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1.
Heliyon ; 10(10): e31099, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38778973

ABSTRACT

The escalating urgency to address environmental degradation and promote sustainable development globally has emphasized the critical role of Green Finance (GF) in fostering responsible practices across industries. The tourism sector has drawn significant attention due to its substantial environmental impact, necessitating the implementation of robust financial mechanisms to mitigate its ecological footprint. China, recognized as a key player in the global tourism arena, the convergence of rapid economic expansion and the imperative for environmental conservation presents a distinctive set of challenges and opportunities. The study employed the Fuzzy Analytic Hierarchy Process (AHP) and Fuzzy Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) methodologies to systematically evaluate the impact of GF. The findings of fuzzy AHP indicate the critical role of environmental sustainability measures (GF2) as the topmost impacting factor. This refers to the practice of utilizing financial mechanisms and instruments to support initiatives that promote environmental conservation, minimize ecological footprints, and foster sustainable development. While financial allocation and effectiveness (GF1) and policy and regulatory framework impact (GF4) also hold significant importance in shaping sustainable tourism development. Moreover, the results of fuzzy TOPSIS identified top strategies such as green bond innovation for ecosystem regeneration (S1) and circular economy integration (S4), which can play a significant role in promoting sustainable tourism practices by facilitating initiatives aimed at ecosystem regeneration and integrating circular economy principles into the tourism industry.

3.
Opt Express ; 31(18): 29755-29767, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37710769

ABSTRACT

A multichannel high-dimensional data encoding/decoding scheme based on composite elliptic optical vortex (EOV) arrays is proposed. By exploiting the rotation angle of the EOV, a 4 × 4 composite EOV array is used for high-dimensional data encoding. The conjugate symmetric extension Fourier computer-generated holography algorithm with controllable reconstruction focus is used to assign different reconstruction focus to the data of the three channels (R, G, and B) of the color image. Then, the data of the three channels is transmitted simultaneously by a single hologram to further improve the transmission efficiency. At the receiver, the initial information sequence is decoded by directly identifying the captured intensity patterns with a deep learning-based convolutional neural network. In the experiment, a 128 × 128-pixel color image is successfully transmitted, which confirms the feasibility of our proposed encoding/decoding scheme. This method has great potential for future high-capacity optical communications.

4.
Opt Express ; 31(4): 5951-5962, 2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36823864

ABSTRACT

Throughout the development of single frequency fiber lasers (SFFLs), gain fiber is one of the most important components, which can greatly affect the quality of SFFLs. Here, we fabricated an Er: YAG crystal-derived silica fiber (EYDSF) using a CO2 laser-heating drawing technique, with a high gain coefficient of 1.74 dB/cm. Employing the EYDSF of only 10 cm as a gain medium, we constructed a continuous-wave ring-cavity SFFL with an all-fiber system. An ultra-narrow linewidth <660 Hz was achieved harnessing a homemade low-concentration Er-doped silica fiber as a saturable absorber. Importantly, the SFFL output power was up to 32.7 mW at 1560 nm. What's more, no multi longitudinal mode or mode hopping were found in 2 hours, and the fluctuation of power was <0.63% in 8 hours. Furthermore, the relative intensity noise was lower to -145 dB/Hz at frequencies over 1 MHz. The results indicate that the ring-cavity SFFL has desirable performance in output power, linewidth, stability and noise, which serves a prospective candidate applied to coherent optical communications, high-precision sensors, laser radars and other advanced fields.

5.
Haematologica ; 108(4): 1039-1052, 2023 04 01.
Article in English | MEDLINE | ID: mdl-35899386

ABSTRACT

The outcome of patients with acute myeloid leukemia remains poor, and immunotherapy has the potential to improve this. T cells expressing chimeric antigen receptors or bispecific T-cell engagers targeting CD123 are actively being explored in preclinical and/or early phase clinical studies. We have shown that T cells expressing CD123-specific bispecific T-cell engagers (CD123.ENG T cells) have anti-acute myeloid leukemia activity. However, like chimeric antigen receptor T cells, their effector function diminishes rapidly once they are repeatedly exposed to antigen-positive target cells. Here we sought to improve the effector function of CD123.ENG T cells by expressing inducible co-stimulatory molecules consisting of MyD88 and CD40 (iMC), MyD88 (iM), or CD40 (iC), which are activated by a chemical inducer of dimerization. CD123.ENG T cells expressing iMC, iM, or iC maintained their antigen specificity in the presence of a chemical inducer of dimerization, as judged by cytokine production (interferon-γ, interleukin-2) and their cytolytic activity. In repeat stimulation assays, activating iMC and iM, in contrast to iC, enabled CD123.ENG T cells to secrete cytokines, expand, and kill CD123-positive target cells repeatedly. Activating iMC in CD123.ENG T cells consistently improved antitumor activity in an acute myeloid leukemia xenograft model. This translated into a significant survival advantage in comparison to that of mice that received CD123.ENG or CD123.ENG.iC T cells. In contrast, activation of only iM in CD123.ENG T cells resulted in donor-dependent antitumor activity. Our work highlights the need for both toll-like receptor pathway activation via MyD88 and provision of co-stimulation via CD40 to consistently enhance the antitumor activity of CD123.ENG T cells.


Subject(s)
Leukemia, Myeloid, Acute , T-Lymphocytes , Animals , Humans , Mice , Cell Line, Tumor , Interleukin-3 Receptor alpha Subunit/metabolism , Leukemia, Myeloid, Acute/metabolism , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , T-Lymphocytes/metabolism , CD40 Antigens/metabolism
6.
Opt Express ; 30(9): 15149-15157, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35473243

ABSTRACT

To go beyond the fundamental limits imposed by latency, nonlinearity, and laser damage threshold in silica glass fibers, the hollow-core fiber (HCF) technique has been intensively investigated for decades. Recent breakthroughs in ultralow-loss HCF clearly imply that long-haul applications of HCF in communications and lasers are going to appear. Nevertheless, up to now, the HCF technique as a whole is still hampered by the limited length of a single span and the lack of HCF-based functional devices. To resolve these two issues, it is of importance to develop ultralow-loss and plug-and-play HCF interconnections. In this work, we report on HCF interconnections with the lowest-ever insertion losses (0.10 dB for HCF to standard single-mode fiber (SMF) and 0.13 dB for HCF to itself in the 1.5 µm waveband) and in a pluggable means. Two fiber mode-field adapters, one based on a graded-index multi-mode fiber (GIF) and the other utilizing a thermally expanded core (TEC) SMF, have been tested and compared. An extra insertion loss arising from imperfect refractive index distribution in a commercial GIF is observed. Our HCF interconnections also realize a back-reflection of <-35 dB over a 100 nm bandwidth as well as other critical metrics in favor of practical applications. Our technique is viable for any type of HCF.

7.
Blood Adv ; 6(21): 5737-5749, 2022 11 08.
Article in English | MEDLINE | ID: mdl-35446934

ABSTRACT

T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine release syndrome (any grade, n = 6) and neurotoxicity (any grade, n = 3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow (BM). High disease burden (≥40% morphologic blasts) before CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. After infusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells and at peak expansion, had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation (AlloHCT) had sustained, durable responses. In summary, the initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03573700.


Subject(s)
Burkitt Lymphoma , Lymphoma, B-Cell , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Humans , Antigens, CD19 , CD8-Positive T-Lymphocytes , Cost of Illness , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , T-Lymphocytes
8.
Nat Commun ; 13(1): 587, 2022 01 31.
Article in English | MEDLINE | ID: mdl-35102167

ABSTRACT

Developing CAR T cells for acute myeloid leukemia (AML) has been hampered by a paucity of targets that are expressed on AML blasts and not on hematopoietic progenitor cells (HPCs). Here we demonstrate that GRP78 is expressed on the cell surface of primary AML blasts but not HPCs. To target GRP78, we generate T cell expressing a GRP78-specific peptide-based CAR, which show evidence of minimal fratricide post activation/transduction and antigen-dependent T cell differentiation. GRP78-CAR T cells recognize and kill GRP78-positive AML cells without toxicity to HPCs. In vivo, GRP78-CAR T cells have significant anti-AML activity. To prevent antigen-dependent T cell differentiation, we block CAR signaling and GRP78 cell surface expression post activation by using dasatinib during GRP78-CAR T cell manufacturing. This significantly improves their effector function in vitro and in vivo. Thus, targeting cell surface GRP78-positive AML with CAR T cells is feasible, and warrants further active exploration.


Subject(s)
Cell Membrane/metabolism , Endoplasmic Reticulum Chaperone BiP/immunology , Hematopoietic Stem Cells/immunology , Leukemia, Myeloid, Acute/immunology , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/immunology , Animals , Cell Line, Tumor , Cell Membrane/drug effects , Cell Survival/drug effects , Cytokines/metabolism , Cytotoxicity, Immunologic/drug effects , Dasatinib/pharmacology , Gene Expression Regulation, Leukemic/drug effects , Humans , Leukemia, Myeloid, Acute/genetics , Mice, Inbred NOD , Mice, SCID , T-Lymphocytes/drug effects , Xenograft Model Antitumor Assays
9.
Transplant Cell Ther ; 28(5): 262.e1-262.e10, 2022 05.
Article in English | MEDLINE | ID: mdl-35151936

ABSTRACT

Pediatric patients with high-risk hematologic malignancies who experience relapse after a prior allogeneic hematopoietic cell transplant (HCT) have an exceedingly poor prognosis. A second allogeneic HCT offers the potential for long-term cure but carries high risks of both subsequent relapse and HCT-related morbidity and mortality. Using haploidentical donors for HCT (haploHCT) can expand the donor pool and potentially enhance the graft-versus-leukemia effect but is accompanied by a risk of graft-versus-host disease (GVHD). The goal of this protocol was to intensify the antileukemia effect of haploHCT for pediatric patients with hematologic malignancies that relapsed after prior allogeneic HCT, while limiting regimen-associated toxicities. This phase II clinical trial evaluated a sub-myeloablative preparative regimen consisting of anti-thymocyte globulin, clofarabine, cytarabine, busulfan, and cyclophosphamide, in combination with plerixafor to sensitize leukemic blasts. Participants received a mobilized peripheral blood unmanipulated haploidentical donor graft with one dose of post-transplant cyclophosphamide as GVHD prophylaxis, followed by natural killer (NK) cell addback. Here we report the clinical outcomes and immune reconstitution of 17 participants treated on the study and 5 additional patients treated on similar single-patient treatment plans. Of the 22 participants analyzed, 12 (55%) had active disease at the time of HCT. The regimen provided robust immune reconstitution, with 21 participants (95%) experiencing neutrophil engraftment at a median of 14 days after HCT. In this high-risk population, the overall survival was 45% (95% confidence interval [CI], 24%-64%), with a 12-month event-free survival of 31% (95% CI, 14%-51%) and cumulative incidence of relapse at 12 months of 50% (95% CI, 27%-69%). Four participants (18%) remain in remission at >5 years follow-up. Expected HCT-related organ-specific toxicities were observed, and 13 participants (59%) experienced acute or chronic GVHD. This intensified but sub-myeloablative regimen, followed by a high-dose unmanipulated haploidentical graft, post-transplantation cyclophosphamide, and NK cell infusion, resulted in adequate immune reconstitution but failed to overcome the elevated risks of relapse and treatment-related morbidity in this high-risk population.


Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Child , Cyclophosphamide/therapeutic use , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Heterocyclic Compounds , Humans , Recurrence
10.
Transplant Cell Ther ; 28(2): 73.e1-73.e9, 2022 02.
Article in English | MEDLINE | ID: mdl-34875402

ABSTRACT

CD19-specific chimeric antigen receptor (CAR) T-cell therapies, including the FDA-approved tisagenlecleucel, induce high rates of remission in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, post-treatment relapse remains an issue. Optimal management of B-ALL after tisagenlecleucel treatment remains elusive, and continued tracking of outcomes is necessary to establish a standard of care for this population. We sought to evaluate outcomes on the real-world use of tisagenlecleucel in a contemporary pediatric patient population and to identify risk factors influencing event-free survival (EFS) and overall survival (OS). Additionally, we aimed to describe post-tisagenlecleucel management strategies, including use of allogeneic hematopoietic cell transplantation (AlloHCT) or repeat CAR T-cell infusions. We report on 31 pediatric and adolescent and young adult patients (AYA) with B-ALL, treated with lymphodepleting chemotherapy followed by tisagenlecleucel. Patients were treated at Johns Hopkins Hospital and St. Jude Children's Research Hospital between March 2018 and November 2020. Data on patient, disease, and treatment characteristics were collected retrospectively from medical records and described. EFS and OS were estimated by the Kaplan-Meier method and compared by the log-rank test. Single-factor and multiple-factor analysis of EFS and OS were performed by fitting Cox regression models. Of the 30 evaluable patients, 25 (83.3%) experienced a complete response, with 21 having negative minimal residual disease. Treatment was well tolerated, with expected rates of cytokine release syndrome (61.3%) and immune effector cell-associated neurotoxicity (29%). After initial complete response, 12 patients (48%) had subsequent disease recurrence, with CD19-negative relapse (n = 6) occurring sooner than CD19-positive relapse (P = .0125). With a median follow-up time of 386 days (range 11-1187 days), the EFS for the entire cohort (n = 31) at 6 and 12 months after infusion was 47% (95% confidence interval [CI], 28.4%-63.4%) and 35.2% (95% CI, 18.4%-52.5%), respectively. In multivariate analysis, high pretreatment leukemic burden (≥5% bone marrow blasts) was an independent risk factor for inferior EFS (HR 5.98 [95% CI, 1.1-32.4], P = .0380) and OS (HR 4.2 [95% CI, 1.33-13.39], P = .0148). Tisagenlecleucel induced high initial response rates in a contemporary cohort of pediatric and AYA patients with B-ALL. However, 48% of patients experienced subsequent disease relapse, including 6 with antigen-escape variants. This highlights a considerable limitation of single-agent autologous CD19-CAR T-cell therapy. Pretreatment leukemic disease burden of ≥5% blasts was significantly associated with worse outcomes in this study, including lower EFS and OS. Our findings suggest that reducing preinfusion leukemic burden is a viable treatment strategy to improve outcomes of CAR T-cell therapy.


Subject(s)
Burkitt Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Adolescent , Antigens, CD19/therapeutic use , Child , Cost of Illness , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell , Receptors, Chimeric Antigen/therapeutic use , Recurrence , Retrospective Studies , Young Adult
11.
Cancer ; 128(3): 606-614, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34643950

ABSTRACT

BACKGROUND: Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study examined the prevalence of and risk factors for primary hypothyroidism and its associations with physical, neurocognitive, and psychosocial outcomes. METHODS: This was a retrospective study with a cross-sectional health outcome analysis of an established cohort comprising 2965 survivors of childhood cancer (52.8% male; median current age, 30.9 years, median time since cancer diagnosis, 22.3 years). Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between primary hypothyroidism and cancer-related risk factors, cardiovascular disease risk factors, frailty, neurocognitive and QOL outcomes, social attainment, and subsequent thyroid carcinoma. Associations between serum free thyroxine and thyrotropin levels at assessment and health outcomes were explored. RESULTS: The prevalence of primary hypothyroidism was 14.7% (95% CI, 13.5%-16.0%). It was more likely in females (OR, 1.06; 95% CI, 1.03-1.08), was less likely in non-Whites (OR, 0.96; 95% CI, 0.93-0.99), was associated with thyroid radiotherapy (higher risk at higher doses), and was more common if cancer was diagnosed at an age ≥ 15.0 years versus an age < 5 years (OR, 1.05; 95% CI, 1.01-1.09). Primary hypothyroidism was associated with frailty (OR, 1.54; 95% CI, 1.05-2.26), dyslipidemia (OR, 1.52; 95% CI, 1.14-2.04), impaired physical QOL (OR, 1.66; 95% CI, 1.12-2.48), and having health care insurance (OR, 1.51; 95% CI, 1.07-2.12). CONCLUSIONS: Primary hypothyroidism is common in survivors and is associated with unfavorable physical health and QOL outcomes. The impact of thyroid hormone replacement practices on these outcomes should be investigated further.


Subject(s)
Cancer Survivors , Hypothyroidism , Leukemia, Myeloid, Acute , Adolescent , Adult , Cancer Survivors/psychology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Hypothyroidism/epidemiology , Leukemia, Myeloid, Acute/complications , Male , Prevalence , Quality of Life , Retrospective Studies , Risk Factors
12.
Bone Marrow Transplant ; 56(12): 2997-3007, 2021 12.
Article in English | MEDLINE | ID: mdl-34480120

ABSTRACT

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Child , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/complications , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation Conditioning/adverse effects
13.
Bone Marrow Transplant ; 56(8): 1866-1875, 2021 08.
Article in English | MEDLINE | ID: mdl-33742153

ABSTRACT

Disease relapse remains a major cause of treatment failure in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for high-risk acute leukemias or myelodysplastic syndromes (MDS). Comprehensive data on outcomes after post-transplant relapse are lacking, especially in pediatric patients. Our objective was to assess the impact of various transplant-, patient-, and disease-related variables on survival and outcomes in patients who relapse after alloHCT. We describe our institutional experience with 221 pediatric patients who experienced disease relapse after their first alloHCT for acute leukemias or MDS between 1990 and 2018. In a multivariable model, being in first complete remission at first alloHCT, longer duration of remission after alloHCT, experiencing GVHD and receiving a transplant in a more recent time period were significantly associated with a higher likelihood of receiving a second alloHCT after post-transplant relapse. Of these variables, only longer interval from alloHCT to relapse, receiving a second alloHCT or DLI, and receiving a transplant in a more recent time period were associated with improved overall survival. Our data support pursuing second alloHCT for patients who have experienced relapse after their first transplant, as that remains the only salvage modality with a reasonable chance of inducing long-term remission.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Acute Disease , Humans , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Recurrence
14.
Front Oncol ; 10: 584269, 2020.
Article in English | MEDLINE | ID: mdl-33163412

ABSTRACT

Introduction: Respiratory complications due to engraftment syndrome (ES) in the post-hematopoietic stem cell transplant (HSCT) setting can lead to acute respiratory failure (ARF). Outcomes of children developing ARF due to engraftment are unknown. Methods: We conducted a retrospective analysis of 1,527 pediatric HSCT recipients and identified children who developed ARF due to ES over a 17-year period. Thirty patients that developed ARF and required invasive mechanical ventilation (IMV) due to ES were included in this study. Results: The survival rate for our cohort was 80% [alive at intensive care unit (ICU) discharge]. The most common underlying primary disease was hematologic malignancy, and 67% of children underwent allogeneic HSCT. Further, 73% required vasopressor drips and 23% underwent dialysis. Survivors had a shorter median ICU length of stay than did non-survivors (15 vs. 40 days, respectively, p = 0.01). Survivors had a significantly lower median cumulative fluid overload % on days 4 and 5 after initiation of IMV than did non-survivors (2.8 vs. 14.0 ml/kg, p = 0.038 on day 4, and 1.8 vs. 14.9 ml/kg, p = 0.044 on day 5, respectively). Conclusion: Our results suggest that children who develop ARF during engraftment have better ICU survival rates than do those with other etiologies of ARF post-HSCT. Furthermore, fluid overload contributes to mortality in these children; therefore, strategies to prevent and address fluid overload should be considered.

15.
J Opt Soc Am A Opt Image Sci Vis ; 37(9): 1448-1455, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32902435

ABSTRACT

Recently, a new form of laser beam, called the "centrosymmetric optical vortex" (CSOV), has been proposed. We employ the modified calculation method for studying the propagation of the CSOV beam, which is constructed via four canonical optical vortices with different topological charges. The speed of calculation is more convenient and faster than the usual means by using the diffraction integral directly. With a modified calculation method, the propagation properties of the CSOV in free space are illustrated and analyzed using numerical examples. Several parameters influencing the CSOV beams and the ABCD optical system are discussed in detail. Our experimental results are consistent with theoretical predictions. Furthermore, the orbital angular momentum states and density are also studied. The research results are expected to provide a basis for the application of CSOV beams in beam reshaping, optical trapping, and rotating microparticle manipulation, particularly in separating cells.

16.
Opt Express ; 28(16): 23771-23783, 2020 Aug 03.
Article in English | MEDLINE | ID: mdl-32752369

ABSTRACT

We fabricated a Yb-doped yttrium aluminium garnet (Yb:YAG) crystal-derived silica fiber (YCDSF) using an assembly consisting of a YAG crystal rod and silica tube on a CO2 laser-heated drawing tower. The fiber has a Yb concentration of 5.66 wt%, and absorption coefficient of 32 dB/cm at 980 nm. The figure of merit of the unsaturated absorption and gain per unit length of the YCDSF are 93% and 4.4 dB/cm, respectively. Based on the results of the numerical simulation, an all-fiber distributed Bragg reflector (DBR) laser using only a 1.5-cm-long YCDSF is experimentally demonstrated to have a maximum output power of 360 mW with a pump threshold power of 21 mW. The fiber laser also achieved an optical signal-to-noise ratio of 80 dB, a beam quality factor of 1.022 in two orthogonal directions and a slope efficiency of up to 50.5%. These results indicate that the all-fiber DBR laser has potential applications in high-quality seed sources and coherent optical communications.

17.
Bone Marrow Transplant ; 55(7): 1357-1366, 2020 07.
Article in English | MEDLINE | ID: mdl-32273588

ABSTRACT

Pediatric, adolescent, and young adult patients with relapsed or refractory Hodgkin lymphoma receive multimodal therapy, including autologous hematopoietic cell transplantation (AutoHCT). Despite aggressive therapy, historical outcomes for this patient population have been poor. This paper describes a single institutional experience utilizing AutoHCT in 74 patients treated from 1988-2015. Our results demonstrate significantly improved outcomes over time. Compared with patients treated in the earlier era (1988-2001), 5-year overall survival improved from 62.5 ± 9.6% to 91.8 ± 4.4% (p < 0.001) and event free survival improved from 41.7 ± 9.6% to 87.7 ± 5.3% (I < 0.001) for patients treated in a later era (2002-2015). Improvements in survival are multifactorial, including reductions in both relapse and nonrelapse mortality. Further investigation is needed to determine the role of AutoHCT in a modern treatment cohort that includes frequent use of targeted immunotherapies. In addition, as the use and availability of effective novel therapeutics increases for this patient population there may be an opportunity for the reduction of standard cytotoxic therapies, including in AutoHCT preparative regimens, thereby mitigating late effects.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Hodgkin Disease/drug therapy , Humans , Neoplasm Recurrence, Local/therapy , Recurrence , Transplantation, Autologous , Treatment Outcome , Young Adult
18.
Blood ; 135(21): 1847-1858, 2020 05 21.
Article in English | MEDLINE | ID: mdl-32243495

ABSTRACT

Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT.


Subject(s)
Cancer Survivors/statistics & numerical data , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Patient Reported Outcome Measures , Quality of Life , Adolescent , Adult , Aged , Case-Control Studies , Child , Chronic Disease , Cross-Sectional Studies , Female , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Risk Factors , Surveys and Questionnaires , Young Adult
19.
Cancer ; 126(6): 1330-1338, 2020 03 15.
Article in English | MEDLINE | ID: mdl-31923330

ABSTRACT

BACKGROUND: The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma. METHODS: Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity. RESULTS: By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5). CONCLUSIONS: Because of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors.


Subject(s)
Cancer Survivors/statistics & numerical data , Neuroblastoma/complications , Quality of Life , Adult , Anxiety/epidemiology , Cancer Survivors/psychology , Chronic Disease/epidemiology , Confidence Intervals , Female , Hearing Loss/chemically induced , Hearing Loss/epidemiology , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , Hypertriglyceridemia/epidemiology , Independent Living/statistics & numerical data , Male , Marriage/statistics & numerical data , Middle Aged , Nervous System Diseases/epidemiology , Neuroblastoma/psychology , Obesity/epidemiology , Outcome Assessment, Health Care , Pain/epidemiology , Psychological Distress , Social Class , Somatoform Disorders/epidemiology , Unemployment/statistics & numerical data , Young Adult
20.
J Opt Soc Am A Opt Image Sci Vis ; 35(9): 1585-1591, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30183014

ABSTRACT

Hybridly polarized Laguerre-Gaussian vector beams (HPLGVBs) with zero radial index are obtained based on the third type of Laguerre-Gaussian vector beams. Polarization distributions of HPLGVBs are controlled by the phase retardation of a wave plate. The ellipticity angle and polarization orientation angle are used to describe the polarization distributions of the HPLGVBs. The electric field intensity distributions of tightly focused HPLGVBs are analyzed in the focal plane by the Richards-Wolf vectorial diffraction method. It is found that the tightly focused HPLGVBs have a focal shift phenomenon. The dependence of the focal shift of the HPLGVBs on the different parameters is discussed in detail. The simulation results show that the magnitude of the focal shift is related to the polarization distribution, and the focal shift is quite obvious for large azimuthal mode index, long focal length, large numerical aperture, and narrow beam waist. The effective control of the focal shift will have great potential applications in optical micromanipulation.

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