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  • 1
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2015-02, Vol.50 (2), p.181-188
    Description: We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.
    Subject(s): Autografts ; Follow-Up Studies ; Leukemia, Myeloid, Acute - pathology ; Humans ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Infant ; Male ; Survival Rate ; Abnormal Karyotype ; Cord Blood Stem Cell Transplantation ; Leukemia, Myeloid, Acute - mortality ; fms-Like Tyrosine Kinase 3 - genetics ; Disease-Free Survival ; Allografts ; Adolescent ; Myeloablative Agonists - administration & dosage ; Female ; Transplantation Conditioning - methods ; Child ; Leukemia, Myeloid, Acute - therapy ; Leukemia, Myeloid, Acute - genetics ; Transplantation ; Health aspects ; Patient outcomes ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2005-12, Vol.36 (11), p.947-950
    Description: We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (〈or=14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n=3), graft failure (n=2), Epstein-Barr virus lymphoma (n=2) and hemorrhage (n=2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults.
    Subject(s): Hematologic and hematopoietic diseases ; Anemias. Hemoglobinopathies ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Diseases of red blood cells ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Biological and medical sciences ; Medical sciences ; Cyclophosphamide - administration & dosage ; Humans ; Child, Preschool ; Vidarabine - analogs & derivatives ; Hematopoietic Stem Cell Transplantation - mortality ; Antilymphocyte Serum - administration & dosage ; Anemia, Aplastic - therapy ; Cause of Death ; Anemia, Aplastic - mortality ; Adolescent ; Hematopoietic Stem Cell Transplantation - adverse effects ; Survival Analysis ; Adult ; Graft Rejection ; Graft vs Host Disease - prevention & control ; Vidarabine - administration & dosage ; Hematopoietic Stem Cell Transplantation - methods ; Tissue Donors ; Transplantation Conditioning - methods ; Drug Therapy, Combination ; Anemia, Aplastic - complications ; Child ; Antimitotic agents ; Complications and side effects ; Patient outcomes ; Aplastic anemia ; Bone marrow ; Dosage and administration ; Transplantation ; Diagnosis ; Antineoplastic agents ; Drug therapy ; Health aspects ; Risk factors
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Journal of medical genetics, 2006-04, Vol.43 (4), p.315-325
    Description: Background: Osteopetrosis, a genetic disease characterised by osteoclast failure, is classified into three forms: infantile malignant autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IRO), and autosomal dominant osteopetrosis (ADO). Methods: We studied 49 patients, 21 with ARO, one with IRO, and 27 with type II ADO (ADO II). Results: Most ARO patients bore known or novel (one case) ATP6i (TCIRG1) gene mutations. Six ADO II patients had no mutations in ClCN7, the only so far recognised gene implicated, suggesting involvement of yet unknown genes. Identical ClCN7 mutations produced differing phenotypes with variable degrees of severity. In ADO II, serum tartrate resistant acid phosphatase was always elevated. Bone alkaline phosphatase (BALP) was generally low, but osteocalcin was high, suggesting perturbed osteoblast differentiation or function. In contrast, BALP was high in ARO patients. Elevated osteoclast surface/bone surface was noted in biopsies from most ARO patients. Cases with high osteoclasts also showed increased osteoblast surface/bone surface. ARO osteoclasts were morphologically normal, with unaltered formation rates, intracellular pH handling, and response to acidification. Their resorption activity was greatly reduced, but not abolished. In control osteoclasts, all resorption activity was abolished by combined inhibition of proton pumping and sodium/proton antiport. Conclusions: These findings provide a rationale for novel therapies targeting pH handling mechanisms in osteoclasts and their microenvironment.
    Subject(s): Cardiology. Vascular system ; General aspects. Genetic counseling ; Biological and medical sciences ; Medical sciences ; Medical genetics ; Vacuolar Proton-Translocating ATPases - genetics ; Osteoclasts - pathology ; Chloride Channels - chemistry ; Sodium-Hydrogen Exchangers - physiology ; Humans ; Child, Preschool ; Osteopetrosis - therapy ; Genotype ; Male ; Chloride Channels - genetics ; Osteocalcin - blood ; Adolescent ; Bone Resorption - pathology ; Bone Resorption - metabolism ; Osteopetrosis - diagnosis ; Adult ; Female ; Phosphoric Monoester Hydrolases - blood ; Osteoclasts - physiology ; Child ; Alkaline Phosphatase - blood ; Osteopetrosis - genetics ; Hydrogen-Ion Concentration ; Genetic aspects ; Osteopetrosis ; Diagnosis ; Hydrogen-ion concentration ; Analysis ; Osteoclasts (Biology) ; Proteins ; Biopsy ; Genes ; Morphology ; Acidification ; Histology ; Mutation ; Deoxyribonucleic acid--DNA ; Index Medicus ; TCIRG1 gene ; osteopetrosis ; ClCN7 gene ; ATP6i ; osteoblast ; osteoclast ; Original
    ISSN: 0022-2593
    ISSN: 1468-6244
    E-ISSN: 1468-6244
    Source: HighWire Press (Free Journals)
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2015-02-01, Vol.50 (2), p.320
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2009-03, Vol.43 (5), p.423-427
    Description: GVHD remains a serious complication after allogeneic SCT. We describe 13 paediatric patients treated with daclizumab for refractory acute GVHD (aGVHD). After 30 days of daclizumab administration, all patients with cutaneous aGVHD reached complete response. Among patients with gastrointestinal disease, 50 and 30% had complete and partial response, respectively, whereas 11 and 55% of patients with hepatic aGVHD achieved CR and PR, respectively. Overall, complete (46%) and partial (46%) responses were demonstrated in 92% of our patients, whereas the remaining patients (8%) were nonresponders. No life-threatening infectious episodes were recorded within 100 days from transplant in this selected group of paediatric patients. Overall 46% of patients were alive at a median of 461 days from SCT, but 50% of them developed chronic GVHD. In our experience, daclizumab proved to be a useful and safe treatment for refractory and steroid-resistant/dependent aGVHD, in particular for cutaneous and low-moderate intestinal involvement.
    Subject(s): Biological and medical sciences ; Medical sciences ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Antibodies, Monoclonal, Humanized ; Acute Disease ; Graft vs Host Disease - drug therapy ; Humans ; Immunosuppressive Agents - therapeutic use ; Hematopoietic Stem Cell Transplantation - adverse effects ; Immunoglobulin G - therapeutic use ; Antibodies, Monoclonal - therapeutic use ; Female ; Male ; Child ; Transplantation, Homologous ; Complications and side effects ; Patient outcomes ; Graft versus host reaction ; Transplantation ; Drug therapy ; Risk factors ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2008-02, Vol.41 (4), p.339-347
    Description: We performed a retrospective single center study to define the epidemiology of bacteremias or invasive mycoses in pediatric allogeneic hematopoietic SCT (HSCT) from matched related donors (MRD) or alternative donors (AD). During 119 213 days of follow-up, 156 infections were observed: 130 bacteremias (27 in MRD-HSCT and 103 in AD-HSCT recipients) and 26 invasive mycoses (8 in MRD-HSCT and 18 in AD-HSCT recipients). Overall, the risk of bacteremia was fivefold that of invasive mycosis (P〈0.001). AD-HSCT recipients had a higher percentage of infections (89 vs 27%; P〈0.001), a higher rate/100 days of immunosuppression (infection rate (IR): 0.21 vs 0.06; P〈0.001) and a higher proportion of repeated infections (44 vs 9%; P=0.001). In AD-HSCT, the relative risk of bacteremia was 2.87 in the pre-engraftment period, 5.84 in the early post-engraftment period and 6.46 in the late post-engraftment period (P〈0.001) compared to MRD-HSCT. Only after 1 year did the epidemiology become similar. The epidemiology of invasive mycoses did not differ significantly between the two types of transplant.
    Subject(s): Infectious diseases ; Bacterial diseases ; Human bacterial diseases ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Biological and medical sciences ; Medical sciences ; Bacterial sepsis ; Mycoses - epidemiology ; Hospitals, Pediatric - statistics & numerical data ; Humans ; Child, Preschool ; Infant ; Incidence ; Adolescent ; Hematopoietic Stem Cell Transplantation - adverse effects ; Bacteremia - epidemiology ; Italy - epidemiology ; Retrospective Studies ; Child ; Cross Infection - epidemiology ; Transplantation, Homologous - adverse effects ; Prevention ; Mycoses ; Transplantation ; Health aspects ; Bacteremia ; Risk factors ; Hematopoietic stem cells ; Methods ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2011-01, Vol.46 (1), p.159-160
    Subject(s): Infectious diseases ; Bacterial diseases ; Human bacterial diseases ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Biological and medical sciences ; Medical sciences ; Bacterial sepsis ; Mycoses - epidemiology ; Graft vs Host Disease - complications ; Humans ; Immunosuppressive Agents - therapeutic use ; Bacteremia - complications ; Child, Preschool ; Immunoglobulin G - therapeutic use ; Incidence ; Receptors, Tumor Necrosis Factor - therapeutic use ; Etanercept ; Graft vs Host Disease - drug therapy ; Immunosuppression - adverse effects ; Adolescent ; Bacteremia - epidemiology ; Italy - epidemiology ; Mycoses - complications ; Child ; Drug Resistance ; Cohort Studies ; Stem Cell Transplantation - adverse effects ; Care and treatment ; Patient outcomes ; Mycoses ; Development and progression ; Graft versus host reaction ; Risk factors ; Bacteremia ; Diseases ; Dosage and administration ; Diagnosis ; Children ; Drug therapy ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: The Lancet (British edition), 2008, Vol.371 (9624), p.1579-1586
    Description: Summary Background Severe graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells. Mesenchymal stem cells modulate immune responses in vitro and in vivo. We aimed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation. Methods Patients with steroid-resistant, severe, acute GVHD were treated with mesenchymal stem cells, derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure, in a multicentre, phase II experimental study. We recorded response, transplantation-related deaths, and other adverse events for up to 60 months' follow-up from infusion of the cells. Findings Between October, 2001, and January, 2007, 55 patients were treated. The median dose of bone-marrow derived mesenchymal stem cells was 1·4×106 (min–max range 0·4–9×106 ) cells per kg bodyweight. 27 patients received one dose, 22 received two doses, and six three to five doses of cells obtained from HLA-identical sibling donors (n=5), haploidentical donors (n=18), and third-party HLA-mismatched donors (n=69). 30 patients had a complete response and nine showed improvement. No patients had side-effects during or immediately after infusions of mesenchymal stem cells. Response rate was not related to donor HLA-match. Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin. Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response (11 [37%] of 30 vs 18 [72%] of 25; p=0·002) and higher overall survival 2 years after haemopoietic-stem-cell transplantation (16 [53%] of 30 vs four [16%] of 25; p=0·018). Interpretation Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD. Funding Swedish Cancer Society, Children's Cancer Foundation, Swedish Research Council, Cancer Society in Stockholm, Cancer and Allergy Foundation, Karolinska Institutet, Istituto Superiore di Sanità, European Union, Regione Lombardia, Fondazione CARIPLO, Associazione Italiana Ricerca contro il Cancro, Compagnia di San Paolo Torino, Progetto CARIGE Cellule Staminali, European Commission, Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Ricerca Finalizzata Regione Liguria 2005 Assistenza Domiciliare, Dutch Programme for Tissue Engineering.
    Subject(s): Internal Medicine ; Graft vs Host Disease - classification ; Graft vs Host Disease - therapy ; Severity of Illness Index ; Follow-Up Studies ; Histocompatibility Testing ; Humans ; Middle Aged ; Male ; Survival Rate ; Treatment Outcome ; Transplantation, Homologous ; Neoplasms - therapy ; Graft vs Host Disease - mortality ; Immunotherapy ; Hematopoietic Stem Cell Transplantation - adverse effects ; Adult ; Female ; Transplantation Conditioning - methods ; Child ; Mesenchymal Stem Cell Transplantation ; Complications and side effects ; Care and treatment ; Usage ; Stem cells ; Graft versus host reaction ; Transplantation ; Research ; Health aspects ; Risk factors ; Hematopoietic stem cells ; Index Medicus ; Abridged Index Medicus ; Medicin och hälsovetenskap
    ISSN: 0140-6736
    ISSN: 1474-547X
    E-ISSN: 1474-547X
    Source: Backfile Package - All of Back Files EBS [ALLOFBCKF]
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2010-06, Vol.45 (6), p.1052-1055
    Description: EBV-associated post transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication that may occur after hemopoietic SCT. We prospectively screened 80 children on a weekly basis using nested quantitative PCR to evaluate EBV genome copies. EBV viral load 〈1000 copies per 10(5) PBMC was observed in 63% of transplants, whereas it was between 1000 and 9999 copies per 10(5) PBMC in 13%, and between 10 000 and 19 999 in 10%, with no significant increase in percentage of CD20+ lymphocytes. Viral load reached 〉 or = 20 000 copies per 10(5) PBMC in 14% of patients, and rituximab was administered to 75% of them. None of the patients except one developed a lymphoproliferative disease. Our study found that only 13% of unrelated donor HSCT recipients had a very high risk of EBV-PTLD defined as 〉 or = 20 000 geq per 10(5) PBMC associated with an increase in CD20+ lymphocyte. We suggest that rituximab could be administered in the presence of very high levels of EBV-DNA viral load or in the presence of mid levels of EBV-DNA viral load associated with an increase in the percentage of CD20+ lymphocytes. Through this approach, we significantly reduced the number of patients treated with rituximab, and consequently the acute and chronic adverse events related to this treatment.
    Subject(s): Infectious diseases ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Viral diseases ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Biological and medical sciences ; Medical sciences ; Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; Prospective Studies ; Herpesvirus 4, Human - physiology ; Humans ; Lymphoproliferative Disorders - prevention & control ; Child, Preschool ; Rituximab ; Antibodies, Monoclonal - therapeutic use ; Male ; Transplantation, Homologous ; Viral Load ; DNA, Viral - blood ; Hematopoietic Stem Cell Transplantation - adverse effects ; Lymphocyte Count ; Female ; B-Lymphocytes - pathology ; Child ; Virus Activation ; Lymphoproliferative Disorders - etiology ; Complications and side effects ; Care and treatment ; Patient outcomes ; Epstein-Barr virus diseases ; Physiological aspects ; Development and progression ; Transplantation ; B cells ; Diagnosis ; Health aspects ; Risk factors ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2005-03, Vol.35 (S1), p.S69-S71
    Description: Pediatric experience with extracorporeal photochemotherapy (ECP) for graft-versus-host disease (GvHD) has mainly been reported by Italian and French groups. Data concerning 41 children with acute GvHD and 63 children affected by chronic GvHD are available. In 73 and 63% of them, respectively, improvement was observed, with addition of ECP to their immunosuppressive regimen. Treatment with ECP was associated with minimal side effects, even in the smallest of patients. In all responded pediatric patients, both with acute and chronic GvHD, ECP allowed progressive reduction or discontinuation of the concomitant pharmacological immunosuppressive therapy without an increase in GvHD activity. These data show that ECP is a useful therapy for children affected by GvHD resistant to conventional treatment and can be safely used.
    Subject(s): Graft vs Host Disease - therapy ; Immunosuppression - methods ; Humans ; Child, Preschool ; Female ; Infant ; Male ; Photopheresis - methods ; Child ; Care and treatment ; Graft versus host reaction ; Dosage and administration ; Diagnosis ; Photochemotherapy ; Health aspects ; Risk factors ; Immunosuppressive agents ; Cancer ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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