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Background/Aims Actively engaging patient partners in the conduct of trials is crucial to ensure the studies answer genuine, patient-centered, unmet clinical needs, and to facilitate participant recruitment and retention. The aim of this article is to demonstrate the feasibility of patient engagement within a large pragmatic multicenter randomized controlled trial, specifically for the purposes of dissemination of study information/updates and to favorize recruitment and retention. Methods In the patient-centric, pragmatic ADAPTABLE randomized trial, transparent and timely dissemination of information on the study updates to the trial participants was undertaken to create meaningful engagement and to facilitate retention. A national panel of patient partners, the Adaptors, were directly involved in this information dissemination strategy, and study participants were engaged both nationally and locally to design recruitment methods iteratively during the conduct of the trial. All Adaptors had a lived experience with cardiovascular disease. Results Adaptors attended bi-weekly meetings facilitated by the director of the study’s patient-powered research network. They drafted and/or edited newsletters and ad hoc educational information written in a lay-friendly manner for study participants, which were regularly distributed to the ADAPTABLE community, in addition to online forums where participants could share their experience of their involvement in ADAPTABLE. To spur recruitment, a patient-driven initiative was to draft letters sharing their story, which were distributed by the local study teams. Patient partners thought that using patients’ voice to provide their perspectives on why they believed this project was important would be more engaging for prospective participants than traditional approaches. Conclusions ADAPTABLE’s experience has demonstrated the feasibility of engaging patients as partners in the conduct of a large-scale, multi-center, pragmatic randomized controlled trial. Future trials should embrace and iteratively improve this model by engaging patient partners as early as study protocol development and funding applications, and quantify its impact on the effectiveness and value of the trial.

Background and Purpose— Cardiac telemetry is a routine part of inpatient ischemic stroke/transient ischemic attack evaluation to assess for atrial fibrillation (AF). Yet, tools to assist stroke clinicians in the evaluation of the large quantities of telemetry data are limited. The investigators developed a new method to evaluate electrocardiographic signals, electrocardiomatrix, that was applied to stroke unit telemetry data to determine its feasibility, validity, and usefulness. Electrocardiomatrix displays telemetry data in a 3-dimensional matrix that allows for more accurate and less time consuming P-wave analysis. Methods— In this single-center, prospective, observational study conducted in a stroke unit, all telemetry data from ischemic stroke and transient ischemic attack patients were collected (April 2017–January 2018) for examination facilitated by electrocardiomatrix. AF>30 seconds was identified through review of electrocardiomatrix-generated matrices by a nonphysician researcher. Electrocardiomatrix results were compared with the clinical team’s medical record documentation of AF identified through telemetry. A study cardiologist reviewed the standard telemetry associated with all AF episodes identified by electrocardiomatrix and each case of disagreement. Results— Telemetry data (median 46 hours [interquartile range: 22–90]) were analyzed among 265 unique subjects (88% ischemic stroke). Electrocardiomatrix was successfully applied in 260 (98%) of cases. The positive predictive value of electrocardiomatrix compared with the clinical documentation was 86% overall and 100% among the subset with no prior history of AF. For the 5 false-positive and 5 false-negative cases, expert overview disagreed with the clinical documentation and confirmed the electrocardiomatrix-based diagnosis. Conclusions— The application of electrocardiomatrix to stroke unit-acquired telemetry data is feasible and appears to have superior accuracy compared with traditional monitor analysis by noncardiologists.

Sudden death is an important but underrecognized consequence of stroke. Acute stroke can disturb central control of autonomic function and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in the spontaneously hypertensive stroke-prone rat strain (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from nine SHRSP and eight Wistar-Kyoto (WKY) rats. RR interval was analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 h, whereas no mortality was observed in WKY rats. The functionality of both the brain and the heart were significantly altered in SHRSP compared with WKY rats after BCCAL. SHRSP, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of forebrain ischemia-induced sudden death. NEW & NOTEWORTHY This study demonstrates a marked surge of corticocardiac coupling in rats dying from focal cerebral ischemia, consistent with our earlier data in rats exposed to fatal asphyxia. Since the bidirectional electrical signal coupling (corticocardiac coherence) and communication (corticocardiac connectivity) between the brain and the heart are only identified in dying animals, they could be used as potential biomarkers to predict the risk of sudden death.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Introduction Obstructive sleep apnea (OSA) has been associated with bradycardic arrythmias and cases of transient heart block. Heart block occurring during sleep has been described in up to 10% of patients with obstructive sleep apnea, most commonly during stage R sleep and through a mechanism known as vagal activation. Stage R sleep is associated with desynchronization of respiratory and cardiovascular functions, and the excessive autonomic response (vagal activation) occurs due to the stronger stimulation of chemoreceptors and baroreceptors induced by hypoxemia, intrathoracic pressure swings, and hemodynamic alterations. Treatment of the underlying sleep-disordered breathing will typically treat the bradycardic arrythmia as well. Report of Cases: A 49-year-old male with a BMI of 30 kg/m , neck circumference of 16 inches, and obstructive sleep apnea presented to the sleep center to establish care for management of his preexisting OSA. He was previously diagnosed with moderate OSA in 2007 but had discontinued therapy shortly after due to Continuous Positive Airway Pressure (CPAP) intolerance. The patient complained of snoring, nocturia, and excessive daytime sleepiness (18/24 on Epworth Sleepiness Scale). During the split night study, the patient was noted to have 2:1 second degree heart block followed by a transient episode of complete heart block, manifested by 4 non-conducted p-waves. The patient remained asymptomatic throughout the night. Upon study completion, the patient denied any prior chest pain, presyncope, syncope, or medications that might cause heart block. Conclusion Bradyarrythmias can be seen in severe obstructive sleep apnea in the setting of excessive vagal stimulation through increased stimulation of chemoreceptors and baroreceptors. Treatment with PAP therapy can lead to prevention of heart block in 80-90% of these patients. Support (If Any)

Obstructive sleep apnea (OSA) commonly coexists with the metabolic syndrome, a condition for which behavioral changes are often prescribed. Whether OSA diminishes the cardiometabolic health benefits from lifestyle interventions remains unclear. We evaluated 278 consecutive metabolic syndrome participants enrolled in a 12‐week comprehensive lifestyle intervention program. The changes in blood pressure (BP), along with other metabolic health parameters, from baseline to follow‐up were compared between those with and without OSA. Mean age was 52.4 ± 10.9 years and 37% were male. At enrollment, mean body mass index (BMI) was 38.2 ± 7.7 kg/m(2). OSA was reported in 126 of 269 final participants (47%). At baseline, participants with reported OSA were more likely to be male, older, have a higher BMI, waist and neck size (all P

Background Atrial fibrillation (AFIB) and atrial flutter (AFL) are two common cardiac arrhythmias that predispose patients to serious medical conditions. There is a need to accurately detect these arrhythmias to prevent diseases and reduce mortality. Apart from accurately detecting these arrhythmias, it is also important to distinguish between AFIB and AFL due to differing clinical treatments. Methods In this study, we applied a new technology, the electrocardiomatrix (ECM) invented in our lab, in detecting AFIB and AFL in human patients. ECM converts 2D ECG signals into a 3D color matrix, which renders arrhythmia detection intuitive, fast, and accurate. Using ECM, we analyzed the ECG signals from the online MIT-BIH Atrial Fibrillation Database (PhysioNet), and compared our ECM-based results to manual annotations based on ECG by physicians. Results Results demonstrate that ECM and PhysioNet annotations of AFIB and AFL agree more than 99% of the time. The sensitivities of the ECM for AFIB and AFL detection were 99.2% and 98.0%, respectively, and the specificities of the ECM for AFIB and AFL were both at 99.8% and 99.8%. Conclusions This study demonstrates that ECM is a reliable method for accurate identification of AFIB and AFL.

Recurrent atrial fibrillation (AF) after successful cardioversion can be predicted by obstructive sleep apnea (OSA) diagnosed by polysomnography. However, it is not known whether the validated STOP-BANG questionnaire can predict AF recurrence after radiofrequency ablation (RFA). Our objective is to determine the prevalence of unrecognized OSA in patients with AF and its relation to freedom from AF after RFA.Validated surveys were administered to 247 consecutive AF patients following radiofrequency ablation from January to October 2011. OSA status was assessed at baseline RFA. Clinical follow up occurred at 3-6 month intervals.OSA had been previously diagnosed in 94/247 (38%). Among 153 patients without prior diagnosis of OSA, 121 (79%) had high risk STOP-BANG scores for OSA. Probability of maintaining sinus rhythm after RFA was similar among patients with known OSA (66/94, 70%) and high risk OSA scores (95/124, 77%) and higher than among patients with low risk OSA scores (29/32, 91%, P=0.03). Among patients without prior OSA, a high risk STOP-BANG score did predict recurrent AF (OR = 3.7, 95 % CI 1.4-11.4, P = 0.0005). Multivariate analysis showed a higher risk of atrial arrhythmia recurrence for non-paroxysmal AF patients (OR = 3.1, ± 95 % CI 1.4-7.1, P = 0.005).The majority of AF patients undergoing RFA have high risk OSA scores, suggesting that OSA is vastly underdiagnosed in this population. STOP-BANG independently predicted recurrent AF in patients without a prior diagnosis of OSA.

Noise has been identified as a major stressor in hospitals,1 ,2 with ambient noise frequently exceeding recommended levels set by the WHO3 and reportedly as high as alarm clocks.4 ,5 Although hospitals frequently attempt to reduce noise through traditional methods such as shielding the patient (eg, closing doors), moving equipment or altering staff behaviours, these approaches disrupt workflow and ignore the realities of sound generation required in modern hospitals, which potentially limits their impact on quality and patient safety. An unexplored method of reducing hospital noise borrowed from other industries is to use sound acoustic panels that diffuse noise rather than attempt to eliminate it.6 We performed a pilot study to determine whether strategically placed, sound acoustic panels applied in hospitals would acutely reduce noise in hallways adjacent to patient rooms. If true, this option could serve as an architectural design solution to enhance patient care and experience during hospitalisation. We conducted an observational, controlled study assessing sound levels on an active inpatient telemetry unit. Due to physical nature of sound acoustic panels, patients and staff were not blinded. Placement of panels and acoustic equipment met all institutional building management policies and national codes (figure 1). The inpatient telemetry unit is organised as two central parallel hallways with architecturally identical patient rooms on both sides. Walls and floors were hard surfaces designed for ease …

Background: Prevalence of obstructive sleep apnea (OSA) in hypertrophic cardiomyopathy (HCM) is estimated between 32% and 71%. Individuals with HCM and OSA have increased blood pressure, BMI, , ascending aorta size, left atrial size, left ventricular end diastolic diameter, E/e’ ratio, atrial fibrillation rates and NYHA functional class. It has been suggested that treatment of OSA can decrease the need for septal reduction. However, studies have found no effect of OSA on septal thickness or outflow gradient. It is not known how OSA affects exercise performance or cardiac remodeling assessed by MR. Genetic propensity toward OSA in HCM has not been reported. We propose that OSA predicts decrease exercise tolerance and that cardiac remodeling could be identified using MR. We sought to report on HCM genotype in OSA as well as compare our clinical and echo data with other investigators. Methods: Subjects were identified through our institution’s HCM database. They were surveyed using the STOP-BANG (SB) questionnaire, a validated questionnaire to identify individuals at high risk for OSA. We stratified patients into high risk (HR) and low risk (LR) groups, based on a cut point of greater than or equal to 3 on SB. Demographics and clinical characteristics were extracted from our database. Prevalence and means were compared between the two groups, using Chi-square and t-tests. Differences between the groups were adjusted for age, sex, and BMI using linear mixed models for continuous measures and logistic regression for dichotomous measures. Results: There were 206 respondents, of those 160 (78%) scored high risk for OSA, 60 of which had a history of polysomnogram (PSG) confirming OSA. Having a HR vs. LR SB was associated with a significantly greater likelihood of stroke, CHF hospitalization, NYHA functional class >2, reduced peak VO2, reduced anaerobic threshold and increased LA diameter. Adjusted comparisons for age, gender, and BMI showed that had significantly higher PAWP and LV mass index. Of those with a prior diagnosis of OSA we compared therapy compliant and non-compliant individuals and found they differed on LV mass index (HR=98.7 g/m2 vs. LR=62.0 g/m2, p=0.01). Conclusions: OSA occurs frequently in HCM and is associated with decreased exercise tolerance, worse hemodynamics, poor outcome as well as increased LV mass, which may be attenuated by therapy. OSA is an important and modifiable risk factor in HCM. Prospective evaluation utilizing PSG based diagnosis and positive pressure therapy is warranted.

Background —Plasminogen activator inhibitor type 1 (PAI-1) inhibits neointima formation after vascular injury. Hyperlipidemia modulates the expression of multiple genes, however, and the effects of PAI-1 on the arterial response to injury under hyperlipidemic conditions are unknown. The purpose of this study was to examine the impact of PAI-1 on intimal hyperplasia and other vascular changes that develop after arterial injury in apolipoprotein E–deficient (apoE −/− ) mice. Methods and Results —Ferric chloride injury of the midportion of the common carotid arteries of apoE −/− mice (n=22) induced formation of a neointima that contained smooth muscle cells, foam cells, neutral lipid, tissue factor, and von Willebrand factor. Interactions between vascular injury and apolipoprotein E deficiency were strongly synergistic; either stimulus alone was insufficient to induce significant neointima formation. Mean intima/media ratios were significantly greater ( P −/− , PAI-1 +/+ mice (5.6±1.8, n=12) than in apoE −/− , PAI-1 −/− mice (1.2±0.55, n=12), as were the percentages of bromodeoxyuridine-positive cells in the intima and media ( P −/− , PAI-1 +/+ mice than in apoE −/− , PAI-1 −/− mice. Conclusions —In atherosclerosis-prone mice, PAI-1 promotes neointima formation after oxidative vascular injury. The apparent hyperlipidemia-dependent effect of PAI-1 may be mediated by its capacity to inhibit the clearance of platelet-fibrin thrombi that can deliver growth factors to the blood vessel wall or be incorporated into developing vascular lesions. Alternatively, hyperlipidemia may alter the pattern of gene expression in the blood vessel wall to enhance potential effects of PAI-1 on antiproliferative processes, such as transforming growth factor-β activation and apoptosis.

Background: Radiographic contrast agents inhibit fibrinolysis, although by poorly defined path- ways. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis. Methods and Results: Diatrizoate (high osmolar ionic agent), ioxaglate (low osmolar ionic), and ioversol (nonionic) were studied in vitro. Diatrizoate inhibited clot lysis by 81.3 � 0.6% vs. control (p 0.3). Inhibition of fibrinolysis was not explained by the high osmolarities of contrast agents, by their iodine content, or by their effects on the amidolytic activities of t-PA, urokinase, or plasmin. However, plasminogen activation by t-PA, urokinase, or streptokinase was significantly inhibited by contrast agents. Diatrizoate, ioxaglate, and ioversol inhibited plasminogen binding to plasma clots by 51 � 4% (p < 0.001), 30.1 � 4% (p < 0.01), and 19.4 � 7% (p ¼ 0.07), respectively. Plasma clots formed in the presence of contrast agents were resistant to lysis by plasmin. Diatrizoate produced the most potent effect, inhibiting clot lysis by 40 � 5.7% (p < 0.03). Contrast agents did not inhibit plasminogen binding to fibrin or plasmin-mediated fibrinolysis if they were added after clot formation. Contrast agents altered clot turbidity, an index of fibrin structure, if present during clot formation, but not if added to preformed clots. Contrast agents did not affect plasminogen acti- vator inhibitor-1 or a2-antiplasmin function. Conclusions: Contrast agents inhibit clot lysis by inhibiting plasminogen activation and by disrupting interactions of plasminogen and plasmin with fibrin by altering fibrin structure. Significant variation in anti- fibrinolytic properties exists between different contrast agents. Abbreviated Abstract. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis. In both a purified clot lysis system and a plasma clot lysis system, diatrizoate, an ionic agent, produced the most potent inhibition of fibrino- lysis. Contrast agents did not inhibit the active sites of plasminogen activators or plasmin, but did inhibit plasminogen activation. Binding of plasminogen to fibrin and lysis of fibrin by plasmin were inhibited by contrast agents if they were present during clot forma- tion, but not if they were added after clot formation was complete. Contrast agents altered clot turbidity, an index of fibrin structure, if present during clot forma- tion, but not if added to preformed clots. Contrast agents did not affect plasminogen activator inhibitor- 1o ra2-antiplasmin function. The effects of contrast agents on fibrinolytic parameters were not explained by their high osmolarities. These results suggest that contrast agents inhibit clot lysis by inhibiting plasmi- nogen activation and by disrupting interactions of plasminogen and plasmin with fibrin by altering fibrin structure.

Background Patients are commonly provided tools in the hospital to overcome poor sleep. Whether education on use of sleep tools can impact health outcomes from a patient perspective is not known. Methods We recruited 120 adults admitted to a nonintensive care unit cardiac-monitored floor. All patients received a set of sleep-enhancing tools (eye mask, ear plugs, and a white noise machine) and were randomized to receive direct education on use of and benefit of these sleep-enhancing tools (intervention), or an equal amount of time was spent discussing general benefits of sleep (control). Measurement of several symptom domains was assessed daily by health outcome survey responses, and change from baseline was assessed for differences between groups. Inpatient opioid use and length of stay were also measured. Results Participants randomized to receive the education intervention had a significantly greater decrease in fatigue scores over the 3 days, compared with controls (5.30 ± 6.93 vs 1.81 ± 6.96, t = 2.32, P = .028). There was a trend toward improvements in multiple other sleep-related domains, including sleep disturbance, sleep-related impairment, physical functioning, pain severity, or pain interference (all P >.140). There was no difference in length of stay between intervention and control groups (7.40 ± 7.29 vs 7.71 ± 6.06 days, P = .996). The change in number of opioid equivalents taken did not differ use between the groups ( P = .688). Conclusion In a randomized trial of education in the use of sleep-enhancing tools while hospitalized, patient fatigue was significantly improved, whereas several other patient-reported outcomes showed a trend toward improvements. Implementation of this very low-cost approach to improving sleep and well-being could substantially improve the patient care experience.

Date Presented 4/9/2016 Occupational therapy sleep tool intervention demonstrates a positive effect on pain reduction associated with sleep deprivation. To improve patient outcomes, hospital-based occupational therapist roles should routinely include sleep education as part of their domain. Primary Author and Speaker: Kristen Clore Additional Authors and Speakers: Mary Whitehouse Barber, Melissa Johnson, Christelle David Contributing Authors: Steven Heidt, Julia Meireles, Brittany Gappy, Bridget Higgy, Zainab Rasheed, Ryan Scott, Giancarlo Vanini, Peter Farrehi

Date Presented 4/8/2016 Simple sleep-enhancing education can significantly improve perceptions of sleep quality, wake disturbance, and fatigue in hospitalized adults. Occupational therapists have the opportunity to implement this education in their daily roles. Primary Author and Speaker: Steven Heidt Contributing Authors: J. Ryan Scott, Kristen Clore, Christelle David, Melissa Johnson, Brittany Gappy, Bridget Higgins, Zainab Rasheed, Julia Meireles, Peter Farrehi

The number of patients with implantable electronic devices (IEDs) is growing as indications for a myriad of cardiac and neurological disorders that cannot be managed using medication alone expand. 1 These devices include gastric and cardiac pacemakers, implantable cardioverter defibrillators, cochlear implants, and a range of stimulators of the deep brain, vagal nerve, sacral nerve, phrenic nerve, spinal cord, and bone. Encountering patients with an IED who present for office-based procedures is becoming increasingly common. Electromagnetic interference (EMI) during routine procedures has been reported to be associated with inappropriate functioning of IEDs. 2 Adverse effects of performing electrosurgery on patients with IEDs pose a patient safety risk. Medical and manufacturer reports have primarily focused on larger electrosurgical equipment used in hospitals and their effect on IEDs. Our purpose was to provide a clinical review of commonly encountered IEDs, their clinical indications, potential interference with officebased electrosurgical equipment, and recommendations to prevent complications and injury.

Background —Platelet-rich arterial thrombi are resistant to lysis by plasminogen activators. However, the mechanisms underlying thrombolysis resistance are poorly defined. Plasminogen activator inhibitor-1 (PAI-1), which is present in plasma, platelets, and vascular endothelium, may be an important determinant of the resistance of arterial thrombi to lysis. However, in vitro studies examining the regulation of platelet-rich clot lysis by PAI-1 have yielded inconsistent results. Methods and Results —We developed a murine arterial injury model and applied it to wild-type ( PAI-1 +/+) and PAI-1–deficient ( PAI-1 −/−) animals. FeCl 3 was used to induce carotid artery thrombosis. Thrombi consisted predominantly of dense platelet aggregates, consistent with the histology of thrombi in large-animal arterial injury models and human acute coronary syndromes. To examine the role of PAI-1 in regulating endogenous clearance of platelet-rich arterial thrombi, thrombi were induced in 22 PAI-1 +/+ mice 14 PAI-1 −/− mice. Twenty-four hours later, the amount of residual thrombus was determined by histological analysis of multiple transverse sections of each artery. Residual thrombus was detected in 55 of 85 sections (64.7%) obtained from PAI-1 +/+ mice compared with 19 of 56 sections (33.9%) from PAI-1 −/− mice ( P =.009). Computer-assisted planimetry analysis revealed that mean thrombus cross-sectional area was 0.033±0.027 mm 2 in PAI-1 +/+ mice versus 0.016±0.015 mm 2 in PAI-1 −/− mice ( P =.048). Conclusions —PAI-1 is an important determinant of thrombolysis at sites of arterial injury. Application of this model to other genetically altered mice should prove useful for studying the molecular determinants of arterial thrombosis and thrombolysis.