This dissertation details Design Science Research that examines the design, development, and deployment of a mobile social media application for a higher education institution. Social capital in ...higher education “commuter” institutions may be decreasing because fewer students stay on campus. Social capital is defined as a network of relationships in a group. Higher social capital is derived from more complex and broader networks. Social networks can grow because individuals who belong to a particular group have a sense of community. If students spend less time on campus their sense of community, or the feeling that one is part of a social structure, may decrease because they are less likely to participate in the network. This puts higher education “commuter” institutions at an immediate disadvantage in terms of generating social capital. It may be possible, however, to combat this disadvantage by actively promoting participating in an online social network. Specifically, my research project focuses on the use of a recommender system in an online social network to determine the effects a mobile application that uses recommendations has on a scholarly community: How does it affect the sense of community amongst the users of an online social network? How does it affect the level of social capital in an alumni community? How does it affect the ability of students and alumni to harness the social capital that exists in their social network? This dissertation suggests that introducing a purposefully-designed online social network has the potential to facilitate creation of structural and relational social capital. The design artifact is for iOS mobile devices. It was coded from the ground up in Objective C, using a Parse framework for data storage, push notifications, and analytics. The app uses a recommender system via push notifications to connect users with similar or complimentary skills or research interests. The design artifact’s validity was tested through a series of 5 focus groups consisting of 28 current students and alumni from a graduate university setting who used the artifact for different tasks during the focus group sessions. Results show that users responded positively to the design artifact and its constructs, and that it has potential to increase structural and relational social capital in a higher education setting, but that might not have an effect on cognitive social capital.
•Outcomes of patients treated with venetoclax-based nonintensive therapies across >50 NHS hospitals mirror those seen in clinical trials.•Current mutation based prognostic systems are inadequate; ...collaborative efforts are needed to establish a definitive prognostic scheme.
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Venetoclax with azacitidine is the standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy; however, uncertainties remain regarding the treatment schedule, accurate prognostication, and outcomes for patients treated outside clinical trials. The option of venetoclax with low-dose cytarabine (LDAC) is also available; however, it is not clear for which patients it may be a useful alternative. Here, we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n = 587) or LDAC (n = 67). The median age was 73 years, and 59% had de novo AML. Most patients received 100 mg of venetoclax with an azole antifungal. In cycle 1, patients spent a median of 14 days in the hospital, and 85% required red cell transfusion, 59% platelet transfusion, and 63% required IV antibiotics. Supportive care requirements significantly reduced after the first cycle. Patients receiving venetoclax-azacitidine had a complete remission (CR)/CR with incomplete hematological recovery rate of 67%, day 30 and day 60 mortality of 5% and 8%, respectively, and median overall survival of 13.6 months. Mutations in NPM1, RUNX1, STAG2, and IDH2 were associated with improved survival, whereas age, secondary and therapy-related AML, +8, MECOM rearrangements, complex karyotype, ASXL1, and KIT mutations were associated with poorer survival. Prognostic systems derived specifically for patients treated with venetoclax-azacitidine performed better than the European LeukemiaNet and Medical Research Council classifications; however, improved risk classifications are still required. In the 149 patients with NPM1 mutated AML, outcomes were similar for those treated with venetoclax-azacitidine and venetoclax-LDAC.
The use of peripheral blood progenitor cell (PBPC) transplantation is an important advance in the treatment of breast cancer and acute leukaemias, and these conditions are among the commonest ...indications for this procedure. Inevitably, there is concern that malignant cells may contaminate progenitor cell harvests and be re-infused during transplantation and cause disease relapse. Various methods are available for the detection of such minimal residual disease (MRD), and the key aim of this project was to evaluate the feasibility of using a tumour-specific marker, namely mutations within the p53 gene, for this purpose. This provided a useful model to assess the feasibility of using subtle genetic changes to detect MRD within PBPC harvests from patients with malignant diseases. The first step involved the use of denaturing gradient gel electrophoresis (DGGE) to screen original tumour tissues for mutations to be used as disease markers, in 5 individually PCR-amplified DNA fragments (A to E) covering exons 5 to 8 of p53. The technique was first optimised using cell lines known to contain p53 mutations in each fragment. Optimisation was performed with respect to electrophoresis temperature, time, voltage and polyacrylamide cross-linker. The sensitivity of DGGE in detecting a mutation in a mixed cell population was determined by diluting tumour cells in wild type (WT) cells. Although the presence of a mutation could be demonstrated when tumour cells occurred as 5% of total, a representation of at least 40% was required for the mutant homoduplex to be isolated for sequencing. Clinical samples studied were from 51 breast cancer patients, 38 of whom had metastatic disease or at high risk of metastasis, and 13 had high risk stage II/III disease randomised in a clinical study investigating PBPC transplantation and adjuvant therapy, and from 29 patients with acute leukaemias. A positive result was obtained in 14 of 51 primary breast cancer patients (1 was positive in 2 different fragments) and 3 of 29 patients with acute leukaemias.
The use of peripheral blood progenitor cell (PBPC) transplantation is an important advance in the treatment of breast cancer and acute leukaemias, and these conditions are among the commonest ...indications for this procedure. Inevitably, there is concern that malignant cells may contaminate progenitor cell harvests and be re-infused during transplantation and cause disease relapse. Various methods are available for the detection of such minimal residual disease (MRD), and the key aim of this project was to evaluate the feasibility of using a tumour-specific marker, namely mutations within the p53 gene, for this purpose. This provided a useful model to assess the feasibility of using subtle genetic changes to detect MRD within PBPC harvests from patients with malignant diseases. The first step involved the use of denaturing gradient gel electrophoresis (DGGE) to screen original tumour tissues for mutations to be used as disease markers, in 5 individually PCR-amplified DNA fragments (A to E) covering exons 5 to 8 of p53. The technique was first optimised using cell lines known to contain p53 mutations in each fragment. Optimisation was performed with respect to electrophoresis temperature, time, voltage and polyacrylamide cross-linker. The sensitivity of DGGE in detecting a mutation in a mixed cell population was determined by diluting tumour cells in wild type (WT) cells. Although the presence of a mutation could be demonstrated when tumour cells occurred as 5% of total, a representation of at least 40% was required for the mutant homoduplex to be isolated for sequencing. Clinical samples studied were from 51 breast cancer patients, 38 of whom had metastatic disease or at high risk of metastasis, and 13 had high risk stage II/III disease randomised in a clinical study investigating PBPC transplantation and adjuvant therapy, and from 29 patients with acute leukaemias. A positive result was obtained in 14 of 51 primary breast cancer patients (1 was positive in 2 different fragments) and 3 of 29 patients with acute leukaemias.
This study describes the design and implementation of an online intellectual community that targeted only the School of Information Systems and Technology (SISAT) at CGU, and the steps taken to ...foster active participation amongst community members. The artifact developed was an online community for the purpose of improving the sense of community amongst students, faculty, and alumni of SISAT by allowing community members to exchange ideas and experience. We found that in order to motivate active participation in a system such as ours, we required a strong administrative presence to provide content and implementing effective interventions on a regular basis to sustain user interest and generate motivation to engage in active participation.
Pain and Depression: A Systematic Review IsHak, Waguih William; Wen, Raymond Y; Naghdechi, Lancer ...
Harvard review of psychiatry,
11/2018, Letnik:
26, Številka:
6
Journal Article
Recenzirano
Pain comorbid with depression is frequently encountered in clinical settings and often leads to significant impaired functioning. Given the complexity of comorbidities, it is important to address ...both pain and depressive symptoms when evaluating treatment options.
To review studies addressing pain comorbid with depression, and to report the impact of current treatments.
A systematic search of the literature databases was conducted according to predefined criteria. Two authors independently conducted a focused analysis of the full-text articles and reached a consensus on 28 articles to be included in this review.
Overall, studies suggested that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. These symptoms could lead to poor physical functional outcomes and longer duration of symptoms. An important biochemical basis for pain and depression focuses on serotonergic and norepinephrine systems, which is evident in the pain-ameliorating properties of serotonergic and norepinephrine antidepressants. Alternative pharmacotherapies such as ketamine and cannabinoids appear to be safe and effective options for improving depressive symptoms and ameliorating pain. In addition, cognitive-behavioral therapy may be a promising tool in the management of chronic pain and depression.
The majority of the literature indicates that patients with pain and depression experience reduced physical, mental, and social functioning as opposed to patients with only depression or only pain. In addition, ketamine, psychotropic, and cognitive-behavioral therapies present promising options for treating both pain and depression.
E-cigarettes vaporize propylene glycol/vegetable glycerin (PG/VG), nicotine, and flavorings. However, the long-term health effects of exposing lungs to vaped e-liquids are unknown.
To determine the ...effects of chronic vaping on pulmonary epithelia.
We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers) and obtained bronchial brush biopsies and lavage samples from these subjects for proteomic investigation. We further employed in vitro and murine exposure models to support our human findings.
Visual inspection by bronchoscopy revealed that vaper airways appeared friable and erythematous. Epithelial cells from biopsy samples revealed approximately 300 proteins that were differentially expressed in smoker and vaper airways, with only 78 proteins being commonly altered in both groups and 113 uniquely altered in vapers. For example, CYP1B1 (cytochrome P450 family 1 subfamily B member 1), MUC5AC (mucin 5 AC), and MUC4 levels were increased in vapers. Aerosolized PG/VG alone significantly increased MUC5AC protein in human airway epithelial cultures and in murine nasal epithelia in vivo. We also found that e-liquids rapidly entered cells and that PG/VG reduced membrane fluidity and impaired protein diffusion.
We conclude that chronic vaping exerts marked biological effects on the lung and that these effects may in part be mediated by the PG/VG base. These changes are likely not harmless and may have clinical implications for the development of chronic lung disease. Further studies will be required to determine the full extent of vaping on the lung.
Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased ...mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl(-) and Na(+) epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%-65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.
Humans are one of the few species undergoing an adolescent growth spurt. Because children enter the spurt at different ages making age a poor maturity measure, longitudinal studies are necessary to ...identify the growth patterns and identify commonalities in adolescent growth. The standard maturity determinant, peak height velocity (PHV) timing, is difficult to estimate in individuals due to diurnal, postural, and measurement variation. Using prospective longitudinal populations of healthy children from two North American populations, we compared the timing of the adolescent growth spurt's peak height velocity to normalized heights and hand skeletal maturity radiographs. We found that in healthy children, the adolescent growth spurt is standardized at 90% of final height with similar patterns for children of both sexes beginning at the initiation of the growth spurt. Once children enter the growth spurt, their growth pattern is consistent between children with peak growth at 90% of final height and skeletal maturity closely reflecting growth remaining. This ability to use 90% of final height as easily identified important maturity standard with its close relationship to skeletal maturity represents a significant advance allowing accurate prediction of future growth for individual children and accurate maturity comparisons for future studies of children's growth.
Congenital disorders of glycosylation (CDG) and Niemann‐Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile‐onset severe liver disease and other ...multisystemic manifestations. Plasma bile acid and N‐palmitoyl‐O‐phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1‐CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N‐(3β,5α,6β‐trihydroxy‐cholan‐24‐oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1‐, ALG1‐, ALG8‐, and PMM2‐CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.
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