the estimated stiffnesses of 8.24, 10.55, 12.43, and 14.06 Nm/rad, respectively. The stiffness range is limited by the properties of the actuator design and compression springs, which are fully compressed at 50 N. However, the proposed control approach is invariant to the stiffness range.While the outer loop keeps the system at a nominal tension force, a low-amplitude PRBS (pseudorandom binary sequence) signal is added to the input-desired motor position, just enough for its effect to be visible at the output and distinguishable from sensor noise  (motor A reference position of Arefθ) and output , the ARX model was used to identify the dominant dynamics for actuator position and stiffness at each of the nominal values. The dominant dynamics is the lowest-order polynomial transfer function whose response adequately mimics the real response of the system. Gq(s) and stiffness GS(s) of the antagonistic actuator at various nominal points obtained through identification, where Gq(s) and GS(s) are grouped in Gp(s) from Based on the measured input of the system Results are divided into two groups: first- and third-order estimations of the transfer function. All estimated function of the third order has one real pole and one pair of conjugated complex poles. A pair of conjugated complex poles produces some oscillatory dynamics, but the real pole is at much lower frequencies; thus, this dynamics is dominant and system transfer function can be approximated as the first-order transfer function. The predominance over the oscillatory dynamics could be explained by the existence of the inner loop controller, which shapes on overall input/output dynamics.The control structure is realized as a cascade control structure for simultaneous position and stiffness control, which is shown in The cascade control structure shown in All controllers used in the inner and outer loops are integral-proportional differential (I-PD) or integral-proportional (I-P) controllers, with a filter   and second-order polynomial for stiffness (16) of the actuator in the state of equilibrium.Static decoupler D  reproducEquations (17) and (18) can be written in matrix form as:D is the system decoupler and where matrix In cases when stiffness is presented as higher-order polynomic or a complex non-linear equation  is the controller that regulates the operation of the motor. The actuator range used in the experiments is 180 deg, which corresponds to 10 times wider motor range according to joint/motor pulley radius [see Equation (15)]. Another constraint in the experiments is the stiffness range (8–15 Nm/rad). The constraints are caused by the mechanical design of the actuator. Maximal disturbance introduced as an additional spring tension in robustness testing is 50 N, which corresponds to 0.375 Nm torque disturbance at the gearbox shaft. The value msm = 1.4 was determined experimentally; in such a way that it is a good trade-off between trajectory tracking performance and robustness. The desired value of msm for motor transfer function identification is achieved at λ = 0.0854. The controller parameter kr can be tuned in the (0 − kp) range, and the value of parameter b is in the (0–1) range. If b is higher, when the reference changes, the system will respond more quickly but the overshoot will also be larger. Without loss of performance in terms of disturbance rejection and robustness, b = 0 and, hence, kr = 0 is selected. Rejection of the overshoot is an essential requirement in the inner loop, which should prevent oscillation in compliant tendon-driven actuation. Since the system is symmetrical, both motors have the same controllers.The controller was designed to satisfy the desired sensitivity function K and time constant T.This section introduces guidelines for tuning of the outer control loops–actuator position and stiffness control. For transfer functions of the first and third orders for position and stiffness given in b = 0 were adopted for all position and stiffness controllers and present initial tuning.Given that the transfer functions were identified as first-order transfer functions without time delay, the outer loop controllers were tuned like I-P controllers according to Boskovic et al. . The I-Pkp; ki, and kr need to be divided by the gains introduced by the decoupler. According to the decoupler values from (20), actuator position gains should be divided by Given that the decoupler introduces a gain between the outer loop controller output and the reference positions of the motor, in order to retain the performance of the designed controllers, gains S1 to S2, controller 2 from S2 to S3, controller 3 from S3 to S4, and so on. In this research, bumpless switching between controllers is used . Another application is to use a certain type of gain scheduling, where controller gains are computed as a linear combination of the two nearest controllers, depending on the nominal for which they were designed and on the desired value.In the case of non-linear systems, due to different dynamics in different operating points, controllers can be designed for a linearized model, for each of the operating points of a set, thus forming a controller bank or set. The set of controllers can be used to control the system in such a way that each of the controllers would be tasked with a part of the operating range, for example, controller 1 would cover stiffness from It is of most importance to ensure a pulling constraint and avoid tendon slacking. Therefore, outer loops could be easily prioritized to ensure pulling constraint by making position control slower than stiffness control, which guarantees no slacking and, thus, allows validation on the laboratory setup. This can be achieved by adjusting the parameter λ separately for each of the outer loops, since the response time is proportional to the parameter λ for each loop individually . In the second experiment, actuator stiffness/compliance control is validated by tendon force measurements, and therefore, stiffness is estimated directly from actuator torque and position measurement (12).S = 10.55 Nm/rad. First, the position reference was specified as a step signal sequence in the range from –π/3 to π/3, while stiffness remained at 10 Nm/rad, and then, the position was held constant while stiffness was varied as a pulse signal in the range from 8 to 14 Nm/rad. D. Therefore, outer position loop is not aware of the externally applied torque. Trajectory tracking performance will depend on the accuracy of the motor and actuator radii as geometric actuator parameters, which are easy to measure. The torque that acts on the link in the state of equilibrium is equal to 0, such that disturbance Fext, which is a manually entered force that acts tangentially on the actuator link, was measured as the difference between the forces that act on the actuator, measured in the stationary state:In the second experiment, actuator stiffness tracking is evaluated by measuring tendon forces and actuator position. To test the stiffness, the reference actuator position was set at 0 and the reference stiffness at 10 Nm/rad. In this case, only the stiffness controller is used in the outer loop to achieve compliant behavior. The actuator position control is in the open loop, where regulation relies on the geometrical relation (14) implemented through the static decoupler Instead of a derivative (12), can be represented by means of a linear approximation, as the quotient of the torque change and angle change:rj, so actuator stiffness will be estimated from the applied force, which could be directly measured by sensors. Since the nominal angle is 0, and the torque acting on the actuator is rj (FA − FB),Note that externally applied torque is related to externally applied force by a scale factor qm is the instantly measured actuator position . Therefore, the externally applied force could be estimated based on measured actuator position and commanded stiffness as follows:holds for (21), where rj is constant and that the stiffness is held constant, the correlation between the force and the position change is also constant. q. The external force Fext, which is the difference between measured forces FA and FB, and the expected force Fexpected based on (23) for the measured position and commanded stiffness are depicted on Given that the actuator radius Looking toward future robot actuators that comprise intrinsic compliance for safety and energy efficiency, tendon-driven actuation for reducing robot inertia, and antagonistic configuration with non-linear transmission for enabling bidirectional moves and variable actuator stiffness/compliance, this paper elaborates design and control of tendon-driven compliant antagonistic VSA that can be applied on all antagonistic VSAs. Since the antagonistic design of VSA, mastered by nature through evolution, presents a foundation for moving of humans and mammals in general, this is undoubtedly a design of future robot actuators, which aims to work in the human-centered environment. This research introduces a conventional engineering control approach based on cascading structure to a bioinspired compliant antagonistic actuator.A cascade structure for simultaneous position and stiffness control of an antagonistic VSA was presented and experimentally tested in the paper. A cascade structure contributed to the stability of the system because a proper inner-loop controller design reduced oscillations at the output from the system, which can occur especially in mechanical systems that feature elastic transmission. Robust controllers were designed for motor positions on the basis of experimental identification of the gearbox motor transfer function. In addition, locally linearized actuator position and stiffness transfer functions were identified with motor position inner-closed loops, such that the controller dynamic was included in the identification. The linear system control theory for controller tuning was applied. A static decoupler was designed based on an estimated spring model and a mechanical design of the actuator.The advantage of this approach involving system identification is that it requires no previous knowledge about the model of the system and no information about system parameters, such as motor and actuator friction and inertia, gearbox efficiency, force sensor mass, etc. Another advantage is that it is not necessary to measure or control motor torques. Control is achieved via voltage, and the connection between voltage and torque is included in the dynamic that is being identified. Only a part of the system model is required, related to actuator stiffness and position (13) and (14), as well as (15), whose relations were determined experimentally. Consequently, a similar control system design principle can be applied to different types of antagonistic VSAs.The structure of the I-PD/I-P controllers that were used is selected to satisfy pulling constraint of tendon-driven actuators. The controllers were designed with the desired robustness, such that apart from the dynamics disregarded in the identification process due to their minor effect, and in the case of non-modeled dynamics occurring during continuous operation of the system due to a change in any of the system parameters, the controllers will maintain stability and good trajectory tracking performance. The main feature of the applied controllers is the easy tuning of the system performances as a trade-off between robustness and speed/performance, by changing only one parameter—λ. Therefore, by changing λ online, the great flexibility for the system adaptation to different scenarios and change of the robustness/performances for different operating points are feasibly and easy. The robustness is of great importance in tendon-driven compliant systems so the pulling constraint is successfully tackled.In order to control antagonistic VSAs more appropriately, especially when a broader stiffness range is available, the controller bank is used. Each controller in the bank is tasked with covering a span around the nominal point for which it was designed, while bumpless switching between controllers is exploited.Performances of controllers are verified in two experiments: simultaneous position and stiffness tracking while their references are changing separately while actuator stiffness is estimated from the model, and actuator stiffness/compliance control validated by stiffness calculated from force measurements directly.Extending this control structure to the other types of VSAs requires modification of the current approach. In general, a VSA is a two-input–two-output system. If the actuator stiffness and position are not coupled, the actuator can be observed as two single-input–single-output systems that can be adjusted independently. In a more complex case, if the actuator stiffness and position are coupled, a modification of the proposed approach is needed. The first difference to the presented approach is the identification procedure since input/output dynamic behavior is not symmetric, as it is the case of the antagonistic structure. The same cascade control structure can be kept, but the identification must be conducted from both input channels. To enable the generalization approach presented in this paper to the wider class of the VSAs, it is necessary to overcome the problem of the asymmetric input–output transfer function of VSAs. This can be achieved by introducing the dynamic decoupler that will make outer loop control decoupled from the system. Dynamic decoupler is computed based on locally identified transfer functions (Nordfeldt and Hägglund, Further research will examine additional system identification methods, which could lead to more flexible actuator identification procedures and therefore facilitate the broader use of the presented approach to a wider class of VSAs. Also, the influence of different non-linear transmission elements will be evaluated. To increase robustness of the actuator, different approaches to disturbance rejection would be considered (Guo et al., The datasets generated for this study are available on request to the corresponding author.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


Purple sweet potato starch is a potential resource for resistant starch production. The effects of heat-moisture treatment (HMT) and enzyme debranching combined heat-moisture treatment (EHMT) on the morphological, crystallinity and thermal properties of PSP starches were investigated. The results indicated that, after HMT or EHMT treatments, native starch granules with smooth surface was destroyed to form a more compact, irregular and sheet-like structure. The crystalline pattern was transformed from C-type to B-type with decreasing relative crystallinity. Due to stronger crystallites formed in modified starches, the swelling power and solubility of HMT and EHMT starch were decreased, while the transition temperatures and gelatinization enthalpy were significantly increased. In addition, HMT and EHMT exhibited greater effects on the proliferation of bifidobacteria compared with either glucose or high amylose maize starch. Ipomoea batatas L.) originated from Latin America, and is now cultivated worldwide, especially in Africa and Asia. China accounts for most of worldwide sweet potato production. The skin and flesh colors of sweet potato vary from white to yellow-orange and deep purple. Purple sweet potatoes contain a significant content of anthocyanins [Sweet potato  , enzyme Although the physicochemical characteristics of native and resistant starches from sweet potato have been extensively studied ,14,15, aIn the present study, resistant purple sweet potato starches were produced by HMT and enzyme debranching combined heat-moisture treatment (EHMT). The physicochemical and crystallinity properties of native, HMT and EHMT starches from purple sweet potato were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier Transform infrared (FT-IR) spectroscopy. In addition, the effects of these starches on the proliferation of bifidobacteria were assessed and compared with those of glucose (GLU) and high amylose maize starch (HAMS). The physicochemical properties of resistant starches from purple sweet potato prepared by HMT and EHMT were assessed in order to evidence the potential use as probiotics.The chemical compositions of native, HMT and EHMT starches are shown in The shapes and surface characteristics of native, HMT and EHMT starches prepared from purple sweet potatoes are shown in When starch is heated in water above its gelatinization temperature, the resulting irreversible changes result in loss of crystallinity, granule swelling and leakage of carbohydrate material . VariatiCompared to the swelling power of native starch 26.21 g/g), the swelling power of HMT starch decreased to 20.72 g/g, while EHMT starch exhibited the lowest swelling power of 17.21 g/g. During HMT, the internal of starch granules was rearranged, and the mobility of the molecules would be increased, and thus cause enhanced associations between interacting amylose-amylose and amylose-amylopectin chains. The resulting rigid structure could restrict the swelling of starch granules. This result was consistent with previous reports, where the swelling power was reduced during HMT of rice starch  and sorg g/g, theThe solubility of native starch determined at 90 °C was 9.46%, which was relatively low compared to the sweet potato starches (8.56% to 19.97%) . This mioT, pT and cT), the gelatinization temperature range (cT–oT) and gelatinization enthalpy (ΔH) of native, HMT and EHMT starch samples are presented in The gelatinization transition temperatures (oT and least for cT) and decrease the gelatinization temperature range, which is consistent to other starches [Compared to the native starch, HMT has been shown to increase the gelatinization temperatures  represents an overall measure of crystallinity  and is closely related to the loss of molecular order within the granule. Furthermore, the starch samples with higher RS content, which contributes to the increase of the perfection of double helical order and formation of stronger matrix or network, had a higher ΔH value. Therefore, as presented in H value.Gelatinization enthalpy , those of HMT and EHMT starches (33.72% and 35.68%) were both decreased, which was due to the damage of the crystalline region and partial gelatinization of the starch granules during HMT. The enzyme debranching combined HMT caused a higher crystallinity than HMT alone, which could be explained by the higher RS content after debranching [6.14%, thInfrared spectroscopy provides information about bonds whose dipole moment changes during vibration, which enables analysis of the short-order range such as chain conformation and double helical order of starch granules. The changes in peak intensity indicate characteristics of the conformational change in the starch.−1 was assigned to hydroxyl group stretching vibrations, and the broad band was due to the complex vibration stretches of intermolecular hydroxyl groups; the peak at around 2930 and 1640 cm−1 were associated to −CH2 stretching vibrations and deformation vibrations of the hydroxyl groups in water, respectively. The weak bands at 1370 and 1420 cm−1 were attributed to the twisting and bending shake of −CH2.−1 reflects C-C, C-O, C-H stretching vibration and COH bending modes [−1 and 1083 cm−1 are associated to the ordered structures of starch, while the band at 991 cm−1 is associated to the amorphous structures of starch [−1) [−1) in native, HMT and EHMT starches were 0.725, 0.755 and 0.759. The greater R values of HMT and EHMT would indicate the higher levels of order in the external regions of the starch granule.The absorption region from 800 to 1200 cmng modes , changesng modes . The banf starch . The amorch [−1) . The rat600 nm value) increased with the higher concentration of the different carbon sources, and reached the highest level at the concentration of 20 g/L. The GLU group reached the highest level at the concentration of 15 g/L.To evaluate the potential probiotic effects of HMT and EHMT starch from purple sweet potato, different carbon sources including glucose , high amylose maize starch , HMT starch and EHMT starch were applied to the media of bifidobacteria culture. At a carbon source concentration of 40 g/L, the number of bifidobacteria decreased in all the tested media. These data might be attributed to a high osmotic pressure induced by high concentrations of carbon sources . Compare600 nm values of media containing HAMS, HMT or EHMT starch were significantly higher than that of media containing GLU during cultivation, while EHMT starch exhibited an obviously higher value than HAMS and HMT starch. In the medium, the increase of bifidobacteria accompanied a reduction in pH during fermentation, which is due to the accumulated metabolites. As shown in To further assess the probiotic effects, the growth curves of bifidobacteria and the variation trend of pH values of media during cultivation were plotted during cultivation. Based on the previous result , the carThe purple sweet potato Xinyin No.1, a popular cultivar in south China, was freshly harvested, and the tubers were washed, peeled and cut into small pieces, and then blended with three times as much water (by weight) in a domestic blender for 3–4 min. The resulting slurry was passed through fine gauze to separate the cell debris and the suspension was blended with water and filtered three more times to wash the starch into the filtrate, and allowed to settle overnight at room temperature. The precipitated fraction was collected and dried in a DJG-9053A oven  at 45 °C for 24 h, and then ground using a FW135 grinder , and filtered using 100-mesh sieve to obtain the purple sweet potato starch . The resPurple sweet potato starch  was mixed with distilled water (250 mL), and moisture content was adjusted to 35%. The starch slurry was pre-gelatinized in a boiling water bath (110 °C for 40 min). The sample was cooled to room temperature and stored at 4 °C overnight in a refrigerator. Successively, the sample was dried at 60 °C for 16 h and milled to pass a 100-mesh sieve for further analyses.w/v) was gelatinized with distilled water by stirring. The starch slurry was pre-gelatinized in a boiling water bath, and then cooled to 60 °C, and debranched by pullulanase  at the concentration of 25 ASPU/g with a pH of 4.8 [Purple sweet potato starch  with the description of Association of Official Analytical Chemists (AOAC) 2002.02.The dried starch samples were coated with a thin film of gold (10 nm) in vacuum situations and the morphology of starch samples were observed under a scanning electron microscopy .Moisture, lipid, and protein contents of starch samples were determined according to the methods described by Miao and co-workers . Total ag for 20 min, the supernatant was placed in an oven at 105 °C for 4 h to obtain the weight of dissolved starch, and the sediment of the centrifugation was also weighted. The solubility  and swelling power  was calculated as follows:Water solubility and swelling power were determined on the basis of the method described by a previous report with slight modifications .The starThermal properties were analyzed using an F3 200 Maria Differential Scanning Calorimeter  according to the reported method with slight modifications . A starcThe starch samples were submitted to an X-ray diffractometer  operating at 40 KV and 30 mA at diffraction angle 2θ of 5° to 45° at speed of 2°/min. The graphs were analyzed by PeakFit 4.12, and then the relative crystallinity was calculated.−1 was used for scanning at a resolution of 4 cm−1 for 32 scans.The IR spectrum of starch was recorded on a Nicolet Avatar 360 FR-IR spectrometer  at room temperature. The starch sample (2 mg) was blended with KBr powder (150 mg) by grinding for 10 min under the infrared lamp, and pressed into tablets before measurement. A region from 400 to 4000 cmTo investigate and compare the prebiotic effects, four types of carbohydrates were used as carbon source in the mediums. The fermentation mediums containing glucose , HMT, EHMT, or HAMS  were prepared with the various carbon source concentration of 5, 10, 15, 20 or 40 g/L. The resulting fermentation mediums were sterilized at 115 °C for 20 min.v/v) was transferred to 15 mL of fermentation medium. The incubation of bifidobacteria was performed in an anaerobic incubator  at 37 °C. The proliferation rate of bifidobacteria was determined by plotting the OD600 nm and pH values of the fermentation mediums at 0, 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 h, respectively [To get an inoculum, bifidobacteria  were incubated for 48 h in 15 mL of fermentation medium with glucose in anaerobic bags . The resulting inoculum  or Peakfit 4.12 software . Statistical significance was set to Native PSP starch is a cheap and abundant starch containing relatively high amylose content, which makes it a potential resource for RS production. After heat-moisture treatment (HMT) or enzyme debranching combined heat-moisture treatment (EHMT), the morphological, crystallinity and thermal properties of PSP starches were significantly modified. The native starch granules structure was destroyed to form a more compact, irregular and sheet-like structure. The crystalline pattern was transformed from C-type to B-type with decreasing relative crystallinity. The swelling power and solubility of HMT and EHMT starch were decreased, due to the enhanced interactions between amylose-amylose and amylose-amylopectin chains. Stronger crystallites were formed in modified starches, and thus the transition temperatures and gelatinization enthalpy were significantly increased. These gelatinization properties indicate that HMT and EHMT starches could be stable during high temperature processing. In addition, HMT and EHMT exhibited greater effects on the proliferation of bifidobacteria compared with growth in the presence of HAMS, indicating the great potentiality of using them as probiotics in food industry.


Ten years ago, the directors of The Company of Biologists, all practising scientists, made the decision to launch a new journal aimed at researchers who investigate human disease using model organisms . They beBiomedical research journals such as DMM sit in an ecosystem that is subject to alterations from various sources – technological, financial and policy, in addition to advances in the science itself. The academic editors of DMM, currently led by Editor-in-Chief Monica Justice and Senior Editor Ross Cagan, work closely with the editorial team in Cambridge, UK, to ensure that DMM serves its community of readers, authors and reviewers as effectively as possible within this ecosystem .As the journal marked its first decade, it was agreed that the long-term editorial succession and journal strategy should be reviewed. Because DMM strives to be a journal that serves its community, it was therefore obvious that any decision about the future of DMM must involve discussion with its authors, reviewers and readers. A plan was initiated for a community consultation regarding the future direction of DMM.This consultation will be steered by a subgroup of Company directors: Peter Rigby, Daniel St Johnston and Paresh Vyas. As you will see, the consultation includes gathering suggestions for a future Editor-in-Chief. This should be someone who will maintain DMM's high standards for model organism work, while promoting new fields, to ensure that the journal is forward-looking and reflects the directions of the DMM field. It should be someone who has a medical disease focus, and whose work bridges the gap between basic research and clinical science (from bench to bedside). They might perhaps be someone who has shown commitment to DMM  over a period of time.dmm.feedback@biologists.com or get in touch with any of us individually.What are the strengths of DMM?What weaknesses does DMM have?What niche does DMM currently occupy?Into which (new or existing) areas would you like to see DMM expand in the future?Is DMM seen as a community journal?http://dmm.biologists.org/content/about#COMMUNITY.)What else could DMM do to support our field? (See Your suggestions for new Editor-in-Chief (with brief reasons please).As well as the key matter of the Editor-in-Chief role, we also want to consult the community about the strengths and weaknesses of DMM, where we can improve, which (new or existing) areas the journal should expand into and what more we can do to support our field see . We welcAlthough a mere stripling compared with our more venerable sister journals , the ten years since journal launch have seen substantial change. DMM was launched as a print and online subscription journal, at a challenging time for library budgets and when the campaign for improved access to research was flourishing. The directors of The Company of Biologists made the decision to move to an author-pays Open Access model and to support DMM through what could have been a difficult transition . HappilyAs well as the day-to-day decisions made concerning submissions to the journal, the team thinks more strategically; for example, deciding which areas to devote to special issues of DMM and evaluating the current scope of the journal to ensure that it keeps pace with the science. They make decisions about the operation of the journal, such as the recent move from issue-based article publication to continuous publication, and offering format-free submission. In an Editorial published in February 2018 , we promDMM has kept an eye on discussions about the role of preprints in science communication and has long had preprint-friendly policies, including the two-way integration of its submission system with bioRxiv. DMM readers  have been beneficiaries of the launch of preLights – the new preprint highlights service run by the biological community and supported by The Company of Biologists. A team of scientists, several of whom were recommended by DMM Editors and Editorial Board members, regularly review, highlight and comment on preprints they feel are of interest to DMM. You will now find preprint highlights relevant to DMM on our tables of contents; do let us know if you are finding this useful. We await the launch of MedArXiv with curiosity, especially given the debate within the medical community about possible risks arising from posting non-peer-reviewed clinical research.DMM is extremely lucky to have both Monica Justice and Ross Cagan as its senior leadership; both will remain in place while we gather and review the feedback over the coming months. It is vastly more important to do this right than do it quickly, to ensure that DMM continues to publish research that enhances our understanding of disease mechanisms and the development of novel diagnostics and therapeutics.


This study reviewed the use of a combination of meshed dermis graft and cultured epithelial autografts (CEA) made in Japan “JACE”  for the treatment of massively burns. JACE is a Green-type CEA. We recently described a method in which we prepare the wound bed for burned patients by using artificial dermis and graft with JACE on a meshed 6:1 split-thickness autograft. In this report, we used a meshed 3:1 split-thickness dermis graft without epithelial cells. There are several reports of combination of using CEA on meshed split-thickness autograft, however this is the first report of using CEA on meshed split-thickness dermis graft.Between March 2015 and August 2017, 3 burn patients were enrolled in this study. The patients ranged in age from 51 to 66 years. All 3 patients suffered severe burn injury that caused by flame. % Total Body Surface Area (TBSA) burned were ranged from 37.5% to 69%.All patients received surgical treatment with tangential excision within a week from admission. We implanted artificial dermis immediately after debridement. Basically, we applied meshed 6:1 split-thickness autografts to the wound bed and covered with JACE. However, in the absence of split-thickness autografts, we used a meshed 3:1 split-thickness dermis graft instead of a meshed 6:1 split-thickness autograft.At 3 weeks after the transplantation of JACE, the take rate for JACE sheets was >60% on the meshed 3:1 split-thickness dermis graft. Furthermore, almost all of the burn wounds had healed at 6 weeks after surgery.We observed good results by grafting JACE on meshed 3:1 dermis graft. With this new method, it is possible to cover a large burn wound by harvesting tissue from only a small site. Since 1984, when good results were achieved in extensively burned children through the use of CEA, the usefulness of Green-type CEA has become widely recognized.–5 CEA made in Japan “JACE”  is a Green-type CEA that was developed in Japan. Since 2009, JACE has often been used for >30% Total Body Surface Area (TBSA) burn patients.Severely burned patients can require many clinical treatments including burn resuscitation, respiratory support, nutritional support, infection control, pain management, dressing and surgery. Advances in medical treatments have helped to improve survival rates. We obtained good results and observed the engraftment process by both transmission electron microscopy and scanning electron microscopy. We reported that the dermis from the autograft extended underneath JACE, and there was binding between JACE and the dermis.In a previous report, we prepared the wound bed for burned patients by using artificial dermis and graft with JACE on a meshed 6:1 split-thickness autograft.In the present study, we treated 3 massively burned patients. We used JACE on a meshed 3:1 split-thickness dermis graft instead of a meshed 6:1 split-thickness autograft for part of the burn wound. We achieved good results in all 3 cases.This report describes the use of a combination of meshed dermis graft and JACE for the treatment of massively burned patients. There are several reports of the combination of using CEA on meshed split-thickness autograft; however, this is the first report of using CEA on meshed split-thickness dermis graft.2Burn patients who were treated with a combination of meshed dermis graft and CEA were reviewed. Between March 2015 and August 2017, 3 burn patients were enrolled in this study, which was approved by the institutional review board  after we obtained consent from the patients’ families. We harvested full-thickness normal skin from unburned areas within 48 hours. We were able to use JACE 3 weeks after this harvest.,9All patients received surgical treatment with tangential excision within a week from admission, and all necrotic tissue was removed. We implanted artificial dermis immediately after debridement. A week later, we began to apply dressings using Vaseline petroleum jelly and Trafermin  every day to construct a wound bed. In the immediate postoperative period, the grafted areas were left exposed to air for 4 hours each day to allow the JACE grafts to dry. Takedown  generally occurred 1 week after placement of the grafts. Dressings were applied with Vaseline petroleum jelly after takedown. Almost all of the wounds closed within 4 to 6 weeks.Basically, we applied meshed 6:1 split-thickness autografts to the recipient wound bed and covered with JACE. However, in the absence of split-thickness autografts, because of extensive burn and lack of intact skin area, we used meshed 3:1 split-thickness dermis graft instead of meshed 6:1 split-thickness autograft. After implanting JACE, we followed Sood protocol for cultured epithelial autograft dressings.33.1A 69-year-old Asian male was suffered severe burn injury that caused by flame. The patient had no known comorbidity but had drunk much alcohol every day. The patient has second to third-degree burns on face, chest, abdomen, both arms, and both buttocks that affected 37.5% TBSA. Second-degree burn was estimated 9.5% TBSA and third-degree burn was estimated 28% so that Burn Index was 32.75. Upon admission and after cleaning the fresh burn and removing blisters, we changed dressing every day. We harvested full-thickness normal skin from right groin area in order to manufacture JACE on next day. We performed debridement all eschar on 7 days from admission. And we implanted artificial dermis on the all ulcer to manage the good wound bed. At last, we applied JACE on meshed 3:1 split-thickness dermis graft or meshed 6:1 split-thickness autograft for covering all wound. All skin graft take rate was 90% at four post-operative weeks. And this patient was transferred to a rehabilitation hospital on 101 days from admission.3.2A 51-year-old Asian male was suffered severe burn injury with inhalation injury that caused by flame. The patient had no known comorbidity. The patient has second to third-degree burns on face, chest, abdomen, right side of the back, both arms, right thigh and left lower leg that affected 44.0% TBSA. Second-degree burn was estimated 34% TBSA and third-degree burn was estimated 10% so that Burn Index was 27. We harvested full-thickness normal skin from right groin area in order to manufacture JACE on 2 days from admission. And we performed debridement all eschar and we implanted artificial dermis on the all ulcer on the same day. We implanted meshed split thickness skin graft on back in advance on 17 days from admission. This is because the patient will need absolute rest after using JACE and generally CEA take rate on back is very low. We finally applied JACE on meshed 3:1 split-thickness dermis graft or meshed 6:1 split-thickness autograft on chest and abdomen and implanted only meshed 3:1 split-thickness autograft for upper and lower limbs wound on 24 days from admission. All skin graft take rate was 95% at four post-operative weeks. And this patient was transferred to a rehabilitation hospital on 77 days from admission.3.3A 55-year-old Asian male was suffered severe burn injury with inhalation injury that caused by flame. The patient had no known comorbidity. The patient has second to third-degree burns on face, chest, abdomen, back, both upper and lower limbs that affected 69.0% TBSA. Second-degree burn was estimated 48% TBSA and third-degree burn was estimated 21% so that Burn Index was 45. Upon admission and after cleaning the fresh burn and removing blisters, an escharotomy was performed. We harvested full-thickness normal skin from right groin area in order to manufacture JACE on the next day from admission. And we performed debridement all eschar and we implanted artificial dermis on the all ulcer on 6 days from admission. We applied JACE on meshed 3:1 split-thickness dermis graft on both upper limb and chest and implanted only meshed 3:1 split-thickness autograft for the rest wound on 27 days from admission. All skin graft take rate was 85% at four post-operative weeks. And this patient was transferred to a rehabilitation hospital on 86 days from admission.4 In 1975, Rheinwald and Green described the technique of cultivating autologous keratinocytes for autografting. The CEA was used clinically for the first time in the early 1980s. Since a report described that extensively burned children recovered by using CEA in 1984, the usefulness of Green-typed CEA became known widely.–5 Epicel  has been commercialized in United States as the first tissue engineering product in the world since 1988. After 20 years, JACE was developed and was also a Green-type autologous cultured epidermis. However, this was not a late-coming article of EPICEL because the process of manufacture was different.In 1963, Todaro and Green found 3T3 cells from mouse embryo cells. In such cases, collagen is poorly constructed, and the combination of JACE and meshed split-thickness autograft has a better take rate than JACE alone. A 6-year surveillance of the use of JACE in Japan found that the average take rate for graft sites treated with a combination of JACE and meshed autograft was 77 ± 29%.In Japan, the wound bed is often prepared using artificial dermis due to the scarcity of cryopreserved cadaver allograft. In this previous report, we undertook skin biopsies after transplantation of JACE and observed the engraftment process of JACE. We implanted JACE on meshed 6:1 split thickness autografts and we focused on the boundary of the autograft and JACE. In the scanning electron microscope, it was observed that papillary dermis migrated toward the central portion. And this dermis strongly bound JACE. If dermis can extend, we thought that only dermis would engraft. We implanted JACE on a meshed dermis graft and obtained good results.The reason for the better engraftment rate is that dermis extends and connects from the autograft and fills the mesh and strongly binds JACE.In this report, three patients were treated with a combination of meshed dermis graft and CEA. The follow-up period was 7 months to 3 years, with a mean of 1.9 years. All three patients were tolerated the procedure well without any complications. We present a case of No 2. Figure We obtained skin biopsy samples at three and 6 weeks after surgery and observed both by transmission electron microscopy Figs.  and 4. WWith this method, we can harvest multiple times at the same site, and can use JACE on meshed autograft and meshed dermis graft for burn wounds. A meshed dermis graft requires a longer healing period than a meshed split-thickness autograft, and thus, depending on the specific wound, a meshed dermis graft may not be the optimal choice. However, with this method, we can cover a large burn wound by harvesting from only a small site.This new method may change the strategy for treating massively burned patients.5All content and procedures described within conform to the principles outlined in the Declaration of Helsinki. All patients or their families provided their written informed consent to participate. The institutional ethics committee approved the study protocol.The authors thank Dr Hideyuki Muramatsu for technical advices with the treatments. And we also thank all the medical staff for the work and enthusiasm.Validation: Kotaro Yoshitake, Ryohei Tokunaka, Yuki Yoshida, Mikiko Oshima, Sayo Tatsuta, Taishi Hamada, Ayako Kamitomo, Akito Hamajima.Writing – original draft: Minoru Hayashi.


Just a day earlier, on 30 December, ProMED-mail published a post calling for more information about ‘A cluster of undiagnosed pneumonia - China (Hubei)’. The post indicated that there had been some 20 patients diagnosed with ‘atypical pneumonia’ with seven of them being severely ill [https://www.gisaid.org/).The situation has continued to evolve rapidly since then and just a few weeks later, as at 23 January, 614 laboratory-confirmed cases and 17 deaths have been reported [While more cases are being reported on a daily basis and there is evidence for some human-to-human transmission in China, a number of important questions remain unanswered. For example, there is no certainty about the source of the outbreak, the transmissibility of the virus as well as the clinical picture and severity of the disease.Eurosurveillance, we are publishing two articles on different aspects of the newly emerged 2019-nCoV. One is a research article by Corman et al. on the development of a diagnostic methodology based on RT-PCR of the E and RdRp genes, without the need for virus material; the assays were validated in five international laboratories [In this issue of ratories . Before ratories  to supporatories . It alsoToday, the WHO Director-General Tedros Adhanom Ghebreyesus, taking into consideration the deliberations of the members of the International Health Regulations (IHR) Emergency Committee on 2019-nCoV in their second meeting, decided not to declare a public health emergency of international concern.https://www.ecdc.europa.eu/en/novel-coronavirus-china.International health organisations such as the European Centre for Disease Prevention and Control (ECDC) and the WHO are monitoring the situation and provide regular updates. ECDC has set up a dedicated webpage on which updates and risk assessments with focus on Europe are available:


The following information is missing from the Competing Interests statement: WHO-IARC: Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.Norwegian Immunization Registry SYSVAK  provided data, but is not responsible for the analyses and interpretation in this article.The publisher apologizes for the error.


P = 0.001). When postoperative weight change was used as a continuous variable, the aHR for each 1% increase in postoperative weight was 1.045 . In addition, the ≥3% group was associated with EAD  and overall mortality . In conclusion, postoperative weight gain may be independently associated with increased risk of graft failure, EAD, and mortality in LDLT recipients.Fluid overload (FO) has been shown to adversely affect multiple organs and survival in critically ill patients. Liver transplantation (LT) carries the risk of massive transfusion, which frequently results in FO. We investigated the association of postoperative weight gain with graft failure, early allograft dysfunction (EAD), and overall mortality in LT. 1833 living donor LT (LDLT) recipients were retrospectively analysed. Patients were divided into 2 groups according to postoperative weight gain (<3% group [n = 1391] and ≥3% group [n = 442]) by using maximally selected log-rank statistics for graft failure. Multivariate Cox and logistic regression analyses were performed. The ≥3% group was associated with graft failure (adjusted HR [aHR], 1.763; 95% CI, 1.248–2.490;  LT recipients may be particularly vulnerable to FO owing to their fragile cardiopulmonary status, resulting in increased complications and prolonged stay in the intensive care unit (ICU)10.Liver transplantation (LT) carries the risk of massive transfusion, which frequently results in fluid overload (FO). There is growing evidence that FO can be harmful to critically ill patients or those undergoing major abdominal surgery12. Meanwhile, FO has been reported to have adverse impacts on multiple organ systems14. FO may cause endothelial dysfunction and bacterial or endotoxin translocation, leading to a state of systemic inflammation16, which may result in decompensation and multiorgan failure in advanced liver cirrhosis patients17. Systemic inflammation may also provoke hepatic angiogenesis of liver transplants, leading to fibrosis and cirrhotic remodelling that ultimately result in decreased graft survival in LT recipients20.Graft survival after LT has been found to be associated with various factors, including donor and recipient age, model for end-stage liver disease (MELD) score, and ischaemic timeDespite the link between FO, inflammation, and organ or graft dysfunction, the impact of perioperative FO on graft function in LT recipients has not been well elucidated. Therefore, we investigated the relationship between early postoperative weight gain and the occurrence of graft failure in living donor LT (LDLT) recipients. We also evaluated the occurrence of early allograft dysfunction (EAD), as well as overall mortality.This retrospective observational study was approved by the Institutional Review Board of Asan Medical Centre , which did not require written informed consent due to the retrospective design of the study. All methods were performed in accordance with the relevant guidelines and regulations.All patients who underwent LT at our institution, from January 2008 to September 2015, were enrolled. The Hospital Based Organ Procurement Organization designated by law procured living or deceased liver grafts, and none of the grafts were obtained from executed prisoners. We excluded patients (1) who were <18 years old, (2) who underwent orthotopic LT, and (3) whose preoperative serum creatinine level was >1.5 mg/dL. The clinical data of the remaining patients, including demographic data, liver disease, perioperative laboratory data, donor data, intraoperative data containing anaesthetic management and surgical data, and postoperative morbidity and mortality were obtained from the computerized databases  of our institution, and analysed.21. Briefly, we maintained anaesthesia with sevoflurane or desflurane, a mixture of 50% O2 and 50% air, and a continuous infusion of fentanyl. Arterial pressure was monitored using radial and femoral arterial catheters. For advanced haemodynamic monitoring, a pulmonary arterial catheter was inserted and connected to a Vigilance device . According to the patient’s blood pressure and haemodynamics, the attending anaesthesiologist administered either fluid or vasoactive drugs. In cases of low systemic vascular resistance, a continuous infusion of norepinephrine or vasopressin was used to maintain the mean arterial blood pressure either above the preoperative level or 65 mmHg. Intraoperative transfusions of packed red blood cells (pRBCs), fresh frozen plasma (FFP), cryoprecipitate, and apheresis platelets were based on institutional standards adopted from clinical and rotational thromboelastometry guidelines, with the aim of maintaining prothrombin time  <2.0, fibrinogen >100 mg/dL, and platelet counts >30,000/μL.Anaesthesia and haemodynamic monitoring were performed according to our institutional standard23. Because FO may lead to graft congestion, especially in LDLT recipients, LT recipients are weighed every day and their fluid balance is adjusted accordingly. Patients with massive ascites before surgery are managed with a more liberal fluid management strategy to prevent renal dysfunction such as acute kidney injury (AKI).In the postoperative period, our institution’s goal of fluid management is to maintain near-zero fluid balance to minimize weight changes in the ICUPostoperative weight change (%) was calculated using the following formula: ([body weight on the morning after surgery − body weight on the morning before surgery]/body weight on the morning before surgery) × 100.Serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) were routinely measured every morning from the preoperative day to postoperative day (POD) 7. Serum CRP level was measured using a latex-enhanced immunoturbidimetric assay on the Cobas 8000 analyser , with the CRPL3 reagent (Roche). The diagnostic range of this assay is 0.03 to 35 mg/dL, with a reference value of <0.6 mg/dL. NLR is a marker of systemic inflammation that can be easily obtained from the differential white blood cell count. The NLR was obtained by dividing absolute neutrophil counts by absolute lymphocyte counts.24. Graft failure and overall mortality were assessed using electronic medical records and a registry that was regularly updated by the Asan Organ Transplantation Centre. In addition, the prevalence of pulmonary complications or AKI after LDLT was assessed. According to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, AKI was defined as an increase in serum creatinine by ≥0.3 mg/dL within 48 hours or an increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days25.The main outcome of this study was the occurrence of graft failure after LDLT. Graft failure was defined as the earlier of re-transplantation or death from any cause. Other outcomes included EAD, overall mortality, and lengths of ICU and hospital stay. EAD was defined by the presence of one or both of the following variables: bilirubin >10 mg/dL or prothrombin time (INR) >1.6 on POD 7Continuous variables are reported as mean ± standard deviation or median (interquartile range [IQR]), and categorical variables as frequency (percentage). Between-group comparisons were performed using the Student’s t-test or Mann-Whitney U-test for continuous variables, and the chi-square test or Fisher’s exact test for categorical variables, as appropriate.27. This package tests all possible cutpoints to identify the cutpoint where the maximum of the log-rank statistics is achieved. All patients were classified into 2 groups according to the cutpoint that best discriminates the patients for overall graft survival and failure. The association between postoperative weight change and clinical outcomes after LDLT was evaluated using Cox or logistic regression models. Variables with P-values < 0.1 in univariate analyses were entered into multivariate analyses. Multivariate Cox regression analysis was used to assess the factors associated with graft failure and overall mortality. Multiple logistic regression analysis was used to identify the factors associated with EAD. A backward elimination process was used to develop the final multivariate model, and adjusted hazard ratios (aHRs) or adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. The cumulative graft and patient survival rates were calculated using the Kaplan-Meier method, and log-rank tests were used to evaluate the differences between groups.We used maximally selected log-rank statistics from the Maxstat R package to determine the optimal cut-off value of postoperative weight change (%) predicting graft failure after LDLTth, 27.5th, 50th, 72.5th, and 95th percentiles, as suggested by Harrell)28; fully aHRs with 95% CIs were plotted against postoperative weight change.In addition, the potential nonlinear relationship between postoperative weight change and risk of graft failure was assessed in a multivariate Cox regression model, in which postoperative weight change was modelled with restricted cubic splines with 5 knots  and R 3.5.1  were used for data manipulation and statistical analyses.All reported A total of 1833 adult LDLT recipients were included in the final analysis . Postoperative weight gain ≥3% was associated with a significantly higher rate of graft failure  in the univariate Cox proportional hazards model. Other variables related to graft failure are presented in Table P = 0.001). Kaplan-Meier survival analysis revealed that the ≥3% group had a significantly higher incidence of graft failure than the <3% group   in the <3% group and 12.7% (n = 56) in the ≥3% group (01) Fig. .Table 2CP-values < 0.1 in univariate Cox analysis were selected and included in the final model, which is shown in Fig. P = 0.015).In addition, we analysed the nonlinear relationship between postoperative weight change (%) and the risk of graft failure by entering postoperative weight change modelled with restricted cubic splines in a multivariate Cox regression model. This model was adjusted for all variables in Table P = 0.038) (Table P = 0.005). Kaplan-Meier survival analysis revealed that the ≥3% group had a significantly higher overall mortality rate than the <3% group   and hospital stay  than the <3% group. In addition, we tested our hypothesis with postoperative weight gain cut-off value of 5%  Fig. . The ≥3%P = 0.658), pneumonia , and acute respiratory distress syndrome  between the postoperative weight gain <3% and ≥3% groups. In addition, no difference was found in the incidence of AKI according to the KDIGO criteria  between the two groups.There was no difference in the pulmonary complication rates such as pulmonary edema  had significantly higher risks of graft failure, EAD, and mortality before and after multivariable adjustment.32. Dehydration can lead to dysfunction of vital organs, and adequate fluid administration is essential for maintaining optimal cardiac output, tissue perfusion, and oxygen delivery34. However, FO has also been reported to be detrimental by affecting multiple organ systems14, resulting in postoperative complications, prolonged hospital stay, and increased mortality in critically ill patients or those undergoing major abdominal surgery6. Our findings suggest that even a mild degree of FO may be harmful for graft or patient survival in LDLT, making it prudent to avoid postoperative weight gain ≥3% in these patients.Although fluid therapy plays an important role in perioperative care, the optimal approach for fluid administration in patients undergoing major surgery is still controversial9. In a previous study, the total volume of intraoperative fluid administration was found to be associated with adverse outcomes  in LT recipients8. After adjusting for age, liver disease severity, intraoperative transfusion volume, inotropic use, and operation time, the volume of intraoperative fluid administration was still independently associated with adverse outcomes. In another study of 1197 LT recipients, a negative correlation was observed between ICU readmission and graft or patient survival9. In the subgroup analysis of 53 LT recipients in that study, intravascular FO was suspected to be a significant factor for decompensation leading to ICU readmission in the recipients. Our study is in line with the above studies that addressed the deleterious effects of FO on post-LT outcomes. Moreover, our findings further identified the direct relevance of FO to post-LT graft failure in LDLT recipients.In LT recipients, only a few studies have addressed the association between fluid administration and graft or patient survival15. This is reflected by postoperative weight gain, an indirect measure for the interstitial fluid shift, which leads to bacterial translocation, elevated endotoxin levels, and systemic inflammation16. Furthermore, pathologic inflammation and endothelial dysfunction are known to promote angiogenesis, fibrogenesis, cirrhosis, and increased hepatic resistance, ultimately resulting in portal hypertension and decreased effective hepatocyte perfusion with the risk of liver failure35. Specifically, CRP has been reported to be associated with extracellular volume expansion36 and to have a direct role in endothelial activation and atherosclerosis formation38. Elevated levels of CRP  have been found to be associated with inferior graft survival rates; increased intimal thickening and stenosis after arterial allograft transplantation39, higher risk of EAD and mortality after LT40, higher risk of coronary artery disease progression and graft failure after heart transplantation38, and rapid deterioration of graft function after renal transplantation41.FO may be causally linked to the development of graft failure in LT recipients. Perioperative acute hypervolaemia may destroy the endothelial surface layer along with the inevitable damage caused by surgical trauma , leading to pathologic shifts of fluid and protein towards the interstitium41, the postoperative weight gain ≥3% group had significantly greater mean CRP levels from POD 2 and significantly higher risks of EAD, graft failure, and mortality than the postoperative weight gain <3% group. Previous studies have reported that patients who gain at least 2.5–3 kg of body weight after major abdominal surgery have poorer clinical outcomes than those who maintained a state of zero fluid balance31. Our findings also suggest that even a mild postoperative weight gain could be associated with inferior graft and patient survival after LT. However, considering the potential harmful effects of volume depletion on other organs, a negative fluid-balance might also have adverse effects in LT recipients. Therefore, we presume that careful fluid administration  would be necessary in LDLT recipients for maintaining normovolaemia, to ensure adequate perfusion of multiple organs and at the same time to avoid postoperative weight gain42.In this study, in agreement with the above studies that elaborated the association between FO, inflammation, and organ or graft dysfunction44. Preoperative BNP level has also been found to be an independent predictor of post-LT ICU mortality45. Therefore, our findings of the factors associated with graft failure are in line with previous findings.Patient or graft survival after LT has been reported to be inversely related to older donor age, older recipient age, acute liver failure, and higher RBC transfusion requirementsThis study has some limitations. Because of the retrospective design, the effects of confounding factors on post-LT graft failure could not be completely ruled out. Further, although a causal relationship between postoperative weight gain and graft failure could be inferred based on the physiology or previous studies, it could not be confirmed. Additionally, because the data were collected from a single centre, idiosyncrasies of local surgical and perioperative management of patients may have affected clinical outcomes. Therefore, large-scale multicentre prospective studies are needed to confirm the causal relationship between postoperative weight gain and graft failure in LDLT recipients.In conclusion, the results of this large observational study suggest that early postoperative weight gain may be associated with systemic inflammation and deterioration of graft function in LDLT recipients. Additionally, postoperative weight gain ≥3% (as opposed to weight gain <3%) was associated with significantly higher risks of EAD and mortality after LDLT.Supplementary information


Cricket is a popular sport played by 2.5 billion people of all ages and abilities. However, cricket participation is decreasing in the UK, despite an increased focus of governments on increasing sport participation to enhance public health. Understanding the health benefits and mitigating the health risks of cricket participation may help cricket organisations promote cricket participation while optimising the long-term health of cricket participants. Currently, there is no literature review on the relationship between cricket participation, health and well-being; thus, this relationship remains unclear. Therefore, the aims of this scoping review were (1) to investigate the relationship between cricket participation, health and well-being and (ii) to identify the research gaps related to cricket, health and well-being.Due to the broad nature of our research question and the large number of health outcomes assessed within the cricket literature and to facilitate identification of research gaps, a scoping review methodology was used. The methodology of this paper was informed by previous scoping review protocols and best practice methodological frameworks. MEDLINE, CINAHL, Embase, Scopus, PsycINFO, SPORTDiscus, Cochrane Library, EBSCO, Web of Science and PEDro and grey literature sources  will be systematically searched. Studies that assess a construct related to health and/or well-being in current and/or former cricketers from all ages and standards of play will be eligible. Two reviewers will independently screen full texts of identiﬁed studies for eligibility and will perform data extraction. Results will be presented in tabular and graphical forms and will be reported descriptively.This research is exempt from ethics approval due to the data being available through published and public available resources. Results will be published in a peer-reviewed sports and exercise medicine journal regardless of positive or negative findings. In addition, results will be disseminated through multiple platforms, including conference presentations and social media using multimedia resources , to engage stakeholder groups, including cricketers, cricket coaches, sporting bodies, sports medicine professionals and policy makers. There findings will inform clinical decision making, policy changes and future research agendas. Scoping reviews are a scientifically validated method to answer broad research questions and are the best methodology to provide an overview of all literature investigating the relationship between cricket participation, health and well-being.This scoping review will include grey literature to increase the scope and breadth of the review and screening process.Individual article data will be meta-aggregated to explore emergent themes, with potential to provide new insights and inform future research.Specific articles cannot be analysed for methodological risk of bias, decreasing the interpretability of the results.Cricket is a popular sport with approximately 2.5 billion people of all ages and abilities participating.Over 31% of all adults worldwide are physically inactive, with physical inactivity levels ranging from 17% in Asia to 43% in North America.The link between sport participation and beneficial health outcomes has been synthesised in previous systematic reviews for golf, cycling, and sport and dance.No patients were involved in the design or planning of this study. However, findings from two qualitative studies investigating the relationship of physical activity and quality of life in former elite cricketersThe purpose of a scoping review is to describe all available evidence underpinning a given research question, drawing on research from all possible sources; consequently, scoping reviews are broad in nature. This is in comparison to a systematic review that can only investigate one specific topic; as a result, a scoping review methodology was commenced.what is known about the relationship between cricket participation, health and well-being?The general research question was developed through exploration of the literature, multidisciplinary group discussions and collaboration with experts in cricket. To reflect the context, content and the population included in the review,A preliminary search was conducted on the major clinical and grey literature databases.The titles and abstracts of these 28 articles were then analysed for relevant search terms. The preliminary search identified a large number of irrelevant studies involving cricket insects and cadaveric or in vitro investigations; consequently, the search terms were updated to exclude articles with cadaver* or ‘in situ’ or ‘in vitro’ or ‘insects’ in the title and/or abstract. The final search strategy was created to keep the search broad for greatest inclusion while excluding specific irrelevant studies identified through the preliminary search. A medical librarian assisted by ensuring the search syntax was appropriate for each database.cricket* NOT ’  will be electronically searched. Google Scholar, ClinicalTrials.gov, ISRCTN Registry and ProQuest Dissertations & Theses Global will be searched for grey literature. The search strategy will be as follows: ‘nsects)’ . Article10.1136/bmjopen-2019-032070.supp1Supplementary dataInclusion and exclusion criteria are listed in Titles and abstracts will be screened by the lead author (GSB) for eligibility, and full-text articles will be retrieved and screened by the same author (GSB) against the inclusion/exclusion criteria. A second author (NKP-P) will complete the same screening process on a random sample of 10% of the articles.Data extraction procedures will follow best systematic review practice guidelines.Descriptive data and key findings will be collated and summarised for descriptive analysis, and the results will be presented numerically and thematically. Individual specific study quantitative and qualitative data and thematic data will be grouped into each a priori theme. Following the grouping of articles into each a priori theme, individual article data will be meta-aggregated to explore potential emergent themes.This research is exempt from ethical approval since it is a review of previously published articles.This scoping review of cricket health and well-being is novel and will provide an overview of associations between cricket, health and well-being. Further, key research priorities relevant to stakeholders in cricket, including policy makers and sports governing bodies, will be clarified by this work.Results will be published in a peer-reviewed sports and exercise medicine journal, with open access to increase information dissemination, regardless of positive or negative findings of the relationship between cricket participation, health and well-being. In order to enhance knowledge translation of the findings, a multimodal approach will be used for dissemination. Findings will be presented at conferences, and multimedia resources  will be created to disseminate findings via various social media platforms and through media release.The aims and methodological study design were created in concordance with cricket stakeholders  in order to have a greater understanding of the relationship between cricket participation, health and well-being. Scoping reviews are a scientifically validated method to answer broad research questions and summarise the knowledge gaps in this field. This scoping review will inform individuals and other stakeholders about the risks and benefits of cricket participation at all ages and standards of play. These findings may inform clinical decision making, policy changes and future research agendas.