State of pediatric liver transplantation in the United States and achieving zero wait list mortality with ideal outcomes: A statement from the Starzl Network for Excellence in Pediatric Transplant Surgeon's Working Group.

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Perception and reaction of Nanyang Technological University (NTU) researchers to different forms of research integrity education modality.

BACKGROUND: Research and academic institutions use various delivery channels to deliver Research Integrity (RI) education in their communities. Yet there is no consensus on the best delivery method and the effectiveness of these channels in inculcating a positive RI culture varies across institutions. Hence, this study aimed to understand the preferences of the research community in Nanyang Technological University (NTU), Singapore. METHODS: An online survey was conducted on NTU research community to understand their experience with, and preference for each RI education mode offered in NTU. The RI education modes surveyed in the general ranking question are Data Management Plan (DMP) workshops, Epigeum e-Learning, Compass e-newsletter (email), and NTU policy on Research Integrity and Responsible Conduct of Research. There were 242 responses, comprising 50% research students, 32.2% research staff and 17.8% faculty members. Non-parametric statistical techniques were used to analyse preferences across different RI education modes and within sub-groups (i.e., fields, age, native language, roles in research community). RESULTS: More than 92% of respondents subscribed to the importance of RI education, but with different preferences for education modes. With respect to RI education in NTU, Compass e-newsletters were ranked the lowest (p < 0.05). Most felt that they were too wordy and unengaging, making it difficult to absorb information. Similarly, Epigeum e-Learning (p < 0.05) and 'policy' (p < 0.05) were found to be too lengthy in presentation. The compulsory NTU RI education modes (Epigeum e-learning and 'policy') enjoyed higher participation rates of 70-80% compared with 32-37% for the self-regulated modes (DMP workshop and e-newsletter). This suggests that regulatory mechanisms are still necessary to promote participation in RI education, and thus, core RI education content should be made compulsory in research/academic institutions. Although Epigeum is a compulsory course, some may not have participated in the programme due to technical issues or they might have forgotten to participate in the programme within the permissible timeframe. For all four RI education modes in NTU, the lack of awareness was among the top cited reasons for not participating. CONCLUSIONS: Most NTU researchers perceived RI education positively although they may have reservations for some approaches. Conversely, e-Learning is favored over all the other modes except for the mode of Policy. Findings from this study are useful for improving the design of RI education strategies to be more appealing to the research community by enhancing user experience in terms of user-friendliness, relevance to specialisation, providing concise information and better presentation of materials For institutions with similar modes of RI education as NTU, these results may be relevant in improving participation rates and presentation of RI education modes, such as the use of infographics and more concise information.

Is lower dose of intramuscular dexamethasone injection beneficial in reducing neonatal respiratory morbidity for elective caesarean section deliveries at 37 to 38 weeks? An observational study.

INTRODUCTION: The use of intramuscular (IM) dexamethasone injections before an elective caesarean delivery at term has been shown in multiple randomized controlled trials to reduce the rates of transient tachypnoea of the newborn, and admission to neonatal care. Recent studies have suggested that a complete course of IM steroids can be associated with long term harmful consequences to the infants born, and there have been studies suggesting that a lower dose of IM corticosteroids can be beneficial. Therefore, we aim to establish if halving the dose of dexamethasone to 12mg can demonstrate any benefit for term elective caesarean section deliveries whilst minimizing foetal exposure. METHODS: An observational controlled study comparing neonatal respiratory morbidities before and after the single dose 12mg dexamethasone was implemented in our obstetrics and gynaecology centre for term elective caesarean section deliveries. We included singleton pregnancies from 37+0 to 38+6 weeks undergoing elective caesarean section into our study. A total of 674 patients fulfilled the inclusion criteria and were recruited. We compared the rates and duration of admission to neonatal intensive care unit, the need for mechanical ventilation and the rate of transient tachypnoea of the newborn in the first half of 2019 without IM dexamethasone injections against the second half of the year when a single dose IM dexamethasone was given. RESULTS: IM dexamethasone injection did not show any significant benefit with regards to reducing the admission to neonatal care (OR 0.97, p- value 0.69), admission to neonatal intensive care unit (OR 0.91, p- value 0.80), the need for mechanical ventilation (OR 0.98, p- value 0.95), and the incidence of transient tachypnoea of the newborn (OR1.01, p- value 0.96). There was also no significant difference for the duration of admission in the neonatal intensive care unit for both groups (p- value 0.17). CONCLUSIONS: This study showed that there was no significant benefit gained from the lower dose antenatal corticosteroids for term elective caesarean section deliveries and considering that there have been long term harmful consequences demonstrated from the higher dose of antenatal corticosteroids at term, this practice should therefore be discontinued until a larger study is done to refute these findings. The use of such dexamethasone should only be a viable option in a research setting.

Pre- and Post-operative determinants of transplantation-free survival after Fontan. The Australia and New Zealand experience.

BACKGROUND: This review identifies the predictors of late mortality and heart transplantation that remain relevant in the contemporary population of patients with a Fontan circulation, focusing on the potential impact of post-Fontan morbidities on the late outlook of these patients. METHODS AND RESULTS: A total of 1561 patients who had survived the Fontan operation in Australia or New Zealand from 1975 to 2018 were included in this review. Over a median duration of 11.4 years, there was a total of 117 deaths (7%) and 32 heart transplantations (2%). Freedom from death and heart transplantation at 10, 20 and 35 years post Fontan surgery were 94% (95% CI 93-95%), 87% (95 %CI 85-90%) and 66% (95 %CI 57-78%) respectively. Being male, having an atriopulmonary Fontan, pre-Fontan atrioventricular valve intervention, or prolonged pleural effusions post Fontan were predictive of late death or heart transplantation. However, time-dependent variables such as the development of atrial arrhythmia, protein/losing enteropathy or late ventricular dysfunction were stronger predictors of the same outcome. Patients who developed a time-dependent risk factor had a freedom from death and heart transplantation rate of 54% (95 %CI 43-66) at 15 years and 44% (95 %CI 33-57) at 25 years post Fontan. However, 95% (95 %CI 91-99) of patients without any of the identified risk factors were free from death or heart transplantation rate at 25 years post Fontan. CONCLUSION: In conclusion, the occurrence of post-operative complications such as PLE, arrhythmia and ventricular dysfunction will likely precede the late demise of these patients.

Cardiopulmonary exercise test indices of respiratory buffering before and after aerobic exercise training in women with pulmonary hypertension: Differentiation by magnitudes of change in six-minute walk test performance.

While aerobic exercise training (AET) has generally been shown to improve 6-min walk test (6MWT) distance (6MWD) in patients with pulmonary hypertension (PH), a substantial number of patients appear to adapt differently, with minimal or even negative changes in 6MWT distance being reported. PURPOSE: To compare post-aerobic exercise training adaptations in cardiorespiratory functional capacity across three groups of patients with PH: those with high (HI), low (LI) and negative (NEG) post-training increases in 6MWD. METHODS: Participants were 25 females (age 54 ± 11 years; BMI 31 ± 7 kg/m2) who completed a vigorous, 10-week, thrice weekly, supervised treadmill walking exercise program. Cardiopulmonary exercise tests (CPET) and 6MWT were completed before and after training. Ten of the 25 participants were classified as HI (range = 47-143 m), 11 were classified as LI (range = 4-37 m) and 4 were classified as NEG (range = -17 to -53 m). RESULTS: Peak CPET duration, WR and time to anaerobic threshold (AT) were significantly higher (p < 0.05) after training in both the LI and HI groups but not in the NEG group. There was a significant improvement in VE/VCO2 (p = 0.042), PETCO2 (p = 0.011) and TV (p = 0.050) in the HI group after training, but not in the NEG or LI group. CONCLUSION: These findings suggest that sustained ventilatory inefficiency and restricted respiratory buffering may mediate exercise intolerance and impede the ability to adapt to exercise training in some patients with PH.

Microring resonator-assisted Fourier transform spectrometer with enhanced resolution and large bandwidth in single chip solution.

Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The "Author contributions" was amended to reflect the authorship changes. It previously read 'Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.' The correct version states 'B.L., K. W., P.H.Y.' instead of 'B.L., P.H.Y.' and 'S.H.L.' in place of 'L.S.H.'This has been corrected in both the PDF and HTML versions of the Article.

The impact of morphological characteristics on late outcomes in patients born with hypoplastic left heart syndrome†.

OBJECTIVES: Patients with hypoplastic left heart syndrome are at high risk of late adverse events after Fontan completion, but it is unclear whether their morphological characteristics influence these outcomes. METHODS: Retrospective review of the data from the Australian and New Zealand Fontan Registry identified 185 patients with hypoplastic left heart syndrome who survived to hospital discharge after Fontan completion. Their outcomes were reviewed to identify predictors of adverse events with a particular focus on the impact of morphological characteristics. All available echocardiographic parameters were collected, and the hypoplasia of the left ventricle was subjectively considered to be mild, moderate or severe. RESULTS: The mean follow-up after the Fontan procedure was 6.4 ± 4.7 years. The median age at Fontan procedure was 4.41 years, 95% (176/185) of patients underwent an extracardiac conduit Fontan procedure and 71% (132/185) of those were fenestrated. At 15 years after Fontan, freedom from death and cardiac transplantation was 90% [95% confidence interval (CI) 85-97], freedom from Fontan failure was 78% (95% CI 70-87) and freedom from adverse events was 32% (95% CI 22-46). Morphological parameters did not influence transplant-free survival or Fontan failure. Independent risk factors predicting higher incidence of adverse events included aortic atresia (P = 0.003). CONCLUSIONS: The long-term survival of Fontan survivors with hypoplastic left heart syndrome is excellent and appears comparable to that of the general Fontan population. However, intrinsic morphological characteristics may continue to burden patients with late morbidity.

Pacemakers are associated with a higher risk of late death and transplantation in the Fontan population.

BACKGROUND: The need for permanent pacing has been identified as a predictor of poor outcomes in the late survivors of Fontan surgery. However, it is not clear if the need for a pacemaker is a surrogate marker of a declining Fontan state, or if pacing is deleterious to the Fontan circulation. OBJECTIVES: We sought to compare the long-term outcomes of propensity-matched Fontan patients with and without a permanent pacemaker. METHODS: Patients who have survived Fontan completion with a documented history of cardiac arrhythmia were identified from the Australia and New Zealand Fontan Registry. Pacemaker insertion details, cardiac function and electrophysiological data were obtained for the patients with a permanent pacemaker. Survival analysis was performed with propensity score matching to compare late survival and outcomes in patients with versus without a pacemaker. RESULTS: There was a total of 310 patients with a history of cardiac arrhythmia, of which 126 (41%) had a permanent pacemaker. After propensity-score matching, 99 pairs were generated (n = 198). Patients with a permanent pacemaker had a higher risk of death (HR 3.32 95% CI 1.60-6.90, p = 0.001) and death or transplantation (HR 3.55 95% CI 1.87-6.73, p < 0.001). Patients who were only paced atrially were not at a significantly increased risk of death or transplantation. However, patients who were ventricular paced >50% of the time were much more likely to encounter late death or transplantation (HR 3.82 95% CI 1.64-8.95, p = 0.002). CONCLUSIONS: Having a permanent pacemaker and needing ventricular pacing is likely associated with an increased risk of death and transplantation in patients with a Fontan circulation.

Improved Survival After the Ross Procedure Compared With Mechanical Aortic Valve Replacement.

BACKGROUND: It is unclear whether the Ross procedure offers superior survival compared with mechanical aortic valve replacement (AVR). OBJECTIVES: This study evaluated experience and compared long-term survival between the Ross procedure and mechanical AVR. METHODS: Between 1992 and 2016, a total of 392 Ross procedures were performed. These were compared with 1,928 isolated mechanical AVRs performed during the same time period as identified using the University of Melbourne and Australia and New Zealand Society of Cardiac and Thoracic Surgeons' Cardiac Surgery Databases. Only patients between 18 and 65 years of age were included. Propensity-score matching was performed for risk adjustment. RESULTS: Ross procedure patients were younger, and had fewer cardiovascular risk factors. The Ross procedure was associated with longer cardiopulmonary bypass and aortic cross-clamp times. Thirty-day mortality was similar (Ross, 0.3%; mechanical, 0.8%; p = 0.5). Ross procedure patients experienced superior unadjusted long-term survival at 20 years (Ross, 95%; mechanical, 68%; p < 0.001). Multivariable analysis showed the Ross procedure to be associated with a reduced risk of late mortality (hazard ratio: 0.34; 95% confidence internal: 0.17 to 0.67; p < 0.001). Among 275 propensity-score matched pairs, Ross procedure patients had superior survival at 20 years (Ross, 94%; mechanical, 84%; p = 0.018). CONCLUSIONS: In this Australian, propensity-score matched study, the Ross procedure was associated with better long-term survival compared with mechanical AVR. In younger patients, with a long life expectancy, the Ross procedure should be considered in centers with sufficient expertise.

The Ross procedure in adults presenting with bicuspid aortic valve and pure aortic regurgitation: 85% freedom from reoperation at 20 years.

OBJECTIVES: The Ross procedure has demonstrated excellent results when performed in patients with aortic stenosis or mixed aortic valve disease [aortic stenosis and aortic regurgitation (AR)]. However, due to its reported risk of late reoperation, it is not recommended under current guidelines for patients presenting with bicuspid aortic valve and pure AR. We have analysed our own results in light of this recommendation. METHODS: Between 1993 and 2016, 129 consecutive patients with a mean age of 34.7 ± 10.6 years (range 16-64 years) presented with bicuspid aortic valve and pure AR and underwent the Ross procedure. Patients were reviewed annually and had 2nd yearly transthoracic echocardiograms during follow-up. The unit had a liberal reoperation policy where reoperation was performed if patients developed recurrent moderate or greater AR during follow-up. RESULTS: There was 1 inpatient death, and 3 late deaths over a mean follow-up duration of 9.6 ± 6.8 years. Late survival at 10 and 20 years post-surgery were 99% [95% confidence interval (CI) 94-100] and 95% (95% CI 85-99), respectively. Eleven patients underwent redo aortic valve replacement (AVR) and 4 patients had redo pulmonary valve replacement. Freedom from reoperation for AVR and more-than-mild AR at 10 and 20 years post-surgery were 89% (95% CI 81-94) and 85% (95% CI 74-92), respectively. Having longer aortic cross-clamp (hazard ratio 1.03, 95% CI 1.00-1.06; P = 0.05) and cardiopulmonary bypass times (hazard ratio 1.02, 95% CI 1.00-1.05; P = 0.05), and having a larger preoperative sinotubular junction diameter (hazard ratio 1.15, 95% CI 1.03-1.30; P = 0.02) were significant predictors of having redo AVR or significant AR at follow-up. CONCLUSIONS: With a 20-year freedom from redo AVR and greater-than-mild residual AR of 85%, the utilization of the Ross procedure in bicuspid aortic valve patients with pure AR should be considered.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.

High-resolution and multi-range particle separation by microscopic vibration in an optofluidic chip.

An optofluidic chip is demonstrated in experiments for high-resolution and multi-range particle separation through the optically-induced microscopic vibration effect, where nanoparticles are trapped in loosely overdamped optical potential wells created with combined optical and fluidic constraints. It is the first demonstration of separating single nanoparticles with diameters ranging from 60 to 100 nm with a resolution of 10 nm. Nanoparticles vibrate with an amplitude of 3-7 µm in the loosely overdamped potential wells in the microchannel. The proposed optofluidic device is capable of high-resolution particle separation at both nanoscale and microscale without reconfiguring the device. The separation of bacteria from other larger cells is accomplished using the same chip and operation conditions. The unique trapping mechanism and the superb performance in high-resolution and multi-range particle separation of the proposed optofluidic chip promise great potential for a diverse range of biomedical applications.

Ventricular assist device support in patients with single ventricles: the Melbourne experience.

OBJECTIVES: The capacity and limitations of ventricular assist device (VAD) support in single-ventricle physiology remains poorly understood. We aimed to review our experience in the use of VAD support in the single-ventricle circulation to determine its feasibility in this population. METHODS: We reviewed our experience with VAD support in patients with single ventricles over the past 25 years. Fifty-seven patients received 64 runs of VAD support between 1990 and 2015 at a median age of 13 days [interquartile range (IQR) 4.1-99.4 days], of which 55 were supported for post-cardiotomy failure. The majority of patients received short-term VAD support, while 4 patients were either directly supported (1) or transitioned onto the Berlin Heart EXCOR (3). RESULTS: The median duration of support was 3.5 days (IQR 2.8-5.2 days). Twelve patients suffered significant neurological complications, and thromboembolic events occurred in 8 patients. Twenty-nine of the 55 patients were successfully weaned off support (53%). There were 37 inpatient deaths, with a survival-to-hospital discharge rate of 33% (18 of 55). Of the 4 patients supported after early Fontan failure, 3 died. Having a higher mean arterial blood pressure on initiation of VAD support was the only significant predictor of death (hazards ratio 1.08; 95% confidence interval 1.03-1.14; P = 0.002). Patients who required a second run of support had higher hospital mortality (83% vs 63%; P = 0.84). Of the hospital survivors, 12 patients (63%) remain alive without heart transplantation at median 7.2 years (IQR 3.5-14.0) post VAD support. CONCLUSIONS: VAD support in patients with a single ventricle has a high hospital mortality, with 1 of 3 patients surviving to discharge. Systemic VAD support is likely futile in the setting of early Fontan failure or when re-initiation of support is required.

Correction: Optofluidic lens with low spherical and low field curvature aberrations.

Correction for 'Optofluidic lens with low spherical and low field curvature aberrations' by H. T. Zhao et al., Lab Chip, 2016, 16, 1617-1624.

Optofluidic lens with low spherical and low field curvature aberrations.

This paper reports an optofluidic lens with low spherical and low field curvature aberrations through the desired refractive index profile by precisely controlling the mixing between ethylene glycol and deionized water in an optofluidic chip. The experimental results demonstrate that the spherical aberration is reduced to 19.5 µm and the full width at half maximum of the focal point is 7.8 µm with a wide divergence angle of 35 degrees. In addition, the optofluidic lens can focus light at different off-axis positions on the focal plane with Δx' < 6.8 µm and at opposite transverse positions with |Δy - Δy'| < 5.7 µm. This is the first demonstration of a special optofluidic lens that significantly reduces both the spherical and field curvature aberrations, which enhances the focusing power and facilitates multiple light source illumination using a single lens. It is anticipated to have high potential for applications such as on-chip light manipulation, sample illumination and multiplexed detection.

Cell refractive index for cell biology and disease diagnosis: past, present and future.

Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.

A Cholesterol-Dependent Endocytic Mechanism Generates Midbody Tubules During Cytokinesis.

Cytokinesis is the final stage of cell division and produces two independent daughter cells. Vesicles derived from internal membrane stores, such as the Golgi, lysosomes, and early and recycling endosomes accumulate at the intracellular bridge (ICB) during cytokinesis. Here, we use electron tomography to show that many ICB vesicles are not independent but connected, forming a newly described ICB vesicular structure - narrow tubules that are often branched. These 'midbody tubules' labelled with horseradish peroxidase (HRP) within 10 min after addition to the surrounding medium demonstrating that they are derived from endocytosis. HRP-labelled vesicles and tubules were observed at the rim of the ICB after only 1 min, suggesting that midbody tubules are likely to be generated by local endocytosis occurring at the ICB rim. Indeed, at least one tubule was open to the extracellular space, indicative of a local origin within the ICB. Inhibition of cholesterol-dependent endocytosis by exposure to methyl-ß-cyclodextrin and filipin reduced formation of HRP-labelled midbody tubules, and induced multinucleation following ICB formation. In contrast, dynamin inhibitors, which block clathrin-mediated endocytosis, induced multinucleation but had no effect on the formation of HRP-labelled midbody tubules. Therefore, our data reveal the existence of a cholesterol-dependent endocytic pathway occurring locally at the ICB, which contributes to the accumulation of vesicles and tubules that contribute to the completion of cytokinesis.