| 1. |
- Zahid, Nida
(författare)
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Risk factors and late effects of primary brain tumor in children and young people treated at tertiary care hospitals of Karachi, Pakistan
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite significant advancements, primary brain tumors (PBTs) sadly remains a major cause of morbidity and mortality, especially among children and young people (CYP) worldwide.Aims: This study aimed to evaluate the risk factors and late effects of PBTs among CYP and their primary caregivers at tertiary care hospitals in Karachi, Pakistan.Method: Study 1 was a matched case-control study at a private tertiary care hospital. Telephonic interviews were conducted with mothers of 122 cases (CYP with PBTs, ages 5-21) and 122 controls (CYP without tumors, ages 5-21) treated between 2017 and 2022. Conditional logistic regression was used for data analysis with STATA software version 12. Studies II to IV were prospective cohort studies conducted at private and public tertiary care hospitals. Forty-eight CYP with PBTs and their primary caregivers were recruited. CYP were assessed pre-treatment and at 12 months post-treatment for neurocognitive outcomes using validated tools such as the Slosson Intelligence Tool, Raven's Progressive Matrices, and Wechsler Intelligence Scale. Quality of life (QoL) of CYP and their caregivers were evaluated using the Pediatric Quality of Life Inventory. Generalized estimating equations were used for data analysis with STATA software version 12. Study V was a pilot exploratory study. The microRNA expression was assessed using quantitative polymerase chain reaction (qPCR). Data was analyzed by R software.Results: The risk factors of PBTs among CYP were maternal analgesic use, paternal addictive substance use (specially smoking), higher household income, and lower paternal education. Predictors of neurocognitive outcomes in CYP were tumor type, surgical resection, post-treatment seizures, lower socioeconomic status, and low maternal education. Predictors of QoL in CYP were hydrocephalous managed with shunt and/or EVD and surgical resection. Factors affecting the QoL and family functioning of primary caregivers (mothers) included CYPs having post-treatment seizures, CYP's cognition and QoL scores, and financial burden of the disease. A significant correlation was found between pre-treatment miRNA-210 and miRNA-10b with non-verbal neurocognition at 12 months post-treatment. Conclusions: The study identified sociodemographic and antenatal risk factors associated with PBTs in CYP. It also highlighted the factors impacting the neurocognitive outcomes in CYP and QoL outcomes in CYP and their mothers. Understanding these predictors can guide the development of cost-effective treatments aimed at reducing the neurocognitive and psychological burdens faced by CYP and their primary caregivers. Future research should focus on larger-scale, multi-country studies to ensure broader applicability and generalizability of the findings.
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| 2. |
- Mårtensson, Thomas
(författare)
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Acute gastrointestinal graft-versus-host disease in allogeneic hematopoietic stem cell transplanted children and adolescents : clinical aspects of histopathological evaluation and risk factors
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute graft-versus-host disease (aGVHD), following allogeneic hematopoietic stem cell transplantation (HSCT), is a potentially life-threating condition. Gastrointestinal involvement of aGVHD (GI-aGVHD) affects approximately every fourth transplanted child. The diagnosis of GI-aGVHD is primarily symptom-based. However, symptoms associated with GI-aGVHD are nonspecific; thus, histopathological confirmation of the diagnosis, is recommended. The overall objectives of this thesis were: i) to evaluate the influence of two different conditioning regimens on the incidence of GI-aGVHD, and ii) to evaluate clinical aspects of the currently recommended diagnostic approach to GI-aGVHD, i.e., endoscopy-guided histopathological assessment, applied to pediatric HSCT patients. Patients and methods: Four retrospective cohort studies were included in this thesis. Paper I enrolled all children with HSCT performed during 2000–2010 at Karolinska University Hospital Huddinge who also had underlying diagnoses of juvenile myelomonocytic leukemia (JMML) or myelodysplastic syndrome (MDS). The children were conditioned with busulfan (Bu) and cyclophosphamide (Cy), with or without addition of melphalan (Mel). Paper IIIV included all children who underwent HSCT at any of the four HSCT centers in Sweden between 2000 and 2012 and with endoscopy-guided histopathological assessment performed to confirm symptom-based GI-aGVHD within one-year post-HSCT. In paper III-IV a retrospective, blinded, histopathological assessment (RIHA) was carried out based on the National Institutes of Health (NIH) 2014 criteria for histopathology-based GI-GVHD. Paper IV only included those with at least a biopsy sampling from the rectosigmoid area and the area proximal to the left colonic flexure. Results: Paper I. Twenty-five children were enrolled. Forty-seven percent (8/17) of the children that received addition of Mel to the BuCy conditioning, versus none (0/8) in the BuCy group, developed GI-aGVHD (stages 2-4) (p<0.05). Paper II. Based on 68 children with 91 endoscopic occasions, treatment changes in response to histopathology reports occurred in 48% (44/91). Paper III. Seventy children with 92 endoscopic occasions were assessed. Histopathologybased GI-GVHD diagnosis was established in 67 of 92 (73%) endoscopic occasions in the RIHA and in 50 of 92 (54%) in the clinical standard histopathological assessment (p=0.014). The risk of a subsequent re-endoscopy within one-year post-HSCT was higher in endoscopic occasions with GI-GVHD solely detected in RIHA versus non-GI-GVHD in both assessments (p=0.005). Paper IV. Forty-four children with 51 endoscopic occasions were analyzed. Biopsies from the rectosigmoid area had 85% sensitivity for RIHA-based GI-GVHD diagnosis. The corresponding figure for combined biopsy sampling from both rectosigmoid area and upper gastrointestinal tract was 97% and was similarly high compared with biopsies collected from complete lower endoscopy. Conclusions: I) Addition of Mel to the BuCy conditioning increased the incidence of symptom-based GI-aGVHD in children with JMML and MDS. II) Endoscopy-guided histopathological assessment was found to influence the treatment decisions and should therefore be considered in children with GI-aGVHD. III) In children with symptom-based GI-aGVHD, without confirmation of the diagnosis by clinical standard histopathological assessment, a second histopathological assessment based on the NIH 2014 criteria should be considered before performing a re-endoscopy. IV) Sigmoidoscopy combined with upper endoscopy, colonoscopy/ileocolonoscopy, or full upper and lower endoscopy should be considered as preferred choices for the endoscopic procedure in children with clinically suspected GI-aGVHD.
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| 3. |
- Mårtensson, Thomas
(författare)
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Semiconductor Nanowires: Epitaxy and Applications
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Semiconductor nanowires are nanoscale objects formed by bottom-up synthesis. In recent years their unique properties have been exploited in fields such as electronics, photonics, sensors and the life sciences. In this work, the epitaxial growth of nanowires and their applications were studied. Heteroepitaxial growth of III-V nanowires on silicon substrates was demonstrated. This may enable direct band gap materials for optoelectronic devices, as well as high-mobility, low-contact resistance materials for electronics, to be integrated directly on the Si platform. Furthermore, gold-free nanowire synthesis on Si was demonstrated, which offers an advantage in terms of compatibility with established Si processing. Controlled nanowire synthesis by employing lithography was demonstrated. This combination of established "top-down" planar processing, and "bottom-up" nanowire growth, enables deterministic synthesis with individual nanowire site control. The process was first demonstrated with electron beam lithography and later extended to nanoimprint lithography, which is a parallel, high-throughput method, suitable for commercial volumes. Nanowire applications were demonstrated by three examples: (i) Vertical light-emitting diodes (LEDs) based on GaAs/InGaP core/shell nanowires, epitaxially grown on GaP and Si substrates. LED functionality was established on both kinds of substrates. This provided a direct demonstration of light-emitting devices on Si made possible by heteroepitaxial III-V nanowire growth on Si. (ii) A single-electron transistor constructed from a heterostructured nanowire with an InAs island sandwiched between two InP barriers. The narrow diameter of the nanowire provides the lateral confinement, and the tunnel barrier resistances are tunable by varying the InP barrier thickness. Coulomb oscillations and Coulomb blockade with a charging energy of approx. 4 meV were observed. (iii) Sensory nerve cell interactions with nanowires. Substrates covered with 2.5 um long and 50 nm diameter nanowires supported cell adhesion and axonal outgrowth. The cells interacted closely with the nanostructures, and viable cells penetrated by wires were observed, as well as wire bending due to forces exerted by the cells.
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