539 research outputs found

    An Integrative Framework for Contextual Factors Affecting Information Technology Implementation

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    While previous research has provided a great deal of information on individual factors that play a role in IT implementation success, a gap in the research exists when it comes to formulating a holistic view of overall environmental factors. This paper conducts a literature review and expands Weill’s conversion effectiveness model to develop a framework integrating the various enterprise-level contextual factors affecting IT implementation. It also discusses relationships among contextual factors and cross-border issues in the global outsourcing environment. This holistic interpretation of individual factors is an initial step toward understanding the complexities of corporate environments and their effects on IT implementation success. The framework can provide companies with a useful tool to evaluate their current environment, determine its strengths and weaknesses, and assess how these will affect IT implementation

    Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab

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    We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma in order to define markers of activity in the blood and tumor as assessed at baseline (before ipilimumab) and early on-treatment. Patients were treated with ipilimumab (10 mg/kg intravenously every 3 weeks x2 doses) bracketing surgery. Tumor and blood biospecimens were obtained at baseline and at surgery. Flow cytometry and immunohistochemistry for select biomarkers were performed. Thirty five patients were enrolled; IIIB (3; N2b), IIIC (32; N2c, N3), IV (2). Worst toxicities included Grade 3 diarrhea/colitis (5; 14%), hepatitis (2; 6%), rash (1; 3%), elevated lipase (3; 9%). Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS) was 11 months, 95% CI (6.2-19.2). There was a significant decrease in circulating myeloid derived suppressor cells (MDSC). Greater decrease in circulating monocyte gate MDSC Lin1-/HLA-DR-/CD33+/CD11b+ was associated with improved PFS (p = 0.03). There was a significant increase in circulating regulatory T cells (Treg; CD4+CD25hi+Foxp3+) that, unexpectedly, was associated with improved PFS (HR = 0.57; p = 0.034). Baseline evidence of fully activated type I CD4+ and CD8+ antigen-specific T cell immunity against cancer-testis (NY-ESO-1) and melanocytic lineage (MART-1, gp100) antigens was detected and was significantly potentiated after ipilimumab. In tumor, there was a significant increase in CD8+ T cells after ipilimumab (p = 0.02). Ipilimumab induced increased tumor infiltration by fully activated (CD69+) CD3+/CD4+ and CD3 +/CD8+ T cells with evidence of induction/potentiation of memory T cells (CD45RO+). The change in Treg observed within the tumor showed an inverse relationship with clinical benefit and greater decrease in tumor MDSC subset Lin1-/HLA-DR-/CD33+/CD11b+ was associated with improved PFS at one year. Neoadjuvant evaluation revealed a significant immunomodulating role for ipilimumab on Treg, MDSC and effector T cells in the circulation and tumor microenvironment that warrants further pursuit in the quest for optimizing melanoma immunotherapy. © 2014 Tarhini et al

    The Precision of the Human Hand: Variability in Pinch Strength and Manual Dexterity

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    Changes in hand morphology throughout human evolution have facilitated the use of forceful pad-to-pad precision grips, contributing to the development of fine motor movement and dexterous manipulation typical of modern humans. Today, variation in human hand function may be affected by demographic and/or lifestyle factors, but these remain largely unexplored. We measured pinch grip strength and dexterity in a heterogeneous cross-sectional sample of human participants (n = 556) to test for the potential effects of sex, age, hand asymmetries, hand morphology, and frequently practiced manual activities across the lifespan. We found a significant effect of sex on pinch strength, dexterity, and different directional asymmetries, with the practice of manual musical instruments, significantly increasing female dexterity for both hands. Males and females with wider hands were also stronger, but not more precise, than those with longer hands, while the thumb-index ratio had no effect. Hand dominance asymmetry further had a significant effect on dexterity but not on pinch strength. These results indicate that different patterns of hand asymmetries and hand function are influenced in part by life experiences, improving our understanding of the link between hand form and function and offering a referential context for interpreting the evolution of human dexterity

    Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

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    Background: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. Methods: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. Results and Discussion: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-γ Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines. © 2007 Okada et al; licensee BioMed Central Ltd

    The zoogeomorphology of case‐building caddisfly: Quantifying sediment use

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    Caddisfly (Trichoptera) larvae are an abundant and widespread aquatic insect group characterised by the construction of silk structures, including nets and cases. Case‐building caddisfly have the potential to modify the sorting and mobility of sand and fine gravel via; 1) case construction, resulting in altered sediment properties; 2) transporting sediment incorporated into cases over the river bed and; 3) changing the structure of river‐beds via burrowing. To investigate these mechanisms, it is necessary to understand the mass, size distribution and spatial variability of sediment use by case‐building caddisfly larvae.We quantified the mineral sediment used by individuals and communities of case‐building caddisfly in 27 samples, from three sites on a gravel‐bed stream. The mass and size distribution of sediment in individual cases varied between taxa (mass = 0.001 – 0.83 g, D50 = 0.17 – 4 mm). The mean mass of sediment used by the caddisfly community was 38 g m‐2 and varied locally. Sediment use was predominantly coarse sand (D50 = 1 mm). 64% of sediment use was attributable to Agapetus fuscipes (Glossosomatidae).Due to within‐species variability in case mass, the abundance of most taxa, including A. fuscipes, was only weakly associated with the mass of sediment used at the river scale. Whilst the caddisfly community used a small percentage of the total sediment available (average 2.99% of the 1‐1.4 mm size fraction), A. fuscipes used more fine sediment in their cases at sites where it was more available. Despite variability in local habitat, all sites supported diverse case‐building caddisfly communities utilising mineral sediment. Consequently, geomorphological effects of case‐building caddisfly are potentially widespread. The results provide novel insights into the specific grain sizes and quantities of fine sediment particles (g m‐2) used by caddisfly larvae, which represents an important step towards understanding their zoogeomorphic activities

    Increased Vascularity in Cervicovaginal Mucosa with Schistosoma haematobium Infection

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    Schistosomiasis is a fresh water parasite infection that affects millions of people, especially in Africa. Recent knowledge about the genital manifestations of schistosomiasis; especially its possible association with human immunodeficiency virus (HIV) infection, has led to increased focus on this neglected tropical disease. Millions of women remain undiagnosed for genital schistosomiasis, and may suffer from abnormal mucosal blood vessels, contact bleeding and lesions named sandy patches. This study analyses a unique selection of female genital biopsies containing parasite eggs. Protein detection and standard histopathological assessment are combined to quantify and study the characteristics of the mucosal blood vessels surrounding the eggs. Our results show that the genital mucosa with parasite eggs is more vascularised compared to healthy tissue, and that viable eggs tend to be surrounded by proliferating blood vessels. These findings have not yet been correlated directly to clinical manifestations. Further studies are needed in order to provide clinical advice on the risks and consequences of mucosal lesions particular to female genital schistosomiasis

    Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania

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    BACKGROUND: Schistosomiasis affects the reproductive health of women. Described sequelae are ectopic pregnancy, infertility, abortion, and cervical lesions and symptoms mimicking cervical cancer and STIs. There are indications that cervical schistosomiasis lesions could become co-factors for viral infection such as HIV and HPV. METHODS: In a retrospective descriptive histopathological study clinical specimens sent between 1999 and 2005 to the pathology department of a consultant hospital in Tanzania were reviewed to analyse the occurrence and features of schistosomiasis in female genital organs. RESULTS: During the study period, schistosomiasis was histopathologically diagnosed in 423 specimens from different organs (0.7% of all specimens examined in the study period), out of those 40% were specimens from female and male organs. The specimens were sent from 24 hospitals in 13 regions of mainland Tanzania. Female genital schistosomiasis was diagnosed in 125 specimens from 111 patients. The main symptoms reported were bleeding disorders (48%), ulcer (17%), tumor (20%), lower abdominal pain (11%) and infertility (7%). The majority of cases with genital schistosomiasis were diagnosed in cervical tissue (71 cases). The confirmation of cervical cancer was specifically requested for 53 women, but the diagnosis could only be verified for 13 patients (25%), in 40 cases only severe cervical schistosomiasis was diagnosed. Vulval/labial schistosomiasis was seen in specimens from young women. Infertility was reported in four patients with schistosomiasis of the Fallopian tubes. CONCLUSION: Genital schistosomiasis adds to the disease burden of women in all age groups. Pathological consequences due to the involvement of different genital organs can be damaging for the affected women. Clinical unawareness of genital schistosomiasis can lead to misdiagnosis and therefore false and ineffective therapy. In endemic areas cervical schistosomiasis should be considered as differential diagnosis of cancer

    Nutritional care of medical inpatients: a health technology assessment

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    BACKGROUND: The inspiration for the present assessment of the nutritional care of medical patients is puzzlement about the divide that exists between the theoretical knowledge about the importance of the diet for ill persons, and the common failure to incorporate nutritional aspects in the treatment and care of the patients. The purpose is to clarify existing problems in the nutritional care of Danish medical inpatients, to elucidate how the nutritional care for these inpatients can be improved, and to analyse the costs of this improvement. METHODS: Qualitative and quantitative methods are deployed to outline how nutritional care of medical inpatients is performed at three Danish hospitals. The practices observed are compared with official recommendations for nutritional care of inpatients. Factors extraneous and counterproductive to optimal nutritional care are identified from the perspectives of patients and professional staff. A review of the literature illustrates the potential for optimal nutritional care. A health economic analysis is performed to elucidate the savings potential of improved nutritional care. RESULTS: The prospects for improvements in nutritional care are ameliorated if hospital management clearly identifies nutritional care as a priority area, and enjoys access to management tools for quality assurance. The prospects are also improved if a committed professional at the ward has the necessary time resources to perform nutritional care in practice, and if the care staff can requisition patient meals rich in nutrients 24 hours a day. At the kitchen production level prospects benefit from a facilitator contact between care and kitchen staff, and if the kitchen staff controls the whole food path from the kitchen to the patient. At the patient level, prospects are improved if patients receive information about the choice of food and drink, and have a better nutrition dialogue with the care staff. Better nutritional care of medical patients in Denmark is estimated to hold a cost savings potential reaching approximately USD 22 million. CONCLUSION: Every hospital and every bed ward has its strengths and weaknesses, but none of the participating bed wards fully satisfy nutritional care success criteria. All organisational levels have a significant potential for improvements of nutritional care of medical inpatients

    Characteristics of undernourished older medical patients and the identification of predictors for undernutrition status

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    <p>Abstract</p> <p>Background</p> <p>Undernutrition among older people is a continuing source of concern, particularly among acutely hospitalized patients. The purpose of the current study is to compare malnourished elderly patients with those at nutritional risk and identify factors contributing to the variability between the groups.</p> <p>Methods</p> <p>The study was carried out at the Soroka University Medical Center in the south of Israel. From September 2003 through December 2004, all patients 65 years-of-age or older admitted to any of the internal medicine departments, were screened within 72 hours of admission to determine nutritional status using the short version of the Mini Nutritional Assessment (MNA-SF). Patients at nutritional risk were entered the study and were divided into malnourished or 'at risk' based on the full version of the MNA. Data regarding medical, nutritional, functional, and emotional status were obtained by trained interviewers.</p> <p>Results</p> <p>Two hundred fifty-nine elderly patients, 43.6% men, participated in the study; 18.5% were identified as malnourished and 81.5% were at risk for malnutrition according to the MNA. The malnourished group was less educated, had a higher depression score and lower cognitive and physical functioning. Higher prevalence of chewing problems, nausea, and vomiting was detected among malnourished patients. There was no difference between the groups in health status indicators except for subjective health evaluation which was poorer among the malnourished group. Lower dietary score indicating lower intake of vegetables fruits and fluid, poor appetite and difficulties in eating distinguished between malnourished and at-risk populations with the highest sensitivity and specificity as compare with the anthropometric, global, and self-assessment of nutritional status parts of the MNA. In a multivariate analysis, lower cognitive function, education <12 years and chewing problems were all risk factors for malnutrition.</p> <p>Conclusion</p> <p>Our study indicates that low food consumption as well as poor appetite and chewing problems are associated with the development of malnutrition. Given the critical importance of nutritional status in the hospitalized elderly, further intervention trials are required to determine the best intervention strategies to overcome these problems.</p
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