Bronchoscopy for Chronic Unexplained Cough: Use of Biopsies and Cultures Increase Diagnostic Yield Background: Prior studies assessing the diagnostic utility of bronchoscopy for chronic unexplained cough have focused primarily on identifying endobronchial anomalies to determine chronic cough etiology. On the basis of our institutional experience, expanding bronchoscopy to include cultures and biopsies can considerably increase its diagnostic yield for identifying the etiology of chronic unexplained cough. Materials and Methods: This retrospective review analyzed bronchoscopies conducted in our institution between 2013 and 2017. Eligibility criteria were bronchoscopies conducted for chronic unexplained cough for which no etiology had been identified before the bronchoscopy. Microbiology, pathology, and cytology results from bronchoscopy were reviewed to identify the etiology of the cough. Results: Over the study period, 169 bronchoscopies met the eligibility criteria. The average patient age at bronchoscopy was 59.7±14.8 years; 61% were female individuals. Direct visualization identified anatomic etiologies in 48 (28%) patients, most commonly tracheobronchomalacia, and less common conditions, such as tracheobronchopathia osteochondroplastica. Microbiology cultures were positive in 33 (20%) patients, principally Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and nontuberculosis mycobacterium. Pathology results from endobronchial biopsies identified respiratory conditions associated with cough, primarily eosinophilic bronchitis (n=15), as well as neurofibromatosis (n=1) and amyloidosis (n=1). Cytology results did not reveal alternate diagnoses not previously identified. Conclusion: Inclusion of bronchial washings and endobronchial biopsies during bronchoscopy for chronic unexplained cough increased diagnostic yield from 28%, attributable to directly visualized anatomic etiologies, to 41%. The addition of microbiology cultures and pathology analysis significantly increased the diagnostic yield of bronchoscopy in identifying the potential etiology of chronic heretofore unexplained cough. Disclosure: There is no conflict of interest or other disclosures. Reprints: Moshe Heching, MD, Rabin Medical Center, 39 Ze’ev Jabotinsky Road, Petah Tikva, 4941492 Israel (e-mail: moshehe@clalit.org.il). Received January 9, 2019 Accepted September 20, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ultrasound Evaluation of Hemidiaphragm Function Following Thoracentesis: A Study on Mechanisms of Dyspnea Related to Pleural Effusion Introduction: Dyspnea is the major symptom caused by pleural effusion. The pathophysiological pathways leading to dyspnea are poorly understood. Dysfunction of respiratory mechanics may be a factor. We aimed to study the change in diaphragmatic function following thoracentesis. Methods: Patients undergoing thoracentesis at a highly specialized pleural center, underwent ultrasound evaluation of hemidiaphragm movement, before and after thoracentesis was performed. The change was compared to the reduction of dyspnea measured at the modified Borg scale. Results: Thirty-two patients were included. Dyspnea was reduced from 5.01 [95% confidence interval (CI): 4.12-6.04] to 2.6 (95% CI: 1.87-3.4, P<0.0001). Low hemidiaphragmatic movement before thoracentesis on the side of pleural effusion was improved by 17.4 cm2 (95% CI: 13.04-21.08), equalizing movement to the side without pleural effusion. On average, 1283 mL (SD: 469) fluid was drained. Multiple linear regression analysis showed that prethoracentesis ultrasound evaluation of hemidiaphragmatic function was correlated with successful thoracentesis. Conclusion: Hemidiaphragm function is reduced on the side of pleural effusion, and thoracentesis restores function. Improvement in diaphragm movement is related to a reduction in dyspnea. Some of the data were presented as a poster at the European Respiratory Society Congress in 2019. S.H.S.: concepted hypothesis, generated study design, and was involved in the collection, analysis, and interpretation of data and writing of manuscript. G.M. and P.C.: contributed to the study design, interpretation of data, and writing of manuscript. S.L., A.V., and F.Q.: contributed to the acquisition of data, interpretation of data, and writing of manuscript. Disclosure: There is no conflict of interest or other disclosures. Reprints: Søren H. Skaarup, MD, Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Palle Juul Jensens Boulevard, Aarhus N 8200, Denmark (e-mail: soeska@rm.dk). Received June 1, 2019 Accepted September 6, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Jet Ventilation Decreases Target Motion and Increases Yield of ENB Especially in Lesions With Negative Bronchus Sign Background: Electromagnetic navigational bronchoscopy (ENB) is used to obtain peripheral lung tissue samples for evaluation and staging of central and peripheral lung lesions. Jet ventilation delivers and maintains a sustained airway pressure at high frequency, chest wall and diaphragmatic movement is drastically reduced compared with traditional ventilation. The current study looks to examine the effectiveness of tissue sampling (diagnostic yield) while using jet ventilation on target-lesion movement when compared with traditional ventilation. Methods: A total of 36 patients received total intravenous anesthesia with both jet and traditional ventilation during ENB procedure where sensor to lesion displacement was recorded. When planning the ENB procedure, the presence or absence of a viable airway to the lesion was recorded. Sensor to lesion movement was recorded and compared for significance using χ2 and t tests, utilizing stringent P-values. Results: Overall patients with an airway to the lesion (n=23) had a higher proportion of successful diagnostic biopsies, 83% compared with those patients that lacked an airway to the lesion (n=13) 70% proportion of successful diagnostic biopsies. When using jet ventilation, the chance of nonzero displacement was 8.3% (0.14 mm), regardless of the presence of an airway. Compared with traditional ventilation, the chance of a nonzero displacement between the sensor and target-lesion was 83% (6.4 mm), independent of airway presence to the lesions. Conclusion: In patients without an airway, jet ventilation significantly decreased target displacement when compared with traditional ventilation (2 vs. 17 mm). In patients with direct airway to the lesion, jet ventilation did not significantly decrease target displacement when compared with the traditional approach. Disclosure: There is no conflict of interest or other disclosures. Reprints: Tracey N. Webb, BS, Department of Psychology, Emory University, 2691 Mercedes Drive N.E., Atlanta, GA 30345 (e-mail: webb.tnicole@gmail.com). Received December 18, 2018 Accepted May 3, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Prospective Outcome Assessment After Bronchoscopic Interventions for Malignant Central Airway Obstruction Background: A systematic assessment of comprehensive clinical outcomes after various therapeutic procedures for malignant central airway obstruction (CAO) is lacking. Methods: Patients with symptomatic malignant CAO undergoing various therapeutic bronchoscopy procedures were assessed for symptomatic and functional improvement using the Speiser Score, spirometry, 6-minute walk distance (6MWD), and St. George Respiratory Questionnaire (SGRQ) up to 3 months after the procedures. Results: A total of 83 intervention procedures were performed in 65 patients, comprising 43 (66.2%) male individuals [overall mean age, 52.4; SD, 15.4 y]. The majority of these (92.3%) was done using rigid bronchoscope under general anesthesia. Airway stenting was the most common intervention performed (56.6%), followed by mechanical debulking (26.5%), cryodebulking (6%), electrosurgical removal (4.8%), balloon dilatation (3.6%), and laser ablation (2.4%). A total of 15 complications (18.1%) were noted. Of these, 8 (53.3%) were early complications and 7 (46.7%) were late complications. Early complications included airway bleeding, hypoxia, vocal cord injury, laryngeal injury, and pneumothorax. Late complications included significant granulation tissue formation in metallic stents and lung collapse because of mucus plug. The survival rates at 4, 8, and 12 weeks were 83%, 70.7%, and 66.1%, respectively. Significant improvement was observed in dyspnea, cough, Speiser Score, 6MWD, forced expiratory volume in 1 s, forced vital capacity, and SGRQ scores at 48 hours, 4 weeks, and at 12 weeks after the procedures and no procedure-related mortality occurred. Conclusion: Various therapeutic bronchoscopic interventions, including combined modalities, provide rapid and sustained improvements in symptoms, respiratory status, exercise capacity, and quality of life in malignant CAO and have a good safety profile. Disclosure: There is no conflict of interest or other disclosures. Reprints: Anant Mohan, MD, PhD, FRCP, Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi 110029, India (e-mail: anantmohan@yahoo.com). Received September 30, 2017 Accepted August 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Assessment of Ergonomic Strain and Positioning During Bronchoscopic Procedures: A Feasibility Study Background: Poor ergonomics place health care workers at risk for work-related overuse injuries. Repetitive and prolonged hand maneuvers, such as those performed during endoscopic procedures, may lead to musculoskeletal complaints and work-related injuries. However, the prevalence of health care–related work injuries among physicians is thought to be underreported and there is a paucity of literature investigating the impact of ergonomic strain on bronchoscopy. We designed a feasibility study to explore the differences in ergonomic strain and muscle activity of bronchoscopists. Materials and Methods: A prospective study of bronchoscopic procedures was performed in a simulated environment. Preselected target areas were identified and airway sampling was performed with real-time ergonomic assessment utilizing electromyogram (EMG), grip strength, and musculoskeletal use and motion analysis. Results: Procedural data was obtained for all procedures (78 bronchoscopies by 13 subjects) for both ergonomic and EMG scores. Experienced bronchoscopists demonstrated less EMG burden (P=0.007) and improved ergonomic positioning (P=0.007) during bronchoscopy when compared with less experienced bronchoscopists. Procedures performed with rotational-head bronchoscopes trended toward improved ergonomics (P=0.15) and lower EMG scores (P=0.88). A significant improvement in ergonomic scores was seen with the rotational-head bronchoscope when targeting the left upper lobe (P=0.036). Conclusion: Poor ergonomic positioning and excessive muscle strain appear present within bronchoscopy procedures but may be improved in those with more bronchoscopy experience. Technological advances in bronchoscope design may also have the potential to improve procedural ergonomics. Additional prospective studies are warranted to define the long-term impact on bronchoscopic ergonomics. C.R.G. and J.T.: contributed equally.C.R.G., J.T., C.M., A.C., N.J.P., A.C.A., J.M., R.A.L., A.D.L., D.H.Y., B.S., D.L., H.J.L., L.B.Y. all contributed to study design, data acquisition, and analysis, drafting of the manuscript, final approval of the manuscript. All authors agree to be accountable for all aspects of the final submitted manuscript. Supported by research funding/equipment/support from Olympus Corporation of the Americas. The study sponsors did not participate in study design, data collection, data analysis, data interpretation, manuscript preparation, final manuscript approval, and/or the decision to submit the manuscript. This study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number T32HL007534 and F32HL144121-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosure: C.R.G., A.C., N.J.P., A.C.A., L.B.Y., have worked in the past and/or are currently consultants for Olympus Corporation of the Americas. The remaining authors declare no conflicts of interest or other disclosures. Reprints: Christopher R. Gilbert, DO, MS, Division of Thoracic Surgery and Interventional Pulmonology, Swedish Cancer Institute, 1101 Madison Street, Suite 900, Seattle, WA 98104 (e-mail: christopher.gilbert@swedish.org). Received March 27, 2019 Accepted July 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Programmed Death Ligand 1 Testing of Endobronchial Ultrasound–guided Transbronchial Needle Aspiration Samples Acquired For the Diagnosis and Staging of Non–Small Cell Lung Cancer Rationale: Immunotherapy has become an integral part of management in patients with advanced non–small cell lung cancer (NSCLC). Programmed death ligand 1 (PD-L1) expression in at least 50% of tumor cells on histologic samples has been correlated with improved efficacy of the immune checkpoint inhibitor pembrolizumab. A limited number of studies have examined the suitability of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) specimens for assessment of PD-L1 status. Objective: We sought to examine the feasibility and results of PD-L1 testing performed on EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Materials and Methods: Patients were identified from a prospectively maintained pathology database. Baseline characteristics were tabulated. Hematoxylin and eosin slides were reviewed to categorize cellularity between <100, 100 to 500, and >500 viable tumor cells. Samples were tested using Dako’s PD-L1 IHC 22C3 pharmDx kit, with a minimum of 100 viable tumor cells. For patients in whom additional tissue samples were available, the results of PD-L1 testing were compared. Results: PD-L1 testing was attempted on 120 EBUS-TBNA samples. The most common NSCLC subtype was adenocarcinoma (78%). Seventy-six specimens (63%) had a cellularity >500 tumor cells. Among 110 of 120 (92%) patients with an adequate endobronchial ultrasound (EBUS) sample, 53 of 110 (48.2%) had high PD-L1 expression, defined as a Tumor Proportion Score ≥50%. EBUS PD-L1 results were concordant with an available histologic sample in 14 of 18 patients (78%), with no false-negative results. Conclusion: PD-L1 testing was feasible in the majority of EBUS-TBNA samples acquired for the diagnosis and staging of NSCLC. Comparison of EBUS results with histologic samples revealed moderate concordance, with no false-negative results. Supported by Rossy Cancer Network Research Fund. Disclosure: A.V.G. was the recipient of an FRQS chercheur-boursier-clinicien award and holds a grant from the Rossy Cancer Network. H.W. reports personal fees from Pfizer, Merck, and AstraZeneca, outside the submitted work. P.-O.F. reports personal fees from AstraZeneca, Merck, and Pfizer, outside the submitted work. The remaning authors have no conflict of interest or other disclosures. Reprints: Anne V. Gonzalez, MD, MSc, Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre Research Institute, 5252 Boul. de Maisonneuve West, 3D.63, Montreal, QC, Canada H4A 3S5 (e-mail: anne.gonzalez@mcgill.ca). Received March 10, 2019 Accepted August 5, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Patient-controlled Sedation During Flexible Bronchoscopy: A Randomized Controlled Trial Background: Patient-controlled sedation (PCS) is a documented method for endoscopic procedures considered to facilitate early recovery. Limited data have been reported, however, on its use during flexible bronchoscopy (FB). Materials and Methods: This study hypothesized that PCS with propofol during FB would facilitate early recovery, with similar bronchoscopist and patient satisfaction compared with nurse-controlled sedation (NCS) with midazolam. A total of 150 patients were randomized 1:1:1 into a control group (premedication with morphine-scopolamine and NCS with midazolam), PCS-MS group (premedication with morphine-scopolamine and PCS with propofol), and PCS-G group (premedication with glycopyrronium and PCS with propofol). Results: The procedures included transbronchial biopsy, transbronchial needle aspiration, cryotherapy/biopsy, and/or multistation endobronchial ultrasound. FB duration values in median (range) were 40 (10 to 80), 39 (12 to 68), and 44 (10 to 82) minutes for the groups NCS, PCS-MS, and PCS-G, respectively. An overall 81% of the patients in the combined PCS groups were ready for discharge (modified Post Anaesthetic Discharge Scoring System, score 10) 2 hours after bronchoscopy compared with 40% in the control group (P<0.0001). Between PCS groups, 96% of the PCS-G group patients were ready for discharge compared with 65% in the PCS-MS group (P=0.0002) at 2 hours. Bronchoscopists’ and patients’ satisfaction scores were high in all groups. Postdischarge quality scores showed no differences among the groups. Conclusion: PCS with propofol during FB is feasible, as it shortened recovery time without compromising procedure conditions for bronchoscopists or patients. A rapid postsedation stabilization of vital signs facilitates surveillance before the patient leaves the hospital. Supported by internal grants from Region of Östergötland, Sweden. Disclosure: There is no conflict of interest or other disclosures. Reprints: Benjamin Grossmann, PhD, Linköping University Hospital, Linko[Combining Diaeresis]ping S-581 85, Sweden (e-mail: benjamin.grossmann@regionostergotland.se). Received December 20, 2018 Accepted June 11, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Rigid Mini-Thoracoscopy Versus Semirigid Thoracoscopy in Undiagnosed Exudative Pleural Effusion: The MINT Randomized Controlled Trial Background: There is debate regarding the ideal instrument for medical thoracoscopy. The authors compared rigid mini-thoracoscopy with semirigid thoracoscopy for thoracoscopic pleural biopsy. Methods: Consecutive subjects with undiagnosed exudative pleural effusion were randomized (1:1 ratio) to mini-thoracoscopy or semirigid thoracoscopy groups. The primary objective was a comparison of the diagnostic yield of pleural biopsy. Key secondary outcomes were the comparison of sedative/analgesic dose, operator-rated and patient-rated pain on visual analog scale (VAS), operator-rated overall procedural satisfaction (VAS), pleural biopsy size, and complications between the groups. Results: Of the 88 screened subjects, 73 were randomized: 36 to mini-thoracoscopy and 37 to semirigid thoracoscopy. Diagnostic yield of pleural biopsy in the mini-thoracoscopy (69.4%) and semirigid thoracoscopy groups (81.1%) was similar on intention-to-treat analysis (P=0.25). Although the operator-rated overall procedure satisfaction scores were similar between groups (P=0.87), operator-rated pain [VAS (mean±SD), 43.5±16.7 vs. 31.7±15.8; P<0.001] and patient-rated pain (VAS, 41.9±17.3 vs. 32.1±16.5; P=0.02) scores were greater in the mini-thoracoscopy group. Mean dose of fentanyl and midazolam received was similar between the 2 groups (P=0.28 and 0.68, respectively). Biopsy size was larger in the mini-thoracoscopy group (16.1±4.5 vs. 8.3±2.9 mm; P<0.001). Three minor complications occurred in the mini-thoracoscopy group and 6 in the semirigid thoracoscopy group (P=0.11). There were no serious adverse events or procedure-related mortality. Conclusion: Diagnostic yield of rigid mini-thoracoscopy is not superior to semirigid thoracoscopy. Use of semirigid thoracoscope may provide greater patient comfort. S.B.: collected data, data analysis, prepared the manuscript. S.M. and P.T.: collected data and manuscript revision. D.J. and S.A.: reported the pathology specimens and revised the manuscript. V.H., A.M., P.M., G.C.K., and R.G.: study design and manuscript revision. R.M.P.: data analysis and manuscript revision. K.M.: conceived the study, study design, manuscript preparation, and revision of the manuscript. There is no conflict of interest or other disclosures. Reprints: Karan Madan, MD, DM, Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi 110029, India (e-mail: drkaranmadan@gmail.com). Received April 11, 2019 Accepted July 29, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Predictors of Intraprocedural Respiratory Bronchoscopy Complications Purpose: Sleep apnea can increase adverse outcomes during ambulatory surgery but not during gastrointestinal endoscopy. We hypothesize that STOP-BANG is associated with intraprocedural bronchoscopy respiratory complications. Materials and Methods: Consecutive patients undergoing bronchoscopy under moderate sedation were prospectively administered the STOP-BANG questionnaire. Participants were assessed for intraprocedural complications including hypoxemia (oxygen saturation≤85%), bradypnea (respiratory rate<8), premature procedure cessation as well as the use of nonrebreather mask, bag-mask ventilation, jaw lift/chin tilt, nasal/oral airway, and naloxone administration. Associations were assessed via logistic regression. Least absolute shrinkage and selection operator was used for multivariable model variable selection. Results: The 223 participants—mean age 61.1±15.5 years, body mass index 25.4kg/m2 (interquartile range: 22.4 to 30.7), 50.7% female, and 45.3% inpatient—had a high rate of respiratory complications (37.7%). There were no associations between STOP-BANG score and respiratory complications [odds ratio (OR)=1.07, 95% confidence interval (CI): 0.92-1.25]. Asthma was protective in univariable models (OR=0.26, 95% CI: 0.04-0.98), whereas endobronchial ultrasound (OR=2.34, 95% CI: 1.35-4.10) and the number of procedure types (OR=1.24, 95% CI: 1.01-1.51) was associated with increased complications. The following factors were associated with respiratory complications in both multivariable and univariate analyses: increasing age (OR=1.28/decade, 95% CI: 1.03-1.61), baseline oxygen use per each liters per minute (OR=1.57, 95% CI: 1.21-2.09), and bronchoscopy duration (OR=1.20/10 min, 95% CI: 1.08-1.33). Conclusion: Bronchoscopy respiratory complications are common. STOP-BANG was not associated with increased immediate bronchoscopy complication risk. Increasing age, oxygen use, and bronchoscopy duration were associated with respiratory complications; increased vigilance in these circumstances may prevent complications. Supported by funds from the National Institutes of Health (NIH) National Heart Lung Blood Institute (NHLBI) T32 HL/NS 007913 Sleep Medicine Neurobiology and Epidemiology grant and the American Thoracic Society ASPIRE fellowship. The sponsors did not participate in the design or conduct of the study; collection, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Disclosure: K.P.S. receives research support from Inspire Medica Systems, and is a consultant for Galvani Bioelectronics, Jazz Pharmaceuticals, Sommetrics, and Seven Dreamers. The remaining authors there are no conflict of interest or other disclosures. Reprints: Anna M. May, MD, MS, Louis Stokes Cleveland VA Medical Center, Pulmonary 111J(W), 10701 East Boulevard, Cleveland, OH 44106 (e-mail: drannamay@gmail.com). Received April 5, 2019 Accepted July 26, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Combined Thoracoscopic Surgical Stapling and Endobronchial Valve Placement For Lung Volume Reduction With Incomplete Lobar Fissures: An Experimental Pilot Animal Study Background: In patients with severe emphysema and complete fissures, bronchoscopic lung volume reduction with valves reduces target lobe volume providing improvement in respiratory symptoms, lung function, quality of life, and exercise capacity. It is estimated that up to 88% of patients with emphysema have at least 1 incomplete interlobar fissure. The aim of this study was to evaluate the feasibility of creating a complete fissure with stapling via minimally invasive video-assisted thoracoscopic surgery (VATS) followed by bronchoscopic valve placement to induce lobar collapse in a swine model. Methods: Chest computed tomography (CT) scans were performed on 2 swine and at least 1 target incomplete fissure was identified. Both swine underwent VATS to complete the target fissure using a surgical stapler, followed by bronchoscopic placement of the Spiration endobronchial valves. A chest CT scan was performed immediately postprocedure. Follow-up bronchoscopy and CT scans were performed 2 weeks after the initial procedure prior to sacrifice. Results: Successful fissure completion was accomplished using VATS and confirmed at postmortem explanted lung gross examination. Flexible bronchoscopy 2 weeks following valve placement showed proper positioning of the valves. Effectiveness of combined procedures was confirmed by a chest CT scan that showed complete atelectasis of the target lobe at 2-week follow-up. There was no perioperative or postoperative morbidity or mortality. Conclusion: Combined minimally invasive VATS fissure stapling with bronchoscopic valve placement to induce lobar atelectasis appears safe and feasible in the swine model. Future research in humans using a combined procedure is needed to confirm safety and clinical efficacy. A.M. and F.K. contributed equally. Supported by Olympus Respiratory America. A.M.: is the guarantor of the content of the manuscript, including the data and analysis, and participated in data analysis, manuscript writing, and manuscript review. F.K., D.A.: participated in data analysis, manuscript writing, and manuscript review. L.D.V., S.G.: participated in data analysis, data collection and manuscript review; A.A., M.P., A.C.: participated in manuscript review. Disclosure: A.M., F.K., and M.P. are educational consultants for Olympus. For the remaining authors there is no conflict of interest or other disclosures. Reprints: Adnan Majid, MD, FCCP, Section of Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Road, Deaconess-201, Boston, MA 02215 (e-mail: amajid@bidmc.harvard.edu). Received March 26, 2019 Accepted July 17, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.