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[PMID]: 26003812
[Au] Autor:Uray T; Mayr FB; Fitzgibbon J; Rittenberger JC; Callaway CW; Drabek T; Fabio A; Angus DC; Kochanek PM; Dezfulian C
[Ad] Address:Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria....
[Ti] Title:Socioeconomic factors associated with outcome after cardiac arrest in patients under the age of 65.
[So] Source:Resuscitation;93:14-9, 2015 Aug.
[Is] ISSN:1873-1570
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:AIM: In a prior study of seven North American cities Pittsburgh had the highest crude rate of cardiac arrest deaths in patients 18 to 64 years of age, particularly in neighborhoods with lower socioeconomic status (SES). We hypothesized that lower SES, associated poor health behaviors (e.g., illicit drug use) and pre-existing comorbid conditions (grouped as socioeconomic factors [SE factors]) could affect the type and severity of cardiac arrest, thus outcomes. METHODS: We retrospectively identified patients aged 18 to 64 years treated for in-hospital (IHCA) and out-of hospital arrest (OHCA) at two Pittsburgh hospitals between January 2010 and July 2012. We abstracted data on baseline demographics and arrest characteristics like place of residence, insurance and employment status. Favorable cerebral performance category [CPC] (1 or 2) was our primary outcome. We examined the associations between SE factors, cardiac arrest variables and outcome as well as post-resuscitation care. RESULTS: Among 415 subjects who met inclusion criteria, unfavorable CPC were more common in patients who were unemployed, had a history of drug abuse or hypertension. In OHCA, favorable CPC was more often associated with presentation with ventricular fibrillation/tachycardia (OR 3.53, 95% CI 1.43-8.74, p=0.006) and less often associated with non-cardiovascular arrest etiology (OR 0.22, 95% CI 0.08-0.62, p=0.004). We found strong associations between specific SE factors and arrest factors associated with outcome in OHCA patients only. Significant differences in post-resuscitation care existed based on injury severity, not on SES. CONCLUSIONS: SE factors strongly influence type and severity of OHCA but not IHCA resulting in an association with outcomes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 4200104 MEDLINE  
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[PMID]: 25917262
[Au] Autor:Sutton RM; Case E; Brown SP; Atkins DL; Nadkarni VM; Kaltman J; Callaway C; Idris A; Nichol G; Hutchison J; Drennan IR; Austin M; Daya M; Cheskes S; Nuttall J; Herren H; Christenson J; Andrusiek D; Vaillancourt C; Menegazzi JJ; Rea TD; Berg RA; ROC Investigators
[Ad] Address:The Children's Hospital of Philadelphia, 34th Street, Civic Center Boulevard, Philadelphia, PA 19104, United States. Electronic address: suttonr@chop.edu....
[Ti] Title:A quantitative analysis of out-of-hospital pediatric and adolescent resuscitation quality - A report from the ROC epistry-cardiac arrest.
[So] Source:Resuscitation;93:150-7, 2015 Aug.
[Is] ISSN:1873-1570
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:AIM: High-quality cardiopulmonary resuscitation (CPR) may improve survival. The quality of CPR performed during pediatric out-of-hospital cardiac arrest (p-OHCA) is largely unknown. The main objective of this study was to describe the quality of CPR performed during p-OHCA resuscitation attempts. METHODS: Prospective observational multi-center cohort study of p-OHCA patients ≥1 and <19 years of age registered in the Resuscitation Outcomes Consortium (ROC) Epistry database. The primary outcome was an a priori composite variable of compliance with American Heart Association (AHA) guidelines for both chest compression (CC) rate and CC fraction (CCF). Event compliance was defined as a case with 60% or more of its minute epochs compliant with AHA targets (rate 100-120min(-1); depth ≥38mm; and CCF ≥0.80). In a secondary analysis, multivariable logistic regression was used to evaluate the association between guideline compliance and return of spontaneous circulation (ROSC). RESULTS: Between December 2005 and December 2012, 2564 pediatric events were treated by EMS providers, 390 of which were included in the final cohort. Of these events, 22% achieved AHA compliance for both rate and CCF, 36% for rate alone, 53% for CCF alone, and 58% for depth alone. Over time, there was a significant increase in CCF (p<0.001) and depth (p=0.03). After controlling for potential confounders, there was no significant association between AHA guideline compliance and ROSC. CONCLUSIONS: In this multi-center study, we have established that there are opportunities for professional rescuers to improve prehospital CPR quality. Encouragingly, CCF and depth both increased significantly over time.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 4200104 MEDLINE  
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[PMID]: 26012362
[Au] Autor:Masarova L; Newberry KJ; Pierce SA; Estrov Z; Cortes JE; Kantarjian HM; Verstovsek S
[Ad] Address:Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA....
[Ti] Title:Association of lymphoid malignancies and Philadelphia-chromosome negative myeloproliferative neoplasms: Clinical characteristics, therapy and outcome.
[So] Source:Leuk Res;39(8):822-7, 2015 Aug.
[Is] ISSN:1873-5835
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The co-occurrence of myeloproliferative and lymphoproliferative neoplasms (MPN/LPN) has been reported, mostly in case reports. The aim of this study was to assess the characteristics and clinical course of the coexistent diseases. Among 9866 patients who presented to our institution from 1960 to 2014, 34 (0.3%) were diagnosed with MPN/LPN. LPN was diagnosed first in 16 patients, second in 15, and at the same time in 3. The time to secondary malignancy was longer when LPN was diagnosed first (119 vs 98 months). Myelofibrosis (41%), polycythemia vera (24%), and essential thrombocythemia (18%) were the most common MPNs, and non-Hodgkin lymphoma (50%) and chronic lymphocytic leukemia (32%) were the most common LPNs. Seventy-three percent of patients treated for MPN and 72% of those treated for LPN achieved a complete response. After a median follow-up from MPN diagnosis of 84 months, 16 patients are alive and 18 died (4 related to MPN and 2 LPN). Coexistent MPN/LPN is a rare event that does not appear to predict worse outcomes. Treatment choice is generally oriented towards controlling the prevalent disease; the other malignancy may influence treatment strategies in selected cases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 4200104 MEDLINE  
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[PMID]: 26060224
[Au] Autor:Dusetzina SB; Ellis S; Freedman RA; Conti RM; Winn AN; Chambers JD; Alexander GC; Huskamp HA; Keating NL
[Ad] Address:UNC Eshelman School of Pharmacy; University of North Carolina at Chapel Hill, Gillings School of Global Public Health; UNC Lineberger Comprehensive Cancer Center; Cecil G. Sheps Center for Health Services Research, Chapel Hill, NC; University of Kansas School of Medicine, Kansas City, KS; Dana-Farbe...
[Ti] Title:How Do Payers Respond to Regulatory Actions? The Case of Bevacizumab.
[So] Source:J Oncol Pract;11(4):313-8, 2015 Jul.
[Is] ISSN:1935-469X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: In February 2008, the US Food and Drug Administration (FDA) granted accelerated approval for bevacizumab for metastatic breast cancer. After public hearings in July 2010, and June 2011, the FDA revoked this approved indication in November 2011, on the basis of additional evidence regarding its risk/benefit profile. The Centers for Medicare and Medicaid Services, local Medicare contractors, and commercial payers varied in their stated intentions to cover bevacizumab after FDA's regulatory actions. We examined payer-specific trends in bevacizumab use after the FDA's regulatory actions. METHODS: We used outpatient medical claims compiled by IMS Health to evaluate trends in bevacizumab use for breast cancer for Medicare-insured and commercially insured patients (N = 102,906) using segmented regression. Given that Medicare coverage policies may vary across regional contractors, we estimated trends in bevacizumab use across 10 local coverage areas. In a sensitivity analysis, we estimated trends in bevacizumab use for breast cancer compared with trends in use for lung cancer using difference-in-differences models. RESULTS: Among chemotherapy infusions for breast cancer, bevacizumab use decreased from 31% in July 2010, to 4% in September 2012. Use decreased by 11% among commercially insured and 13% among Medicare-insured patients after July 2010 (interaction P = .68) and continued to decline by 9% per month (interaction P = .61). We observed no contractor-level variation in bevacizumab use among Medicare beneficiaries. During the same period, bevacizumab use for lung cancer was stable. CONCLUSION: Although insurers varied in public statements regarding coverage intentions, bevacizumab use declined similarly among all payers, suggesting that provider decision making, rather than payer-specific coverage policies, drove reductions.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1200/JOP.2015.004218

  5 / 4200104 MEDLINE  
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[PMID]: 26115192
[Au] Autor:Wthrich C; Batson S; Koralnik IJ
[Ad] Address:From the Division of Neuro-Immunology, Department of Neurology, Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
[Ti] Title:Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System.
[So] Source:J Neuropathol Exp Neurol;74(8):791-803, 2015 Aug.
[Is] ISSN:1554-6578
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 control subjects. Neurons predominantly sustained a restrictive infection with expression of JCV regulatory protein T antigen (T Ag), whereas glial cells were productively infected and expressed both T Ag and the capsid protein VP1. T cells were more prevalent near JCV-infected cells with intact nuclei expressing both T Ag and VP1 compared with those expressing either protein alone. CD8-positive T cells also colocalized more with JCV-infected glial cells than with JCV-infected neurons. Major histocompatibility complex class I expression was upregulated in JCV-infected areas but could only be detected in rare neurons interspersed with infected glial cells. These results suggest that isolated neurons harboring restrictive JCV infection do not upregulate major histocompatibility complex class I and thus may escape recognition by CD8-positive T cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1097/NEN.0000000000000218

  6 / 4200104 MEDLINE  
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[PMID]: 26136429
[Au] Autor:Mongini PK; Gupta R; Boyle E; Nieto J; Lee H; Stein J; Bandovic J; Stankovic T; Barrientos J; Kolitz JE; Allen SL; Rai K; Chu CC; Chiorazzi N
[Ad] Address:The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY 11030; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY 11549; pmongini@nshs.edu....
[Ti] Title:TLR-9 and IL-15 Synergy Promotes the In Vitro Clonal Expansion of Chronic Lymphocytic Leukemia B Cells.
[So] Source:J Immunol;195(3):901-23, 2015 Aug 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Clinical progression of B cell chronic lymphocytic leukemia (B-CLL) reflects the clone's Ag receptor (BCR) and involves stroma-dependent B-CLL growth within lymphoid tissue. Uniformly elevated expression of TLR-9, occasional MYD88 mutations, and BCR specificity for DNA or Ags physically linked to DNA together suggest that TLR-9 signaling is important in driving B-CLL growth in patients. Nevertheless, reports of apoptosis after B-CLL exposure to CpG oligodeoxynucleotide (ODN) raised questions about a central role for TLR-9. Because normal memory B cells proliferate vigorously to ODN+IL-15, a cytokine found in stromal cells of bone marrow, lymph nodes, and spleen, we examined whether this was true for B-CLL cells. Through a CFSE-based assay for quantitatively monitoring in vitro clonal proliferation/survival, we show that IL-15 precludes TLR-9-induced apoptosis and permits significant B-CLL clonal expansion regardless of the clone's BCR mutation status. A robust response to ODN+IL-15 was positively linked to presence of chromosomal anomalies (trisomy-12 or ataxia telangiectasia mutated anomaly + del13q14) and negatively linked to a very high proportion of CD38(+) cells within the blood-derived B-CLL population. Furthermore, a clone's intrinsic potential for in vitro growth correlated directly with doubling time in blood, in the case of B-CLL with Ig H chain V region-unmutated BCR and <30% CD38(+) cells in blood. Finally, in vitro high-proliferator status was statistically linked to diminished patient survival. These findings, together with immunohistochemical evidence of apoptotic cells and IL-15-producing cells proximal to B-CLL pseudofollicles in patient spleens, suggest that collaborative ODN and IL-15 signaling may promote in vivo B-CLL growth.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1403189

  7 / 4200104 MEDLINE  
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[PMID]: 26116506
[Au] Autor:Wang Y; Miwa T; Ducka-Kokalari B; Redai IG; Sato S; Gullipalli D; Zangrilli JG; Haczku A; Song WC
[Ad] Address:Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;...
[Ti] Title:Properdin Contributes to Allergic Airway Inflammation through Local C3a Generation.
[So] Source:J Immunol;195(3):1171-81, 2015 Aug 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Complement is implicated in asthma pathogenesis, but its mechanism of action in this disease remains incompletely understood. In this study, we investigated the role of properdin (P), a positive alternative pathway complement regulator, in allergen-induced airway inflammation. Allergen challenge stimulated P release into the airways of asthmatic patients, and P levels positively correlated with proinflammatory cytokines in human bronchoalveolar lavage (BAL). High levels of P were also detected in the BAL of OVA-sensitized and challenged but not naive mice. Compared with wild-type (WT) mice, P-deficient (P(-/-)) mice had markedly reduced total and eosinophil cell counts in BAL and significantly attenuated airway hyperresponsiveness to methacholine. Ab blocking of P at both sensitization and challenge phases or at challenge phase alone, but not at sensitization phase alone, reduced airway inflammation. Conversely, intranasal reconstitution of P to P(-/-) mice at the challenge phase restored airway inflammation to wild-type levels. Notably, C3a levels in the BAL of OVA-challenged P(-/-) mice were significantly lower than in wild-type mice, and intranasal coadministration of an anti-C3a mAb with P to P(-/-) mice prevented restoration of airway inflammation. These results show that P plays a key role in allergen-induced airway inflammation and represents a potential therapeutic target for human asthma.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1401819

  8 / 4200104 MEDLINE  
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[PMID]: 25769142
[Au] Autor:Matzuka B; Mehlsen J; Tran H; Olufsen MS
[Ti] Title:Using Kalman Filtering to Predict Time-Varying Parameters in a Model Predicting Baroreflex Regulation During Head-Up Tilt.
[So] Source:IEEE Trans Biomed Eng;62(8):1992-2000, 2015 Aug.
[Is] ISSN:1558-2531
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The cardiovascular control system is continuously engaged to maintain homeostasis, but it is known to fail in a large cohort of patients suffering from orthostatic intolerance. Numerous clinical studies have been put forward to understand how the system fails, yet noninvasive clinical data are sparse, typical studies only include measurements of heart rate and blood pressure, as a result it is difficult to determine what mechanisms that are impaired. It is known, that blood pressure regulation is mediated by changes in heart rate, vascular resistance, cardiac contractility, and a number of other factors. Given that numerous factors contribute to changing these quantities, it is difficult to devise a physiological model describing how they change in time. One way is to build a model that allows these controlled quantities to change and to compare dynamics between subject groups. To do so, it requires more knowledge of how these quantities change for healthy subjects. This study compares two methods predicting time-varying changes in cardiac contractility and vascular resistance during head-up tilt. Similar to the study by Williams etal. [51], the first method uses piecewise linear splines, while the second uses the ensemble transform Kalman filter (ETKF) [1], [11], [12], [33]. In addition, we show that the delayed rejection adaptive Metropolis (DRAM) algorithm can be used for predicting parameter uncertainties within the spline methodology, which is compared with the variability obtained with the ETKF. While the spline method is easier to set up, this study shows that the ETKF has a significantly shorter computational time. Moreover, while uncertainty of predictions can be augmented to spline predictions using DRAM, these are readily available with the ETKF.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1109/TBME.2015.2409211

  9 / 4200104 MEDLINE  
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[PMID]: 26052898
[Au] Autor:Styner M; Pagnotti GM; Galior K; Wu X; Thompson WR; Uzer G; Sen B; Xie Z; Horowitz MC; Styner MA; Rubin C; Rubin J
[Ad] Address:Department of Medicine (M.S., K.G., X.W., G.U., B.S., Z.X., J.R.), University of North Carolina, Chapel Hill, North Carolina; Department of Physical Therapy (W.R.T.), Indiana University, Indianapolis, Indiana; Department of Computer Science (M.A.S.), University of North Carolina, Chapel Hill, North ...
[Ti] Title:Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice.
[So] Source:Endocrinology;156(8):2753-61, 2015 Aug.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The contribution of marrow adipose tissue (MAT) to skeletal fragility is poorly understood. Peroxisome proliferator-activated receptor (PPAR)γ agonists, associated with increased fractures in diabetic patients, increase MAT. Here, we asked whether exercise could limit the MAT accrual and increase bone formation in the setting of PPARγ agonist treatment. Eight-week-old female C57BL/6 mice were treated with 20-mg/kgd rosiglitazone (Rosi) and compared with control (CTL) animals. Exercise groups ran 12 km/d when provided access to running wheels (CTL exercise [CTL-E], Rosi-E). After 6 weeks, femoral MAT (volume of lipid binder osmium) and tibial bone morphology were assessed by microcomputer tomography. Rosi was associated with 40% higher femur MAT volume compared with CTL (P < .0001). Exercise suppressed MAT volume by half in CTL-E mice compared with CTL (P < .01) and 19% in Rosi-E compared with Rosi (P < .0001). Rosi treatment increased fat markers perilipin and fatty acid synthase mRNA by 4-fold (P < .01). Exercise was associated with increased uncoupling protein 1 mRNA expression in both CTL-E and Rosi-E groups (P < .05), suggestive of increased brown fat. Rosi increased cortical porosity (P < .0001) but did not significantly impact trabecular or cortical bone quantity. Importantly, exercise induction of trabecular bone volume was not prevented by Rosi (CTL-E 21% > CTL, P < .05; Rosi-E 26% > Rosi, P < .01). In summary, despite the Rosi induction of MAT extending well into the femoral diaphysis, exercise was able to significantly suppress MAT volume and induce bone formation. Our results suggest that the impact of PPARγ agonists on bone and marrow health can be partially mitigated by exercise.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1210/en.2015-1213

  10 / 4200104 MEDLINE  
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[PMID]: 25943307
[Au] Autor:Flanigan PM; Aghi MK
[Ad] Address:Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA.
[Ti] Title:Adaptation to antiangiogenic therapy in neurological tumors.
[So] Source:Cell Mol Life Sci;72(16):3069-82, 2015 Aug.
[Is] ISSN:1420-9071
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:Because tumors require a vascular supply for their survival and growth, angiogenesis is considered an important therapeutic target in most human cancers including cancer of the central nervous system. Antiangiogenic therapy has focused on inhibitors of the vascular endothelial growth factor (VEGF) signaling pathway. VEGF pathway-targeted drugs have shown therapeutic efficacy in several CNS tumors and have been tried most frequently in glioblastoma. These therapies, however, have been less effective than anticipated as some patients do not respond to therapy and some receive only modest benefit. Underlying this suboptimal response are multiple mechanisms of drug resistance involving changes in both tumor cells and their microenvironment. In this review, we discuss the multiple proposed mechanisms by which neurological tumors evolve to become resistant to antiangiogenic therapies. A better understanding of these mechanisms, their context, and their interplay will likely facilitate improvements in pharmacological strategies for the targeted treatment of neurological tumors.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1507
[Cu] Class update date: 150718
[Lr] Last revision date:150718
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1007/s00018-015-1916-0


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