| 1. |
- Adare, A., et al.
(författare)
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Measurement of higher cumulants of net-charge multiplicity distributions in Au plus Au collisions at root s(NN)=7.7-200 GeV
- 2016
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 93:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the measurement of cumulants (C-n,n = 1, ..., 4) of the net-charge distributions measured within pseudorapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(NN) = 7.7-200 GeV with the PHENIX experiment at the Relativistic Heavy Ion Collider. The ratios of cumulants (e.g., C-1/C-2, C-3/C-1) of the net-charge distributions, which can be related to volume independent susceptibility ratios, are studied as a function of centrality and energy. These quantities are important to understand the quantum-chromodynamics phase diagram and possible existence of a critical end point. The measured values are very well described by expectation from negative binomial distributions. We do not observe any nonmonotonic behavior in the ratios of the cumulants as a function of collision energy. The measured values of C-1/C-2 and C-3/C-1 can be directly compared to lattice quantum-chromodynamics calculations and thus allow extraction of both the chemical freeze-out temperature and the baryon chemical potential at each center-of-mass energy. The extracted baryon chemical potentials are in excellent agreement with a thermal-statistical analysis model.
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| 2. |
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| 3. |
- Adare, A., et al.
(författare)
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Inclusive cross section and double-helicity asymmetry for pi(0) production at midrapidity in p plus p collisions at root s=510 GeV
- 2016
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 93:1
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Tidskriftsartikel (refereegranskat)abstract
- PHENIX measurements are presented for the cross section and double-helicity asymmetry (A(LL)) in inclusive pi(0) production at midrapidity from p + p collisions at root s = 510 GeV from data taken in 2012 and 2013 at the Relativistic Heavy Ion Collider. The next-to-leading-order perturbative-quantum-chromodynamics theory calculation is in excellent agreement with the presented cross section results. The calculation utilized parton-to-pion fragmentation functions from the recent DSS14 global analysis, which prefer a smaller gluon-to-pion fragmentation function. The pi(0)A(LL) results follow an increasingly positive asymmetry trend with p(T) and root s with respect to the predictions and are in excellent agreement with the latest global analysis results. This analysis incorporated earlier results on pi(0) and jet A(LL) and suggested a positive contribution of gluon polarization to the spin of the proton Delta G for the gluon momentum fraction range x > 0.05. The data presented here extend to a currently unexplored region, down to x similar to 0.01, and thus provide additional constraints on the value of Delta G.
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| 4. |
- Adare, A., et al.
(författare)
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Nuclear matter effects on J/psi production in asymmetric Cu plus Au collisions at root S-NN=200 GeV
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:6
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Tidskriftsartikel (refereegranskat)abstract
- We report on J/psi production from asymmetric Cu + Au heavy-ion collisions at root S-NN = 200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of J/psi yields in Cu + Au collisions in the Au-going direction is found to be comparable to that inAu + Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, J/psi production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-x gluon suppression in the larger Au nucleus.
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| 5. |
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| 6. |
- Sweeney, M. D., et al.
(författare)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 7. |
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| 8. |
- Chen, Robert, et al.
(författare)
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Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma
- 2017
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 35:19, s. 2125-2132
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response >= 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
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| 9. |
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| 10. |
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| 11. |
- Riquelme, M. V. P., et al.
(författare)
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Demonstrating a Comprehensive Wastewater-Based Surveillance Approach That Differentiates Globally Sourced Resistomes
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:21, s. 14982-14993
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Tidskriftsartikel (refereegranskat)abstract
- Wastewater-based surveillance (WBS) for disease monitoring is highly promising but requires consistent method-ologies that incorporate predetermined objectives, targets, and metrics. Herein, we describe a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage that enables assessment of 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends in ARGs, such as antibiotic concentrations. Across an internationally sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Regional trends in measured antibiotic concentrations differed from trends expected from public sales data. This could reflect unaccounted uses, captured only by the WBS approach. If properly benchmarked, antibiotic WBS might complement public sales and consumption statistics in the future. The WBS approach defined herein demonstrates multisite comparabyility and sensitivity to local/regional factors.
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| 12. |
- Armand, Philippe, et al.
(författare)
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Five-year follow-up of KEYNOTE-087 : pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:10, s. 878-886
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Tidskriftsartikel (refereegranskat)abstract
- Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for <= 2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for >= 4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.
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| 13. |
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| 14. |
- Cheah, Chan Y., et al.
(författare)
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Clinical characteristics and outcomes of patients with Hodgkin lymphoma with central nervous system involvement : An international multicenter collaboration
- 2016
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Ingår i: American Journal of Hematology. - : Wiley. - 0361-8609. ; 91:9, s. 894-899
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement is rare in patients with Hodgkin lymphoma (HL). Thus, the clinical features and outcomes are not well described. Cases of histologically confirmed CNS HL diagnosed between 1995 and 2015 were retrospectively identified in institutional (n = 7), national (n = 2), and cooperative group (n = 1) databases. We screened 30,781 patients with HL in our combined databases and identified 21 patients meeting eligibility criteria, an estimated frequency of 0.07%. CNS involvement was present at initial diagnosis in 10 patients (48%) and a feature of relapsed/refractory disease in 11 (52%). Among these 11 patients, the median time from initial diagnosis of HL to development of CNS involvement was 1.9 years (range 0.4–6.6) and the median number of prior lines of therapy was 2 (range 1–7). Altogether, treatments included radiation, multiagent systemic chemotherapy, combined modality therapy, and subtotal resection. The overall response rate was 65%. After a median follow-up of 3.6 years (range 0.8–13.2) from diagnosis of CNS HL, the median PFS and OS were 7.6 and 29 months, respectively. CNS involvement as a feature of relapsed/refractory disease was adversely prognostic for both PFS and OS; however, four patients remain alive and free of relapse at 7–78 months follow-up. CNS involvement in HL is exceedingly rare and has a distinct clinical presentation with predilection for parenchymal lesions with dural extension. Around one-quarter of patients, mostly with CNS involvement at initial HL diagnosis, experience prolonged disease-free survival. Am. J. Hematol. 91:894–899, 2016.
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| 15. |
- Chen, Robert, et al.
(författare)
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Pembrolizumab in relapsed or refractory Hodgkin lymphoma : 2-year follow-up of KEYNOTE-087
- 2019
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 134:14, s. 1144-1153
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Tidskriftsartikel (refereegranskat)abstract
- Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL.
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| 16. |
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| 17. |
- Kraus, V. B., et al.
(författare)
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Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:5, s. 515-542
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 19. |
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| 20. |
- Christensen, R. H., et al.
(författare)
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Imaging the inflammatory phenotype in migraine
- 2022
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing. We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5). In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.
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| 23. |
- Plesnila, N., et al.
(författare)
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Nuclear translocation of apoptosis-inducing factor after focal cerebral ischemia
- 2004
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Ingår i: J Cereb Blood Flow Metab. ; 24:4, s. 458-66
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Tidskriftsartikel (refereegranskat)abstract
- Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.
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| 24. |
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