A multidisciplinary approach has been recommended for the management of patients with infective endocarditis. We evaluated the impact of multidisciplinary case conferences on morbidity, mortality, and quality of care for these patients.We conducted a quasi-experimental study of consecutive patients admitted for infective endocarditis before  and after  implementation of case conferences to discuss medical and surgical management. These occurred as face-to-face discussions or electronically (for non-complex patients), and included physicians from cardiac surgery, cardiology, critical care, infectious diseases and neurology. We assessed process-of-care and clinical outcomes, with the primary outcome being complications up to 90 days after hospital discharge.A case conference was held for 80/80 (100%) of patients in the post-intervention group. After the intervention, more patients received inpatient cardiology assessment , and more patients with definite infective endocarditis underwent cardiac surgery treatment . All pre-intervention and post-intervention patients received guideline-concordant antimicrobial therapy. There was no difference in rates of complications  or mortality up to 90 days after hospital discharge . In multivariable analyses, the intervention was not associated with differences in mortality  or a composite measure of complications and mortality .We successfully implemented a standardized multidisciplinary case conference protocol for patients with infective endocarditis. This intervention had no detectable effect on complications or mortality. Infective endocarditis is generally fatal if untreated. Management requires intensive medical and surgical intervention , 2, and Recent guidelines by the European Society of Cardiology, American College of Cardiology and American Heart Association have recommended a collaborative approach to the management of infective endocarditis , 2, withWe established a multidisciplinary working group that participated in individualized case conferences on patients with infective endocarditis, advising on diagnosis and management according to best available evidence and clinical judgment. The objective of this study was to evaluate the impacts of this team-based approach on quality of care process measures and clinical outcome measures, including complications and mortality.This study was a quasi-experimental before-after study conducted at Sunnybrook Health Sciences Centre (SHSC), a tertiary acute care teaching hospital in Toronto, Ontario, Canada. It was divided into two periods: pre-intervention, prior to implementation of the case conference protocol (October 1 2013–October 12 2015), and post-intervention, after implementation of the protocol (October 13 2015–November 30 2017). The study duration was selected based on resources available for data collection in the pre-intervention period, and the desire to match that 2-year period with a similar duration post-intervention. We anticipated approximately one admission of infective endocarditis per week based on prior experience at our centre.We established a working group consisting of a member from each of the cardiac surgery, cardiology, critical care, infectious diseases and neurology services. A standardized protocol was established to facilitate case conference implementation , and locWe included all patients admitted to SHSC during the study period who met definite modified Duke criteria or probable criteria with strong clinical suspicion for infective endocarditis . Only unStaphylococcus aureus, Enterococcus spp., viridans group streptococci, Streptococcus bovis/gallolyticus, HACEK organisms). Patients admitted between July 1 2015 and November 30 2017  were identified prospectively by notification from the cardiac surgery, cardiology, infectious diseases or general internal medicine services.Patients admitted between October 1 2013 and June 30 2015 were identified retrospectively. The hospital medical records department was screened for all patients who received an International Classification of Diseases (ICD-10-CM) code for infective endocarditis  in any of their diagnoses. We have previously validated the accuracy of these ICD-10-CM codes in identifying patients with infective endocarditis . AdditioPatient characteristics were abstracted from electronic and paper medical records. This included patient age, sex, route of admission (direct or transfer), and Duke criteria (definite or probable); comorbidities included coronary artery disease, coronary artery bypass grafting, prosthetic valve, unrepaired valve lesion, intracardiac device, past history of infective endocarditis, intravenous drug use, intravenous instrumentation , hypertension, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver disease, chronic obstructive pulmonary disease and malignancy. We documented clinical features at admission, including heart failure, neurologic emboli, non-neurologic emboli and mycotic aneurysm. Microbiologic etiology was determined by microorganisms isolated from blood cultures or operative specimens. We also recorded endocardial involvement on echocardiography, including valves or devices affected, maximum vegetation diameter, vegetation hypermobility, valve disruption, abscess and fistula.We examined two types of process measures to assess the fidelity of the intervention. Protocol adherence measures included holding of a working group discussion (electronic or face-to-face case conference), days to face-to-face case conference from hospital admission (for patients for whom there was a face-to-face meeting), formulation of a treatment recommendation, and entry of the recommendation into the electronic medical record. Hospital care measures included assessment by cardiac surgery, cardiology and infectious diseases consultation services following admission, cardiac surgery procedure , days to cardiac surgery from admission, and follow-up by cardiac surgery, cardiology and infectious diseases services after discharge. We also evaluated the appropriateness of antimicrobial choice and duration, based on microbiologic etiology and relevant patient factors ; appropriateness was defined as concordance with American Heart Association guidelines .Clostridium difficile colitis), and was assessed by one investigator via review of post-discharge records. Patient characteristics, process measures and outcomes were abstracted with a standardized case report form .The primary clinical outcome was a composite measure of complications that were new or worse from admission and assessed up to 90 days after hospital discharge, defined as congestive heart failure, ischemic stroke, hemorrhagic stroke, non-neurologic emboli, mycotic aneurysm, new arrhythmia, unexpected (i.e. post-admission and not associated with cardiac surgery) or prolonged critical care admission , or renal replacement therapy. Secondary outcomes  included all-cause mortality, all-cause readmission, attributable readmission, and relapse of infective endocarditis, as well as hospital mortality and total length of hospital stay during the index admission. Outcomes following discharge were obtained from the patient’s electronic medical record, which records follow-up at the study hospital but not at other hospitals or with community-based physicians. Patients without any records post-discharge were deemed lost to follow-up. Attributable readmission was defined as being secondary to a complication of infective endocarditis  or the index admission .We performed descriptive analyses of the pre-intervention and post-intervention groups, comparing them by demographic characteristics, comorbidities, clinical presentation at admission, microbiologic etiology and endocardial involvement. Protocol adherence measures were described for the post-intervention group. Hospital care measures and patient outcomes were compared between the pre-intervention and post-intervention groups. Discrete variables were reported as frequencies with percentages and compared using Fisher’s exact test. Continuous variables were reported as medians with interquartile ranges and compared using the Wilcoxon rank sum test. In addition, multivariable logistic regression analyses were conducted to determine the effects of the intervention on all-cause mortality up to 90 days after hospital discharge, as well as a composite measure of mortality and complications. Age, We performed a sensitivity analysis limited to patients who met definite modified Duke criteria. We also conducted an analysis limited to patients in the post-intervention group, comparing those who had electronic discussions with those who had face-to-face case conferences.All analyses were performed with Microsoft Excel  and R statistical software version 3.2.2 .This study was approved by the Sunnybrook Health Sciences Centre Research Ethics Board, which waived the requirement for informed consent.S. aureus (25.4%) and Enterococcus spp. (16.4%). Native valve involvement was identified on echocardiography in 61.0% of cases, with the mitral valve being most commonly affected (37.3%). Microbiologic etiology and valvular involvement were similar between the two periods, with greater intracardiac device-associated infective endocarditis in the post-intervention group .During the study period, 177 patients with infective endocarditis were admitted to SHSC, with 97 patients in the pre-intervention group and 80 patients in the post-intervention group. The characteristics of the included patients are shown in A case conference was held for 80/80 (100%) of patients in the post-intervention group, with 49 (61.3%) conducted electronically and 31 (38.8%) conducted in person . Every wMore patients received formal inpatient assessment by the cardiology consult service (independent of face-to-face case conferences) during the post-intervention period  . There wAmong our entire cohort, 82/177 (46.3%) patients experienced complications after admission to hospital and up to 90 days after hospital discharge . There wAnalyses limited to patients with definite infective endocarditis by Duke criteria yielded results similar to the main analysis  Tables. Analyses limited to the post-intervention group demonstrated that patients who underwent face-to-face case conferences were younger and more likely to have definite infective endocarditis . There wOur study demonstrates the implementation of a multidisciplinary case conference protocol for patients with infective endocarditis at one academic centre. After implementation, a face-to-face or electronic case conference discussion was held for all patients, which yielded a consensus recommendation on antimicrobial treatment and operative versus non-operative management. Younger patients and those with definite infective endocarditis were more likely to undergo face-to-face case conference than electronic discussion. All patients before and after the intervention received infectious diseases consultation and guideline-concordant antibiotic treatment, but the intervention led to more patients receiving inpatient cardiology assessment and a trend towards more patients having cardiac surgery. There were no detectable effects on overall or individual complications or mortality. Among patients with definite infective endocarditis, the intervention was associated with an increased probability of patients having cardiac surgery, but no significant reductions in complications or mortality.The hospital and 90-day post-hospital discharge mortality rates at our centre are similar to published data , 8, but Three prior studies have evaluated multidisciplinary approaches to the management of infective endocarditis, and all found significant reductions in hospital mortality after implementation: 12.7% to 4.4% ; 28% to Prior to the implementation of case conferences, management of patients with infective endocarditis at our centre generally involved separate services acting independently as consultants. Our quality improvement initiative achieved several objectives: it formalized coordination among these specialties and provided the admitting service with a consensus recommendation to guide treatment; it increased the cardiac surgery rate; and it facilitated assessment by a cardiologist. However, areas for improvement remain. Recommendations were made for all patients in the post-intervention group, but more than 30% were not formally documented into the electronic medical record. Although such cases likely involved verbal communication of the recommendation to the admitting physician, a standardized process for record entry should be established, especially for electronic discussions. The median time from admission to face-to-face case conference was four days, which may be inadequate in cases requiring emergent or urgent surgery. However, all face-to-face case conferences were preceded by an electronic discussion that often resulted in a preliminary consensus on management.Our study has several limitations. Data collection was retrospective for most of the pre-intervention period, which may have led to underestimation of comorbidities and complications due to incomplete chart documentation. Outcomes and follow-up after discharge were collected from the patient’s electronic medical record, but unreported complications were considered absent, and follow-up with physicians at other hospitals and community-based physicians could not be ascertained. Although uniform in-person follow-up would have improved detection of complications, it was not feasible for the retrospective phase of our study and for patients transferred from other institutions. Given that all patients received an infectious diseases consultation and guideline-concordant antimicrobial therapy at baseline, our intervention may have had limited potential to improve outcomes. Another limitation was the discussion of non-complex patients electronically, which may have had a lesser effect compared to face-to-face case conferences. We also did not record time to first e-mail correspondence, for both electronic discussions and face-to-face case conferences. Lastly, the short duration and small sample size may have limited the study’s ability to detect differences in patient outcomes. Since the primary objective of the intervention was process improvement, and sample size was limited by unique cases of infective endocarditis at our centre, the study was underpowered for clinical outcomes. Therefore, given that patients with infective endocarditis are heterogeneous in microbiologic etiology, endocardial burden and comorbidities, a larger population followed over a longer duration in multiple centres would be helpful to establish changes in outcome arising from this form of multidisciplinary intervention.In summary, we implemented multidisciplinary case conferences for patients with infective endocarditis. Participation among the involved specialties was sustained through the 24-month post-intervention period, with a consensus recommendation made for all patients. However, our intervention was not associated with changes in patient morbidity and mortality. Our experience can be used to guide the development of local protocols for team-based models at other centres. Further prospective studies, with greater sample sizes and study durations, would be helpful to confirm the utility of a multidisciplinary approach for infective endocarditis, establish procedures to facilitate implementation, and identify new strategies to improve patient outcomes.S1 Fig(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S5 Table(PDF)Click here for additional data file.S6 Table(PDF)Click here for additional data file.S7 Table(PDF)Click here for additional data file.S8 Table(PDF)Click here for additional data file.


As an important type of post-translational modification (PTM), protein glycosylation plays a crucial role in protein stability and protein function. The abundance and ubiquity of protein glycosylation across three domains of life involving Eukarya, Bacteria and Archaea demonstrate its roles in regulating a variety of signalling and metabolic pathways. Mutations on and in the proximity of glycosylation sites are highly associated with human diseases. Accordingly, accurate prediction of glycosylation can complement laboratory-based methods and greatly benefit experimental efforts for characterization and understanding of functional roles of glycosylation. For this purpose, a number of supervised-learning approaches have been proposed to identify glycosylation sites, demonstrating a promising predictive performance. To train a conventional supervised-learning model, both reliable positive and negative samples are required. However, in practice, a large portion of negative samples (i.e. non-glycosylation sites) are mislabelled due to the limitation of current experimental technologies. Moreover, supervised algorithms often fail to take advantage of large volumes of unlabelled data, which can aid in model learning in conjunction with positive samples .http://glycomine.erc.monash.edu/Lab/GlycoMine_PU/) to facilitate community-wide efforts for accurate prediction of protein glycosylation sites.In this study, we propose a positive unlabelled (PU) learning-based method, PA2DE (V2.0), based on the AlphaMax algorithm for protein glycosylation site prediction. The predictive performance of this proposed method was evaluated by a range of glycosylation data collected over a ten-year period based on an interval of three years. Experiments using both benchmarking and independent tests show that our method outperformed the representative supervised-learning algorithms (including support vector machines and random forests) and one-class learners, as well as currently available prediction methods in terms of F1 score, accuracy and AUC measures. In addition, we developed an online web server as an implementation of the optimized model (available at The proposed PU learning approach achieved a competitive predictive performance compared with currently available methods. This PU learning schema may also be effectively employed and applied to address the prediction problems of other important types of protein PTM site and functional sites. Glycosylation is among the most ubiquitous and important type of post-translational modification (PTM) across three domains of life, including Eukarya, Bacteria, and Archaea . It is estruct . Note that in the case that all δ(xS) = 0, eq. .The original PAly small , 75. Recly small , 74, 75,selected completely at random’ assumption in order to handle general classification tasks, with no requirement to provide prior probability.Based on Bayes’ theorem and the conditional independence assumption, PNB was initially devised based on a multinomial model of naïve Bayes (NB) for text classification . This alnDE (n = 1) that relaxes the attribute independence assumption by using one super-parent attribute and considering all other attributes as conditionally independent, given this super-parent. Similarly, the proposed PAODE algorithm  is a special version of PAnDE, where n = 1.PAODE  was propPTAN is a another version of the tree-augmented NB (TAN)  algorithPFBC was proposed based on full Bayesian network classifier (FBC) , where tIn this study, we compared the predictive performance of our newly proposed PA2DE (V2.0) algorithm with the other five Bayesian PU-learning algorithms PA2DE, PNB, PAODE, PTAN, and PFBC for predicting glycosylation and further compared its predictive performance with several supervised-learning and one-class classification algorithms.Two representative supervised-learning algorithms, RF and SVMs were used to compare the predictive performance of PU-learning and one-class classification algorithms. These two algorithms have been widely used to solve a variety of bioinformatics tasks and also in protein glycosylation prediction , 80–83 wOne-class classification algorithms identify samples of a specific class by learning from a training set containing samples only from this class. One-class classification has been widely applied in a variety of real-world scenarios, such as outlier  and novePrecision and Recall in (5) are respectively defined asTP, TN, FP, and FN represent the numbers of true positives, true negatives, false positives, and false negatives, respectively.Three performance measures were employed to evaluate the predictive performance of the supervised- and PU-learning schemes and facilitate comparisons between different methods, including AUC, F1, , 70 and


Aim: Hamstring muscle injury is the main injury related to sports requiring sprint acceleration. In addition, hamstring muscles have been reported to play a role in horizontal force production during sprint acceleration performance. The aim of the present study was to analyze (i) the determinants of horizontal force production and (ii) the role of hip extensors, and hamstring muscles in particular, for horizontal force production during repeated sprint-induced fatigue conditions.Method: In this experimental laboratory setting study including 14 sprint-trained male athletes, we analyzed (i) the changes in sprint mechanics, peak torque of the knee and hip extensors and flexors, muscle activity of the vastus lateralis, rectus femoris, biceps femoris, and gluteus, and sagittal plane lower limb motion, before and after twelve 6-s sprints separated by 44 s rest on an instrumented motorized treadmill, and (ii) the determinants of horizontal force production (HF) during the sprint acceleration in a fatigue state (after 12 sprints).Results: The repeated-sprint protocol induced a decrease in maximal power output (Pmax)  and in the contact-averaged horizontal force component (HF)  but not meaningful changes in the contact-averaged resultant  force (TotF)  and vertical force component (VF) . A decrease was found in concentric peak torque of the knee flexors and extensors and in gluteus and vastus lateralis muscle activity during entire swing and end-of-swing phase. An increase was found in contact time and swing time, while step frequency and knee speed before ground contact decreased. Muscular determinants associated with HF and its decrease after the repeated-sprint protocol were concentric peak torque of the hip extensors (p = 0.033) and a decrease in gluteus maximus activity at the end-of-swing (p = 0.007), respectively.Conclusion: Sprint-induced fatigue lead to changes in horizontal force production muscular determinants: hamstring muscle seems not to have the same role than in non-fatigue condition. Horizontal force production seems to be more dependent on the hip extensors and gluteus maximus function. Given the fatigue-induced decrease in hamstring muscle strength, we can hypothesize that muscle compensatory and kinematic strategies reported in a fatigued state could be an adaptation to allow/maintain performance and a protective adaptation to limit hamstring muscles constraints. Hamstring muscle injury (HMI) is, despite improvements in knowledge and prevention strategies, the main injury related to sport requiring sprint acceleration, such as football , 2016, rThe majority of HMIs occur during sprinting actions, for example for sprinters at or near top speed , or in fgluteus maximus and hamstring muscles) play a key role in this horizontal force production  has been shown to be a stronger determinant of field sprint performance than the overall magnitude of vertical or resultant GRF . Hip extoduction , and theoduction . Concretoduction . In addioduction . In addioduction . Coherenoduction , 2016. Ion phase . Thus, fIn addition to the mechanical and muscular determinants of HMI occurrence in sprinting, another parameter comes into the equation: fatigue. Indeed, injuries do not only occur during the initial sprints. Since team sports matches are associated with muscular fatigue , and sinTotF) and an even larger relative decrease in horizontal force component (HF). However, it is unknown whether this decrease in HF is explained by the decrease in hamstring strength or other mechanisms. To our knowledge, experimental studies exploring the influence of fatigue (In match-induced fatigue conditions  or after fatigue  (i) did Furthermore, since muscle fatigue is task-specific , it is oThus, the aim of the present study was to analyze (i) the determinants of the sprint acceleration performance and horizontal force production and (ii) the role of hip extensors, and hamstring muscles in particular, for the horizontal force production, in repeated sprint-induced fatigue conditions.This was an experimental laboratory setting, cross-sectional study analysing sprint mechanics, isokinetic PT of knee and hip extensors and flexors, muscle activity and sagittal plane lower limb motion, before and after twelve 6-s sprints on an instrumented motorized treadmill. The study was approved by the institutional ethics review board of the Faculty of Sport Sciences, and conducted according to the Declaration of Helsinki II.Fourteen male subjects (body mass (mean ± SD): 79.9 ± 7.9 kg; height 1.79 ± 0.07 m; age 24.2 ± 4.6 years) trained for sprint running  volunteered to participate in this study. All subjects trained at least three times a week since more than 3 years, and were free of musculoskeletal pain or injuries at the time of the study and in the six previous months. Written informed consent was obtained from the subjects.A familiarization session for treadmill sprints and isokinetic tests was performed approximately 1 week prior to the testing session. After a standardized warm-up described below, subjects repeated short (<5 s) treadmill sprints at increasing intensities, with full recovery and until being comfortable with the running technique required . Following this, the subjects performed a familiarization session with the isokinetic test procedure for the knee flexors (KFlex) and extensors (KExt) and hip flexors (HFlex) and extensors (HExt), following the isokinetic testing procedure described below, during which they were encouraged to perform at their best.-1 running, followed by 5 min of sprint-specific hamstring warm-up exercises, and three progressive 6-s sprints at increasing velocities separated by 2 min of passive rest. Subjects performed the isokinetic warm-up followed by maximal isokinetic strength measurements of KFlex, KExt, HFlex, and HExt. Thereupon, EMG electrodes and reflective markers were placed on the right lower limb. Maximal EMG activity was measured for each muscle group for standardization. Subjects repeated the sprint specific warm-up on the treadmill with two submaximal 6-s sprints. After 5 min of recovery, the subjects performed one maximal 6-s sprint, from which maximal power output (Pmax) was used as the criterion score for the first sprint of the RS performed during the testing session. Indeed, to prevent pacing effects occurring in such RS protocols , following the same standardized procedure after instructions and conducted by the same examiner (PE). PT of KFlex, KExt, HFlex, and HExt was obtained during three maximal repetitions at 120°/s, in concentric and eccentric mode in a randomized order (-1) and agonist-to-antagonist ratios were used. Reliability of each parameter was calculated using maximal data from the familiarization and testing session .Isokinetic strength was measured using a Con-Trexed order . Only thed order . Subjected order , (ii) shed order , and (iied order . For KFled order . The kneed order . For HFled order . The coned order . The dyned order . PT norm session : reliabict in s), aerial time (at in s), swing time (swingt in s) and SF (Hz)] and sprint kinetics .Sprint mechanics were measured during sprints performed on a motorized instrumented treadmill  , rectus femoris (RF), BF and gluteus maximus (Glut) muscles was recorded using bipolar silver chloride surface electrodes of 30 mm diameter  placed on the skin according to recommendations by SENIAM  and foot acceleration before ground contact (in m.s-2).The motion of the right foot and knee was recorded in the sagittal plane of motion with a camera  mounted on a tripod placed 1.5 m away from the treadmill in a lateral view  and JASP .Descriptive statistics are presented as mean values ± SD. Normal distribution of the data was checked by the Shapiro–Wilk normality test. For all sprint mechanics and EMG variables considered, “first sprints” and “last sprints” values were averaged for the first two and last two sprints for each subject, respectively . For isot-tests and standardized differences in means for practical significance with ES threshold values of <0.2, 0.2, 0.6, 1.2, 2.0, and 4.0 to represent trivial, small, moderate, large, very large and extremely large effects, respectively  we used a stepwise multiple regression model including last sprints and post-RS values and percentage of difference between the first and last sprints muscular activity values and between pre- and post-RS muscular PT and ratio values (delta-RS) as independent variables.In order to analyze the determinants of the horizontal force production . There was also a decrease in maxV  and in HF , but not meaningful in TotF  and in VF . There were moderate to large changes in step temporal and kinematics variables with the RS protocol: increase in contact time  and swing time , decrease in SF , decrease in knee speed before ground contact . For muscular aspects, we observed a moderate decrease in KFlex  and KExt  concentric PT, and in gluteus maximus muscle activity during entire swing  and end-of-swing  phases and in vastus lateralis muscle activity during entire swing  and end-of-swing  phases.The comparison of first vs. last sprints and pre-RS vs. post-RS values is presented in Table HF after RS  was post-RS HExt concentric PT (p = 0.033). When explaining the changes in horizontal force production between first and last sprints with stepwise multiple regression model using delta-RS values, the muscular determinant associated with the decrease in HF was the decrease in gluteus maximus activity at the end-of-swing (p = 0.007).When explaining last sprints horizontal force production with stepwise multiple regression model using last sprints and post-RS values, the muscular determinant associated with maxP) and in horizontal force production (HF), which can be considered markers of neuromuscular fatigue, (ii) higher HF in a fatigue state was mainly associated with a higher concentric PT of the hip extensors, (iii) the lower decrease in horizontal force production after fatigue was mainly associated with a lower decrease in gluteus maximus activity at the end-of-swing, and (iv) hamstring muscle torque during knee flexion was not associated with horizontal force production in a fatigue state, contrary to what was observed in the non-fatigue condition (The main findings of the present study were that (i) the RS protocol induced a clear decrease in sprint acceleration performance (ondition .maxP in the fatigue condition. This could be caused by a fatigue-induced decrease (i) in the total amount of force produce by the athletes onto the ground (decrease in TotF), or (ii) in the ability to orient the force in the horizontal direction (represented by HF in the present study), or (iii) both. Since HF decreased with RS while TotF was not meaningfully affected, it is very likely that the decrease in maxP in the fatigue condition was mainly explained by the decrease in force output in the horizontal direction (HF) rather than the total amount of force produced. This is in agreement with a previous study using repeated sprint-induced fatigue  play a relatively more important role in horizontal force production in fatigue condition. Hip extensor function was associated with non-fatigued HF production in the initial part of the acceleration (first 10 steps) (gluteus maximus) may then compensate the potentially altered hamstring muscle function in a synergistic manner.In non-fatigue conditions, hamstring muscles have been reported to play a key role in horizontal force production . In a fa0 steps) . Moreove0 steps)  do not eHF production. Indeed, due to muscle redundancy various neuro-motor strategies may exist to compensate for decreased muscle strength  with either a maximum strength or a muscular endurance emphasis can equally reduce fatigue-induced loss of strength over a football match . In addiThe main strengths of the present study were the experimental design and materials used. The motorized instrumented treadmill used allowed performing realistic sprint accelerations from zero to almost maximal velocity in kinetic conditions that are subjectively and objectively comparable to field linear sprinting . It alsoSome limitations related to the methodology used have previously been discussed , 2015. Ogluteus maximus. Given the decrease in hamstring muscle strength with fatigue, we can hypothesize that muscle compensatory and kinematics strategies reported in fatigue state could be an adaptation to allow/maintain performance and a protective adaptation to limit hamstring muscle constraints. However, in a case of gluteus maximus weakness, this exposes subjects to HMI risk. Although strong conclusions cannot be made, these present results should be used in practice by integrating hip extensors/gluteus maximus strengthening in addition to hamstring knee flexors strengthening, as well as endurance-focused training strategies in addition to maximal performance training, and taking into account the win–win performance-prevention strategy: training for performance can help for injury prevention and vice-versa.This study allows better understanding of the determinants of sprint acceleration performance and horizontal force production in fatigue conditions and the role of the hamstring muscles in such conditions, which presents relevant perspectives in practice given the interest of repeated sprint ability in team sports and the importance of HMIs in sports including sprinting and multiple acceleration. The present results show that the muscular determinants of the horizontal force production change in fatigue state: the hamstring muscles seem not to have the same role than in non-fatigue condition. The horizontal force production seems to be more dependent on the function of the hip extensors and PE, JM, MB, PS, and J-BM conceived and designed the study. PE, PG, PJ-R, PS, and J-BM performed experimentation and data collection. PE, JL, PA, PG, PS, and J-BM analyzed the data. PE, JM, JL, PJ-R, PS, and J-BM interpreted the results. PE, JM, JL, PS, and J-BM drafted the manuscript and prepared the table and figure. PE, JM, JL, PG, PJ-R, MB, PS, and J-BM edited, critically revised the manuscript, and approved the final 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. The handling Editor declared a past co-authorship with one of the authors MB.


Hypertension is a major risk factor for cardio-cerebrovascular disease. Songling Xuemaikang capsules (SXC), a formulation of Chinese herbal patent medicine, has been used as a complementary medicine with conventional western medicine to treat patients with hypertension since 1994 in mainland China. However, the efficacy of treatment with SXC alone against hypertension remains unclear.This is a multicenter, placebo-controlled, double-blinded, randomized controlled clinical trial. A total of 570 patients with low-to-medium risk hypertension are randomized in a 1:1 ratio to receive SXC or placebo three times daily for eight weeks. The primary outcomes are 24-h average systolic blood pressure and average diastolic blood pressure. The secondary outcomes are daytime average blood pressure, night-time average blood pressure, fluctuation of blood pressure, hypertension control rate, traditional Chinese medicine (TCM) syndrome scores, and quality-of-life scores.This is the first multicenter trial conducted to evaluate the efficacy and safety of TCM in patients with low-to-medium risk hypertension. Our study will provide evidence-based results of a complementary preventive measure for hypertension.ChiCTR-IPR-17011383. Registered on 12 May 2017.Chinese Clinical Trial Registry, The online version of this article (10.1186/s13063-019-3308-5) contains supplementary material, which is available to authorized users. Hypertension is the leading risk factor for cardio-cerebrovascular disease and premature death in China . Recent Pueraria lobata, and pearl powder. Studies have shown that puerarin, the main active ingredient of P. lobata, can reduce renin-angiotensin levels, dilate coronary and cerebral arteries, improve microcirculation, reduce vascular remodeling and ventricular hypertrophy, and exhibit anti-platelet aggregation, resulting in the promotion of endothelial cell function and the regulation of vasoactive factors [Conventional antihypertensive agents are usually associated with many adverse effects. Chinese patent medicines, which are important components of traditional Chinese medicine (TCM), have been increasingly accepted by patients with hypertension. Songling Xuemaikang capsules (SXC) are a formulation for oral intake produced by Chengdu Kanghong Pharmaceutical Co. Ltd., with official approval from the China Food and Drug Administration (ratification document number: Sinopharm Z10960023). It comprises fresh pine needles,  factors –11. Acti factors , 13. The factors . Several factors , 16; howThis study aims to determine the efficacy of SXC in patients with low-to-medium risk hypertension.This multicenter, double-blind, randomized, placebo-controlled parallel-group, superiority trial is registered in the Chinese Clinical Trials Registry (ChiCTR-IPR-17011383). It complies with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all patients before their participation in this study; the recruited patients will be randomized to either the SXC group or the placebo group. We will rigorously follow the Consolidated Standards of Reporting Trials (CONSORT) recommendations when reporting the results [The trial will be conducted in seven centers in China. A total of 570 participants will be recruited. After we acquire their consent, the participants will be enrolled in the trial, which consists of a two-week run-in period and an eight-week treatment period.A completed SPIRIT checklist is available as a supplement . The secondary outcomes include daytime average blood pressure, nocturnal average blood pressure, fluctuation of blood pressure (24-h ambulatory blood pressure), fluctuation degree of systolic and diastolic blood pressure, control rate of hypertension (control rate of hypertension = hypertension control number/hypertension number × 100%), TCM syndrome scores, and the 36-item Short Form Health Survey score. The other outcomes include levels of vasoactive substances , four hormones related to hypertension , inflammatory mediators, and blood lipids. Safety outcomes, which include complete blood count, routine urine test, liver and renal function tests, and electrocardiograms, will also be monitored periodically. All adverse events (AEs) will be followed from randomization to the end of the trial. Items to be measured and the time window of data collection are shown in Fig. AEs are defined as negative or unintended clinical manifestations following treatment. Patients will be asked to report to the investigators any abnormal reactions occurring at any time during the trial. In addition, investigators will collect information about abnormal reactions monthly. All details of related and unexpected AEs, such as time of occurrence, degree of AE, and suspected causes, will be recorded on case report forms (CRFs). Moreover, there is a data safety monitoring board to oversee the trial.The schedule for all study procedures for all evaluations is shown in Fig. Participants are randomized in a 1:1 ratio using a computer-generated, site-stratified, block randomization schedule. The study capsules will be labeled with sequential randomization numbers and each patient will be assigned the lowest number available at each participating center. All patients, care providers, and attending physicians will be blinded to treatment assignment until the study is completed. Duplicated blinding codes will be given to the main research institution and the manufacturer; the blinding codes cannot be revealed during the trial.http://www.xyedc.com/). To maintain the quality of data, we will adopt valid measures to ensure information accuracy, integrity, and authenticity. First, computer logic checks will be run to identify items such as inconsistent data, missing data, and questionable values. After that, the supervisor will perform source data verification to check the consistency of the original data. Queries may be issued by the supervisor, which will be answered by the site investigators. Second, manual checks will identify more complicated and less common errors. Third, the supervisor will conduct site visits to compare the electronic database with the source documents. Identified errors will be resolved to ensure data quality. Fourth, the Data Coordination Center will be in charge of data validation.CRFs are being used for data entry and data from all participating centers will be imported into the clinical data management system (P < 0.01) and diastolic blood pressure (DBP)  compared with that by antihypertensive drugs alone [2 = 49, type I error rate (α) = 0.05, and a power of 90% (type II error rate (β) = 0.1), the sample size for one arm needed to be 258, resulting in n = 2 × 258 = 516 . Considering a dropout rate of 10%, a total of 570 patients needed to be allocated to attain the required number of patients for the efficacy analysis.The sample size was calculated based on the expected reduction in hypertension. A meta-analysis has showed that SXC combined with antihypertensive drugs is more effective in lowering both the systolic blood pressure (SBP) .For all analyses, In this trial, we will assess the efficacy and safety of SXC in treating patients with low-to-medium risk hypertension. The present study is designed as a multicenter, double-blind, randomized, placebo-controlled, parallel-group superiority trial that will provide high-powered evidence regarding the efficacy and safety of SXC in treating patients with low-to-medium risk hypertension.A previous study showed that pine needle extract has pharmacological properties that modulate hippocampal excitotoxicity-derived memory impairment under severe stress conditions . In saltFor patients with low-to-medium risk hypertension, the current domestic and foreign guidelines generally recommend lifestyle improvement and monitoring of blood pressure and other risk factors 1–3 months before deciding whether to carry out drug treatment. Therefore, 10 weeks of follow-up monitoring and placebo therapy will not cause irreversible damage to the individuals .There are certain limitations to this study. First, because the study is being performed in Beijing, China, it is uncertain whether the relative effects of the trial drugs would be similar in other ethnic groups. Second, the follow-up period is relatively short.Nevertheless, this trial aims to evaluate the efficacy and safety of SXC for the treatment of patients with low-to-medium risk hypertension.The trial was initiated in July 2017 and is currently open for enrolment; thus far, 120 patients have completed the 10-week follow-up. However, no analysis has been conducted since the commencement of the trial. No serious AEs have occurred to date.Additional file 1:SPIRIT Checklist. (DOC 124 kb)


Acute kidney injury (AKI) is assoicated with high mortality and measures to improve risk stratification and early identification have been urgently called for. This study investigated whether an electronic clinical prediction rule (CPR) combined with an AKI e-alert could reduce hospital-acquired AKI (HA-AKI) and improve associated outcomes.A controlled before-and-after study included 30,295 acute medical admissions to two adult non-specialist hospital sites in the South of England ; all included patients stayed at least one night and had at least two serum creatinine tests. In the second period at the intervention site a CPR flagged those at risk of AKI and an alert was generated for those with AKI; both alerts incorporated care bundles. Patients were followed-up until death or hospital discharge. Primary outcome was change in incident HA-AKI. Secondary outcomes in those developing HA-AKI included: in-hospital mortality, AKI progression and escalation of care. On difference-in-differences analysis incidence of HA-AKI reduced . In-hospital mortality in HA-AKI cases reduced on difference-in-differences analysis  and unadjusted analysis . Mortality in those flagged by the CPR significantly reduced . Outcomes for community-acquired AKI (CA-AKI) cases did not change. A number of process measures significantly improved at the intervention site. Limitations include lack of randomization, and generalizability will require future investigation.In acute medical admissions a multi-modal intervention, including an electronically integrated CPR alongside an e-alert for those developing HA-AKI improved in-hospital outcomes. CA-AKI outcomes were not affected. The study provides a template for investigations utilising electronically generated prediction modelling. Further studies should assess generalisability and cost effectiveness.NCT03047382.Clinicaltrials.org  Acute kidney injury (AKI) is a clinical syndrome, defined through an acute increase in serum creatinine (SCr) and/or reduction in urine volume. However, there is a continuum of injury before sufficient loss of excretory kidney function can be detected with a change in SCr . Up to 2There has been an international call to address deficits in recognition and management of patients with AKI, including early risk assessment at which point interventions could be most beneficial , 4, 5. IThis impact analysis study employed one of the few available externally validated AKI CPRs–the Acute Kidney Injury Prediction Score (APS)—derived in a UK general medical population, which combines data on age, medical history and physiological parameters , 16. TheIn emergency medical admissions, without identifiable AKI at admission, could introduction of an electronically generated AKI CPR reduce the incidence of HA-AKI,In concert with the CPR, does an e-alert for new HA-AKI reduce associated complications including in-hospital mortality, escalation to intensive care and maximal AKI stage,Does identification of a group at high risk of developing HA-AKI improve outcomes,What is the effect of e-alerting community-acquired AKI (CA-AKI) at admission to hospital?Ethical approval was given by NHS Research Ethics Committee London—City Road and Hampstead (REC reference 13/LO/0960) and the study registered with clinicaltrials.org (NCT03047382) (2 prior to admission (in those with an available baseline SCr); baseline SCr was defined using NHS England’s National algorithm [At admission, all in-patients have physiological observations measured and entered via handheld systems into the clinical data software system . Previous ICD-10 coded history , were retrieved and chronic kidney disease (CKD) was defined as an eGFR <60 mls/min/1.73mlgorithm . KDIGO cExclusion criteria:Patients moved directly from the A&E department to the ICU (as neither area uses the Patientrack data system),Aged <18 years,Non-medical  admissions and,Discharged without spending a night in hospital.Patients were followed-up until hospital discharge or in-hospital death  and expert guidance were considered prior to incorporation into the clinical workflow as part of a multi-faceted AKI guideline implementation , 21. TheThe primary outcome to assess the APS CPR was change in incidence of HA-AKI (KDIGO change in SCr) within seven days of hospital admission following intervention when adjusting for baseline differences between intervention and control sites. Other outcomes in those who developed HA-AKI included mortality in-hospital and seven days following admission, maximal increase in AKI KDIGO Stage and in SCr from admission, and ICU escalation. These outcomes were also assessed in patients highlighted by the CPR at high AKI risk (AMBER) and for patients with CA-AKI. Process measures were collected to attempt to explain the effects of the intervention. These included drug prescribing, completion of the suggested care bundles and a notes review of a randomly selected collection of HA-AKI cases.2 tests. T-tests or Mann-Whitney U tests were used to compare continuous variables. Data were extracted fully anonymised on Microsoft® Excel® and all analyses were conducted using SAS (V9.4®).To avoid potential bias due to existing background differences between hospitals and temporal changes, we adopted the difference-in-differences approach by including time variable (before-after) and its interaction with the hospitals –29. All Over the 20-month study period 30,295 admissions were analysed  with a mDifference-in-differences analysis suggested a reduction in HA-AKI at the intervention site . Unadjusted incidence of HA-AKI did not change significantly at the intervention  or control sites  . In patiIn cases of new HA-AKI in-patient mortality, using difference-in-differences analysis, significantly reduced at the intervention site  . UnadjusAt the intervention site, of those flagged as high risk  14% went on to develop HA-AKI vs 5% with no flag (GREEN), P<0.001. Following the intervention, in-patient mortality in this high-risk amber group significantly decreased  with no change at control site . There wThis is the first impact analysis study combining an AKI CPR and an AKI e-alert in hospitalised patients. The intervention was associated with a decrease in the incidence of new AKI but, importantly a significant improval in survival in those individuals who developed HA-AKI was also found. This may reflect a synergistic benefit of highlighting those at risk and de novo AKI, implying best practice would be institution of a care bundle in both groups, in tandem with a multimodal service improvement approach. Other outcome measures including escalation of care and progression of AKI were suggested. There was no change in outcome following introduction of an e-alert for patients with established AKI at admission to hospital, indicating the measures introduced did not affect the underlying disease process.The primary aim of the study was to investigate whether an AKI CPR could prevent HA-AKI. On a difference-in-differences analysis a reduction was achieved. The treatment effect may have been limited due to a lack of specificity in the CPR—in derivation and validation the APS had moderate discrimination (AUROC of 0.65–0.72) and to avoid alert fatigue, only patients with a score ≥5 were alerted to , 16. FurTo date, the only RCT of an AKI e-alert showed no outcome benefit, though the intervention in that study was limited to an electronic link to practice guidelines . In two The majority of studies reporting on the effects of alerts incorporated as part of CDSSs are medication related , howeverautomatic provision of decision support as part of clinician workflow at the time and location of decision-making,provision of recommendations rather than just assessments and,computer based decision support.These factors and others were considered during study design, which provides a proof of concept for future investigations of complex healthcare interventions. Alerts could be quickly acknowledged, with a single alert at admission for those at risk, with a further alert on patients who met AKI criteria within the nursing clinical workflow , 44. A cThis natural experiment introducing an electronic alert intervention at one site within a similar geographical area to a control site allows for unrelated change in disease occurrence and practice, with adjustment for confounders and has been described in previous impact studies , 23. HA-The study took place as part of an information technology service improvement intervention that did not allow for a RCT design, with selection bias a concern. Between sites in both periods overall mortality was higher at the intervention site, as was the rate of HA-AKI, which may reflect differences in co-morbidities and socioeconomic factors. However, the before-after controlled design using difference-in-difference analyses is accepted as a way of detecting the effects of an intervention, and to control for confounders and secular trends , 56. OutThe concept of a continuously learning healthcare system was articulated by the Institute of Medicine in the US as a way of showing how evidence informs practice and vice versa in an iterative process of innovation and collaboration between research, information technology and clinical practice Click here for additional data file.S1 File(DOCX)Click here for additional data file.S1 Protocol(PDF)Click here for additional data file.


Recently, smart wearables, typically as wearable electrocardiogram (ECG), electroencephalography (EEG), electromyography (EMG), blood pressure (BP), photoplethysmography (PPG), heart sound, respiration, sleep, and motion monitoring, have been gaining a significant role in the field of healthcare and are looking to be a big and promising market in the technology industry. They are scientifically and clinically useful for better monitoring of real-time, long-term, and dynamic physiological and pathological processes, thus providing opportunities for the development of new diagnostic and therapeutic techniques. These could be expedient for the management of chronic illnesses, such as cardiovascular disease (CVD), sleep disorders, emotional problems, cognitive impairment, and functional decline, as well as for healthcare applications for special populations, such as for the aged, pregnant women, athletes, and astronauts. The mainstream in smart wearables research is moving towards more sophisticated methodologies based on clinical “big data,” artificial intelligence (AI), advanced signal processing, service robots, and networks, as well as more robust signal acquisition approaches.In this context, many researchers have addressed recent technology advances in signal processing and device development for smart wearables, as well as the implementation of these technologies for clinical applications. The processing and analysis of wearable physiological signals  is a key issue for smart wearable devices. The preliminary work mainly includes dynamic signal quality assessment, signal transformation and decomposition, feature extraction and selection, and the following machine learning-based methods.Y. Ning and colleagues decomposed multichannel surface electromyography (sEMG) signals into their constituent motor unit action potential (MUAP) trains. A combination method of measurement correlation (MC) and linear minimum mean square error (LMMSE) was proposed, named as MC-LMMSE, which was validated on both simulated and experimental electrode array sEMG signals. This study showed that the MC-LMMSE method can extract a relatively large number of MUs with strong robustness to noise.As PPG technology has been widely applied to wearable sensors, L. Wang et al. developed a method for automatically estimating systolic blood pressure (SBP) and diastolic blood pressure (DBP) based only on a PPG signal. In this study, a multitaper method (MTM) was used for feature extraction and an artificial neural network (ANN) method was used for SBP and DBP estimation, obtaining a relatively high accuracy of BP estimation with an absolute error of 4.02 ± 2.79 mmHg for SBP and 2.27 ± 1.82 mmHg for DBP.QRS complex location is important and even essential for ECG signal processing. F. Liu et al. performed a systematic evaluation work on ten widely used and high-efficient QRS detection algorithms, aiming at verifying their performances and usefulness in different application situations, especially in the dynamic noisy ECG environment. Four experiments were carried out on six internationally recognized databases. For the clean clinical ECG signals, the majority of the QRS detectors reported high-level detection accuracies, whereas the accuracy of all algorithms significantly decreased for poor signal quality ECG signals. Thus, some special preprocessing and postprocessing procedures are needed. In addition, the QRS detector needs to be carefully selected in special situations, such as paced rhythm ECGs. This study offers a reference for selecting from the existing algorithms.Clinical applications for chronic illnesses detection, including cardiac arrhythmia, hypertension, heart failure, sleep disorder, emotional problem, cognitive impairment, and functional decline, are the main target. The automatic detection and diagnosis algorithms for special diseases are the soul of clinical application. Typical works included in this special issue are summarized as follows:X. Xu et al. proposed a new framework for automatic atrial fibrillation (AF) beat identification, which combines modified frequency slice wavelet transform (MFSWT) and convolutional neural networks (CNNs). This work achieved a relatively high accuracy of 84.9%. The study indicated that it was possible to accurately identify AF or non-AF ECGs from a short-term signal episode.Obstructive sleep apnea (OSA) is a major breathing-related sleep disorder. Y. Fang et al. proposed a novel sleep respiratory rate detection based on the characteristic moment waveform (CMW) method. This method could detect sleep respiratory rate accurately. In addition, the apnea sections can be detected by the sleep respiratory rate curve with a given threshold, and the time duration of the segmentation of the breath can be calculated for detailed evaluation of the OSA state.D. V. Phan and team evaluated the relationship between daily physical activity (DPA) and memory capacity, as well as the association between daily activity and attention capacity, using spatial span test (SST) and trail making test (TMT). The study showed that the short-term effects of very active time duration (VATD) and calories burnt on the day are significantly and negatively associated with memory and attention capacities of college students.Intelligent health monitoring systems combining wearable technologies for health monitoring and disease diagnosis also aroused widespread concern among researchers.K. Guan et al. designed a remote health monitoring system for the elderly. This proposed system consisted of three parts: smart clothing, a smart home gateway, and a health care server. The system could monitor the ECG signals and motion signals of the elderly, and has the potential to provide long-term and continuous home healthcare monitoring services.For gastrectomy patients requiring dietary support, K. Taniguchi et al. developed a chewing-count measurement device, named wearable reliable chewing-count (RCC), using an earphone-type sensor to display the information on a tablet terminal in real time. This earphone-type RCC measurement device could experimentally distinguish chewing from other actions. It can catch chewing actions and accurately count the number of chews with high probability.Based on a piecewise three-segment sit-to-stand (STS) biomechanical model and a double-sensor difference algorithm, K. Liu and his group proposed an original approach for noninvasive estimation of lower limb joint moments for analysis of STS rehabilitation training with only inertial measurement units. This work presented joint kinematic and kinetic analysis using a customized wearable sensor system composed of accelerometers and gyroscopes. Compared with a referenced camera system, the proposed system was evaluated on five healthy subjects and five patients in rehabilitation. The results showed that the newly developed system was available for spatiotemporal analysis of STS task with fewer sensors and a high degree of accuracy, and can be used as a reference for rehabilitation training or feedback for the control of a powered exoskeleton system.Low power- and energy-efficient hardware is still the obstacle for long-term real-time wearable devices. K. Luo et al. developed a digital compressed sensing- (CS-) based single-spot Bluetooth ECG node to deal with this challenge. Each node consisted of an ultra-low-power analog front-end, a microcontroller, and a Bluetooth 4.0 communication module. A periodic sleep/wake-up scheme and a CS-based compression algorithm were implemented in each node. This scheme can reduce the airtime over energy-hungry wireless links. The energy consumption of the proposed node is 6.53 mJ, and the energy consumption of the radio has a decrease of 77.4%.Overall, the development of smart medical wearables still has far to go, from hardware devices (electrode and sensor design) to data processing and analysis. There is much meticulous work still to be done, including wearing comfort, energy consumption, database annotation, signal quality, building standards, and more. Even for ECG it would be an interesting study to see specifically how a multielectrode system responded to very specific situations, such as movement , body position, and heart rate. It is important to get beyond overall accuracy. Anyway, the gradual improvement of smart medical wearable devices will contribute a tremendous amount of power to human healthcare.


In a recent issue of the BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was reviewed . The review was comprehensive, and included traditional and non-traditional/alternative treatments, including herbal medicines and spirituality. However, evidence showing that classic or serotonergic hallucinogens/psychedelics such as psilocybin and lysergic acid diethylamide (LSD) could be effective treatments for depressive and anxiety disorders in end-stage cancer was not included. In this commentary, we expand the information available on the original article by briefly reviewing data from recent placebo-controlled, double-blind, cross-over clinical trials showing evidence that administration of single (or few) doses of LSD and psilocybin was associated with rapid and sustained reductions in depressive and anxiety symptoms in patients with end-stage cancer and other life-threatening diseases . Since these substances seem to produce rapid and sustained therapeutic effects with single (or few) doses and well tolerated, large-scale, prospective, multi-site studies of end-stage cancer and classical/serotonergic hallucinogens/psychedelics should be performed to improve our understanding of the therapeutic potentials of these drugs and their use on clinical practice. In a recent review article published on BMC Psychiatry, the evidence of effectiveness of treatments for psychiatric conditions in end-stage cancer patients was critically and rigorously assessed . The revHowever, we observed that the review did not include studies on classical or serotonergic hallucinogens/psychedelics such as lysergic acid diethylamide (LSD) and psilocybin in end-stage cancer. This is somewhat surprising, since these compounds were investigated for treating symptoms of depression and anxiety in patients suffering life-threatening diseases since the early 1960’s . A recenSince the four more recent trials reviewed in the above-mentioned systematic review (2011–2016) are all randomized, double-blind, placebo-controlled, cross-over clinical trials, only their data will be briefly discussed further –7. In thScore values, level of significance, statistical tests, and questionnaires used in each study are reported on Table n = 8) or 20  μg of LSD . M


Background: Intra-individual (IIV) of reaction time (RT), as the short-term fluctuations of RT-based performance, has been reported to be susceptible to cognitive ageing. The current study aimed to examine IIV of RT and its relationships with cognitive performance in cognitively normal senior adults. Methods: We evaluated 137 community-dwelling elderly (mean age: 72.41 ± 3.99) with a comprehensive neuropsychological battery and a RT-based test. Intraindividual coefficient of variation of reaction time (ICV-RT) was used to evaluate the IIV. Pearson’s correlation and hierarchical multiple regression analyses were employed to assess the relationships between IIV and the scores of cognitive function. Results: Advancing age was accompanied with declined cognitive function and increased IIV. ICV-RT was negatively correlated with the score of Montreal Cognitive Assessment Hong Kong version (HK MoCA) across three types of flanker. Hierarchical multiple regression showed that ICV-RT was a significant predictor of HK MoCA . Conclusion: Increased IIV is consistently associated with and contributed to the age-related decline of cognitive performance in senior adults. The utility of IIV in predicting further deterioration should be carefully postulated with prospective studies. Intra-individual variability (IIV), as a facet of within-person variation, has been regarded as a measure of short-term fluctuations in an individual’s performance . ThroughTherefore, it appears that the IIV of RT not just varies among the individuals with different age range, but also differs among the ones with different cognitive status. This phenomenon triggers another concern is whether the coupling change between age and IIV has a general effect on cognitive function or only linked to a specific cognitive domain? Besides, given the linkage between age and IIV reported in our recent work , we woulOne hundred and thirty-seven community-dwelling Chinese adults aged from 65–80 years were recruited from another cohort study that aims to establish a detailed characterization of cognitive and healthy profiles of Chinese senior adults. The eligible participants were scheduled for a 1.5-hour in-person interview at Chen Wai Wai Vivien foundation therapeutic physical mental exercise centre. During the on-site interview, the participants received a comprehensive evaluation , includiThe inclusion criteria of cognitively normal elderly were as follows: (1) aged 65 years and older; (2) no significant cognitive impairment: the ones with cognitive performance within 1.5 standard deviation (SD) of the age-normal reference see  derived A structured neuropsychological battery was used to assess the global cognition and major domains of cognition . CDR, AlCerebrovascular risks were evaluated by cumulative illness rating scale (CIRS)  with preAll the assessments were conducted with Chinese instructions. Ethical approval was obtained from the Joint Chinese University of Hong Kong-New territories East Cluster Clinical Research Ethics Committee. Written informed consent from all participants was obtained before the assessments.As described above, IIV represents the inconsistency of cognitive performance through repeated measurement. Attention network test (ANT) , as a weIn consideration of adjusting slowing processing speed in old age, intraindividual coefficient of variation of reaction time (ICV-RT) ,18 is usR2 value represented the increase in proportion of variance explained in step 1. Alpha was set as p < 0.05. The scores of accuracy and RT were calculated by E-Data Aid embedded in E-Prime 2.0 . The calculation of ICV-RT, Pearson’s correlation analysis and hierarchical multiple regression analysis was performed by IBM SPSS 20.As suggested by the developer of ANT , median r = 0.17, p = 0.042; TMT-B: r = −0.265, p = 0.002). As to IIV, a significant correlation was found between age and the average ICV-RT , indicating that adults with older age present greater short-term fluctuations on RT-based test. Moreover, prominent association was found between age and the ICV-RT under neutral flanker  instead of the difficult ones .With gender and education as covariates, significant correlations were found between age and cognitive function (CDR: r) became stronger when the types of flanker from lower cognitive demand  to higher cognitive demand . To further probe the associations between ICV-RT and cognitive function, hierarchical multiple regression analyses showed that the Δ2R change of average ICV-RT was significant  when regressing out the effect of age. In addition, Δ2R changes of the ICV-RT under three types of flanker were also significant , which indicates that increased short-term fluctuations contribute to the age-related decline of HK MoCA score.Using age, gender and education as covariates, a significant negative relationship was found between ICV-RT and HK MoCA . Besidesi.e., sample RT test with neutral flanker). In contrast, cognitive performance, such as HK MoCA, was negatively associated with the ICV-RT across different levels of cognitive demand. These findings suggest that the increased short-term fluctuations on RT-based performance might be a fundamental feature of cognitive ageing.The present study aimed to examine the relationships between intra-individual variability of RT and cognitive performance in community-dwelling cognitively normal senior adults. As expected, we observed several prominent associations between age, ICV-RT, and scores of cognitive function. In particular, advancing age was positively correlated with ICV-RT under the condition with lower cognitive demand  in RT-based test is likely be related to cognitive function , the absr seems spurious, further hierarchical multiple regression analyses partially reproduced the above trend with increased contributions  to ARCD. One possible explanation would be the implicit and explicit changes inside the ageing brain. Indeed, age-related changes of cognitive function occur gradually with the reduction of dopamine D2 receptor in the frontal lobe from the late 20s [However, as an unexpected result, there was a trend that the correlations between IIV and HK MoCA became stronger when the ICV-RT under the conditions with lower cognitive demand  to higher cognitive demand (congruent and incongruent). Although the corresponding change of absolute value of late 20s , but beclate 20s . Evidenclate 20s . The invlate 20s ,30. Fromlate 20s ,32.In the light of the preceding discussion, our results are aligned with the emerging evidence that cognitive ageing is accompanied by the dynamic changes, including increased IIV, slowing processing speed, and declined executive function . At thisDespite us providing an example of linking IIV to cognitive function, the results of the current study should be interpreted within its limitations. First, the classifications of cognitively normal senior adults were based on the scores of neurocognitive tests, not ascertained by neuroimaging and blood biomarkers. Second, this cross-sectional evaluation had limited power to infer any causative influence of findings. Third, all participants were from the Chinese community, which may not give an accurate reflection of the features of adults with various cultural backgrounds.


Self-healing materials have attracted much attention because that they possess the ability to increase the lifetime of materials and reduce the total cost of systems during the process of long-term use; incorporation of functional material enlarges their applications. Graphene, as a promising additive, has received great attention due to its large specific surface area, ultrahigh conductivity, strong antioxidant characteristics, thermal stability, high thermal conductivity, and good mechanical properties. In this brief review, graphene-containing polymer composites with self-healing properties are summarized including their preparations, self-healing conditions, properties, and applications. In addition, future perspectives of graphene/polymer composites are briefly discussed. Regenerative abilities allow creatures to repair damaged functions to prolong their life span. Researchers are inspired to design and prepare self-healing materials to increase the lifetime of materials and reduce the total cost of systems during the process of long-term use. Recently, great progress has been made in self-healing composite materials that possess the ability to restore their structure and functionality after damage. Early self-healing materials were focused on microcapsule or microtubule by release of healing agents to achieve repairing. However, the self-healing times of these methods are dependent on the amounts of healing agents in the microcapsule or microtubules . To addr2 carbon atoms, has attracted widespread attention in all kinds of research areas due to its large specific surface area, excellent electrical conductivity, thermal conductivity, and unique mechanical properties [Graphene, as a new type of two-dimensional planar monolayer of spoperties ,23,24,25operties ,28,29,30operties ,32,33,34In this review, the current advances in self-healing graphene/polymer composites have been summarized, including their preparation methods, self-healing conditions, properties and applications. Finally, the future prospects of the self-healing graphene/polymer composites are discussed.The simple mixing is the simplest and commonest method for preparing graphene or graphene derivative/polymer composites ,41,42,43Considering its easy agglomerate due to the strong π-π interactions, usually, graphene has been oxidized into graphene oxide (GO). Yan et al. fabricated chitosan/GO supramolecular hydrogels with self-healing properties . It was N,N-methylenebisacrylamide (MBA), and potassium persulfate, were added to the graphene dispersion in water and polymerized.In situ polymerization can be interpreted to mean that the monomer and graphene or graphene derivative were mixed firstly and subsequently polymerized by the addition of initiators ,56,57,58Taking advantage of this method, our group fabricated cationic PAM/GO self-healing hydrogels with tough, stretchable, compressive property . The GO During the in situ polymerization process, graphene can also be modified and participate in the polymerization, forming the covalent bond between graphene and polymers. For example, Karak et al. fabricated a tough self-healing elastomeric nanocomposite containing a castor oil-based hyperbranched polyurethane (PU) and an iron oxide nanoparticle decorated reduced graphene oxide (IORGO) nanohybrid . The IORSimilarly, Kim et al. synthesized a phenyl isocyanate modified GO and obtained the self-healing composites by condensation reaction of poly(tetramethylene glycol) and 4,4′-methylene diphenyl diisocyanate and phenyl isocyanate modified GO in the presence of phenylhydrazine  Figure b,c.The DA reaction and its retro-Diels-Alder (rDA) analogue is a promising route to introduce self-healing properties to polymeric systems, which can be performed under mild conditions without any catalyst or healing agent ,64,65,66The layer-by-layer (LBL) self-assembly technique is a versatile approach to fabricate multilayered nanostructural composites ,71,72,73Sun and coworkers reported an intrinsically healable, reduced graphene oxide (RGO)-reinforced polymer composite film via LBL assembly . RGO modApart from the aforementioned fabrication methods, there are other ways to fabricate self-healing graphene/polymer composites. Tang et al. reported conductive and self-healing nanocomposite hydrogels though a simple hydrothermal method . All theTo restore their original properties, graphene/polymer composites need to repair themselves autonomously or require external energy/stimuli such as mechanical force, light, heat, pH changes. In this section, different self-healing conditions of graphene/polymer composites were summarized.Heating is a common self-healing condition due to its easy operation. By heating, the mobility of polymer chains increases, thus facilitating the self-healing of graphene/polymer composites ,80,81,82Although heating is an easy way to repair damaged graphene/polymer composites, during heating other parts of devices are susceptive to heat, thus heating will cause interference of other parts of the devices and result in the deterioration of devices. Therefore, light radiation is an alternative way to repair the damaged composites. Graphene has good ability of photothermal energy transformation that makes the self-healing graphene/polymer composites usually show the same capacity . Zhang eN,N-dimethylacrylamide) hybrid hydrogel realized by NIR irradiation for only 2~3 min up to the strength recovery of ~96% [The near-infrared (NIR) irradiation has been suggested as a non-invasive, harmless and highly efficient skin-penetrating biomedical technique ,85. Tong of ~96% . GO acte of ~96% . When th of ~96% . The selN,N-dimethylacrylamide) chains on 3D graphene networks that exhibits good neural compatibility, high conductivity, low impedance and efficient NIR-triggered photothermal self-healing [Considering NIR as a non-invasive, harmless and highly efficient biomedical technique, it can be used in photothermal therapy. Wang et al. reported a hydrogel made by cross-linking poly. The polymer chains interdiffuse across the crack surface of the damaged fibrous membrane under 532 nm light irradiation, and recrystallize upon cooling after turning off the continuous-wave diode laser. The surface conductivity recovery by 91% and tensile strength of the membrane are still well maintained after multiple cutting-healing cycles .Graphene has an excellent microwaves absorption capability due to its large area conjugated π-structure ,90. UndeDeionized water or organic solvent is a practicable external stimulus to heal damage ,92,93,943+ hydrogel [3+ ions to the carboxyl groups on the PAA chains. Keeping the cut surfaces in contact and immersing them in FeCl3/HCl solution for a certain time gave rise to the self-healing process. After 15 h immersion, the healed hydrogel can bear a dumbbell of 5.5 kg. Importantly, the break position of the healed hydrogel after tensile test is not the healing position, proving the perfect connection of cut surfaces by Fe3+ ions  allow the polymer chains to diffuse and mix at room temperature, and be able to self-heal at room temperature without the need of any plasticizer, solvent, healing agents or external stimuli. Two cut pieces of samples were gently brought into contact and healed in less than 60 s. The obtained stress–strain curves were similar to that of the original uncut samples  based on GO and amine-terminated randomly branched oligomers . Both th samples . The HBN samples .3+ and catechol. No obvious cut line was seen and the healed sample can be stretched without fracturing by the tweezers.Kim et al. developed a mussel-mimetic nanocomposite hydrogel based on catechol-containing polyaspartamide and GO . Two pieApart from the aforementioned self-healing conditions, microcapsules are also utilized to heal the damaged composites, although this method cannot realize multiple healing in one damaged area. Gao et al. fabricated GO microcapsules (GOMCs) in Pickering emulsions containing linseed oil as the healing agent . The GO −3. The healed hydrogels also have favorable mechanical properties with a fracture strain of 2000% and a fracture strength of 153 kPa. GO played a role as the cross-link agent in the polyacrylamide network, which improved the tensile property . Primary GO sheets are well dispersed in the polymer matrix at low content (0.1 wt %). Sun et al. fabricated a covalent bonding GO/PU composite with significant mechanical reinforcement and thermal healable property. The Young’s modulus (21.95 ± 2.56 MPa) and fracture strain (449 ± 16%) increased twice and the fracture stress (8.01 ± 0.71 MPa) even increased nearly 4 times at a GO loading of only 0.1 wt %. The enhanced mechanical properties of the composites are ascribed to the good dispersion of GO and covalent linking based on DA chemistry . To imprco-acrylic acid) hybrid materials with shape memory behavior and self-healing ability [2/RGO nanocomposite fabricated by Karak et al. also possessed excellent shape memory behavior [Besides high mechanical properties, shape memory behavior is an attractive property for self-healing graphene/polymer composites due to their wide applications in machinery, electronic device, chemical industry, biology and other fields ,61,80,82behavior . As RGO For conductive graphene/polymer composites, the shape memory can be realized by electrical conductivity. When the content of conductive filler in a polymer matrix exceeds the percolation threshold, the conductive network can generate Joule heating. Therefore, the speed of the shape memory depends on the electrical conductivity of the filler. For instance, Mohammad and coworkers synthesized fast electroactive shape memory and self-healing PVA/graphene nanocomposites. The electrically triggered shape recovery experiments of the composite containing 3 and 4.5 wt % of graphene  were conducted under four different DC voltages  and the resulting recovery ratio as a function of recovery time is presented in +) transportation.Generally, a polymer is partially an insulator because the covalent bond of the polymer chain does not have free carries (electrons), on the other hand, as the polymer molecules pile together by van der Waals forces, the distances between the molecules are large, electrons overlap between the molecules are poor, so the free carries are very difficult to mobile in polymer . TherefoSupercapacitors are very common applications of conductive self-healing composite. For instance, Liu and Gao et al. assembled a stretchable and self-healable supercapacitor . The supFabrication of self-healing anticorrosive coatings has attracted attentions as it has the ability to extend the service life and prevent the substrate from corrosive attack. The self-healing coating on the surface of the material can repair the damaged surface automatically to protect the material ,109,110.One of the threats to human health is microbial contaminations or infections. Microbial fouling is the critical factor to degradation of polymeric self-healing materials. Therefore, antimicrobial activity is a fantastic property of self-healing composites. The nanocomposites prepared by Karak et al. exhibited good antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans because sulfur-containing compounds and polysulfanes are generally considered to be antimicrobial agents .N,N-dimethylacrylamide that can achieve a self-healing ability at 37 °C [The medical field also has great interest in self-healing materials. For example, Hu et al. fabricated a double network hydrogel based on β-CD functionalized graphene and at 37 °C . CamptotDue to the biocompatibility of DNA, the hydrogels can possess a variety of biological and environmental applications. Shi et al. reported GO/DNA self-healing hydrogels with high mechanical strength, excellent environmental stability, high dye-adsorption capacity and can be applied in tissue engineering, drug delivery, and removing organic pollutant . Self-healing hydrogels were proposed to be used as biomaterials because of the capability of spontaneously healing any injury. Lu et al. prepared a mussel-inspired conductive, self-adhesive, and self-healing tough hydrogel . The hydSelf-healing graphene/polymer composites are one of the most promising intelligent materials. The latest research progress in the preparation, properties and applications of self-healing graphene/polymer composites is reviewed and some of the composites are summarized in (1) Graphene, as a component of the self-healing composites, can play an active role in the self-healing process because of the photothermal energy transformation ability. In this case, graphene acts as an energy absorber to transform irradiation or sunlight to thermal energy rapidly and efficiently to promote the mutual diffusion of the polymer chains across the damaged interface, thus facilitating the self-healing process. On the other hand, graphene in the composites is only used as a reinforcing agent to enhance the mechanical strength. In this case, the self-healing process may be impeded because some interactions between graphene and polymers will limit the movement and diffusion of the polymer chains. In addition, the glass transition temperature of the composites may be changed after the addition of graphene, thus influencing the self-healing efficiency. Therefore, graphene as a reinforcing agent can improve the mechanical performance. However, the self-healing efficiency of the composite will be reduced. The mechanical properties and self-healing efficiency are two contradictory aspects. How to balance the two aspects to achieve graphene/polymer composites with both high mechanical strength and high self-healing efficiency is a challenge.(2) For intrinsically self-healing graphene-based materials, simple contacting without any external stimuli is considered to be most potential considering practical application. Therefore, exploring this kind of self-healing graphene-based composites is desired.(3) For electrical conductive graphene/polymer composites, the mechanical strength and the conductivity are two contradictory aspects. Increasing the graphene content will increase the conductivity of the composite, but excess graphene will reduce the mechanical strength. How to obtain high mechanical strength and high conductivity of the graphene/composites with self-healing properties is a challenge.(4) A lot of polymeric materials should be developed which exhibit self-healing properties. Also, it is highly challenging to endow the combined properties in a single material. The structural incompatibility among such types of polymers is one of the crucial reasons for this difficulty.(5) To improve the compatibility of polymer and graphene, graphene usually needs to be modified. However, modification of graphene will lose some inherent properties of graphene. Therefore, how to improve the compatibility of polymer and graphene and retain the inherent properties of graphene as much as possible in the composite is a challenge.In this review, we have summarized the recent progress of graphene-containing polymer composites with self-healing capability. The preparation methods, self-healing conditions, and properties and applications of the graphene/polymer composites have been briefly discussed. Finally, the further perspectives of the composites have been proposed. Intelligent materials and self-healing materials, specifically for graphene-containing composites, are still in the initial stage. There will be a great research space in the field. The progress will guide further development of the self-healing graphene/polymer composites.