12,720 research outputs found
Die akute Appendizitis im Kindes- und Jugendalter: neue diagnostische Verfahren für die prätherapeutische Differenzierung histopathologischer Entitäten zur Unterstützung konservativer Therapiestrategien
Hintergrund der hier zusammengefassten Studien war die aktuelle Datenlage, die dafür spricht, dass es sich bei der klinisch unkomplizierten, histopathologisch phlegmonösen und der klinisch komplizierten, histopathologisch gangränösen Appendizitis um unabhängige Entitäten handelt. Diese können unterschiedlichen Therapieoptionen (konservativ vs. operativ) zugeführt werden. Vor diesem Hintergrund war es ein Ziel der Arbeiten zu untersuchen, wie die Formen der akuten Appendizitis im Kindes- und Jugendalter bereits prätherapeutisch unterschieden werden können.
Sowohl in der Labordiagnostik (P1 und P2) als auch im Ultraschall (P3) lassen sich Unterschiede zwischen Patient*innen mit unkomplizierter, phlegmonöser und komplizierter (gangränöser und perforierender) Appendizitis aufzeigen. Hierdurch allein kann allerdings aufgrund unzureichender Trennschärfe noch keine ausreichende Entscheidungssicherheit erreicht werden. Mit Verfahren der künstlichen Intelligenz auf Untersucher-unabhängige diagnostische Parameter (P4) konnte die Vorhersagegenauigkeit der akuten Appendizitis weiter gesteigert werden. Interessante Ergebnisse bezüglich der unterschiedlichen Pathomechanismen der beiden inflammatorischen Entitäten ergaben sich durch eine differenzielle Genexpressionsanalyse (P5). In einer Proof-of-Concept-Studie wurden zuvor beschriebene Methoden der künstlichen Intelligenz auf die Genexpressionsdaten angewandt (P6). Hierdurch konnte im Modell eine grundsätzliche Differenzierbarkeit der Entitäten durch die Anwendung der neuen Methode aufgezeigt werden.
Ein mittelfristiges Ziel ist es, eine Biomarkersignatur zu definieren, die ihre Aussagekraft durch einen Computeralgorithmus hat. Hierdurch soll eine schnelle Therapieentscheidung ermöglicht werden. Im Idealfall sollte diese Biomarkersignatur sicher, objektiv und einfach zu bestimmen sein sowie eine höhere diagnostische Sicherheit als die bisherige Diagnostik mittels Anamnese, Untersuchung, Laboranalyse und Ultraschall bieten.
Langfristiges Ziel von Folgestudien ist die Identifizierung einer Biomarkersignatur mit der bestmöglichen Vorhersagekraft. Hinsichtlich der routinemäßigen klinischen Diagnostik ist die Anwendung von Point-of-Care Devices auf PCR-Basis denkbar. Hier könnte eine limitierte Anzahl von Primern für eine Biomarkersignatur mit hoher Vorhersagekraft zum Einsatz kommen. Der dadurch ermittelte Biomarker würde seine Aussagekraft durch einen einfach anzuwendenden Computeralgorithmus erhalten. Die Kombination aus Genexpressionsanalyse mit Methoden der künstlichen Intelligenz kann somit die Grundlage für ein neues diagnostisches Instrument zur sicheren Unterscheidung unterschiedlicher Appendizitisentitäten darstellen
In vitro investigation of the effect of disulfiram on hypoxia induced NFκB, epithelial to mesenchymal transition and cancer stem cells in glioblastoma cell lines
A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.Glioblastoma multiforme (GBM) is one of the most aggressive and lethal cancers with a poor prognosis. Advances in the treatment of GBM are limited due to several resistance mechanisms and limited drug delivery into the central nervous system (CNS) compartment by the blood-brain barrier (BBB) and by actions of the normal brain to counteract tumour-targeting medications. Hypoxia is common in malignant brain tumours such as GBM and plays a significant role in tumour pathobiology. It is widely accepted that hypoxia is a major driver of GBM malignancy. Although it has been confirmed that hypoxia induces GBM stem-like-cells (GSCs), which are highly invasive and resistant to all chemotherapeutic agents, the detailed molecular pathways linking hypoxia, GSC traits and chemoresistance remain obscure. Evidence shows that hypoxia induces cancer stem cell phenotypes via epithelial-to-mesenchymal transition (EMT), promoting therapeutic resistance in most cancers, including GBM.
This study demonstrated that spheroid cultured GBM cells consist of a large population of hypoxic cells with CSC and EMT characteristics. GSCs are chemo-resistant and displayed increased levels of HIFs and NFκB activity. Similarly, the hypoxia cultured GBM cells manifested GSC traits, chemoresistance and invasiveness. These results suggest that hypoxia is responsible for GBM stemness, chemoresistance and invasiveness. GBM cells transfected with nuclear factor kappa B-p65 (NFκB-p65) subunit exhibited CSC and EMT markers indicating the essential role of NFκB in maintaining GSC phenotypes. The study also highlighted the significance of NFκB in driving chemoresistance, invasiveness, and the potential role of NFκB as the central regulator of hypoxia-induced stemness in GBM cells. GSC population has the ability of self-renewal, cancer initiation and development of secondary heterogeneous cancer. The very poor prognosis of GBM could largely be attributed to the existence of GSCs, which promote tumour propagation, maintenance, radio- and chemoresistance and local infiltration.
In this study, we used Disulfiram (DS), a drug used for more than 65 years in alcoholism clinics, in combination with copper (Cu) to target the NFκB pathway, reverse chemoresistance and block invasion in GSCs. The obtained results showed that DS/Cu is highly cytotoxic to GBM cells and completely eradicated the resistant CSC population at low dose levels in vitro. DS/Cu inhibited the migration and invasion of hypoxia-induced CSC and EMT like GBM cells at low nanomolar concentrations.
DS is an FDA approved drug with low toxicity to normal tissues and can pass through the BBB. Further research may lead to the quick translation of DS into cancer clinics and provide new therapeutic options to improve treatment outcomes in GBM patients
Organizations decentered: data objects, technology and knowledge
Data are no longer simply a component of administrative and managerial work but a pervasive resource and medium through which organizations come to know and act upon the contingencies they confront. We theorize how the ongoing technological developments reinforce the traditional functions of data as instruments of management and control but also reframe and extend their role. By rendering data as technical entities, digital technologies transform the process of knowing and the knowledge functions data fulfil in socioeconomic life. These functions are most of the times mediated by putting together disperse and steadily updatable data in more stable entities we refer to as data objects. Users, customers, products, and physical machines rendered as data objects become the technical and cognitive means through which organizational knowledge, patterns, and practices develop. Such conditions loosen the dependence of data from domain knowledge, reorder the relative significance of internal versus external references in organizations, and contribute to a paradigmatic contemporary development that we identify with the decentering of organizations of which digital platforms are an important specimen
Investigating and mitigating the role of neutralisation techniques on information security policies violation in healthcare organisations
Healthcare organisations today rely heavily on Electronic Medical Records systems (EMRs), which have become highly crucial IT assets that require significant security efforts to safeguard patients’ information. Individuals who have legitimate access to an organisation’s assets to perform their day-to-day duties but intentionally or unintentionally violate information security policies can jeopardise their organisation’s information security efforts and cause significant legal and financial losses. In the information security (InfoSec) literature, several studies emphasised the necessity to understand why employees behave in ways that contradict information security requirements but have offered widely different solutions. In an effort to respond to this situation, this thesis addressed the gap in the information security academic research by providing a deep understanding of the problem of medical practitioners’ behavioural justifications to violate information security policies and then determining proper solutions to reduce this undesirable behaviour. Neutralisation theory was used as the theoretical basis for the research. This thesis adopted a mixed-method research approach that comprises four consecutive phases, and each phase represents a research study that was conducted in light of the results from the preceding phase. The first phase of the thesis started by investigating the relationship between medical practitioners’ neutralisation techniques and their intention to violate information security policies that protect a patient’s privacy. A quantitative study was conducted to extend the work of Siponen and Vance [1] through a study of the Saudi Arabia healthcare industry. The data was collected via an online questionnaire from 66 Medical Interns (MIs) working in four academic hospitals. The study found that six neutralisation techniques—(1) appeal to higher loyalties, (2) defence of necessity, (3) the metaphor of ledger, (4) denial of responsibility, (5) denial of injury, and (6) condemnation of condemners—significantly contribute to the justifications of the MIs in hypothetically violating information security policies. The second phase of this research used a series of semi-structured interviews with IT security professionals in one of the largest academic hospitals in Saudi Arabia to explore the environmental factors that motivated the medical practitioners to evoke various neutralisation techniques. The results revealed that social, organisational, and emotional factors all stimulated the behavioural justifications to breach information security policies. During these interviews, it became clear that the IT department needed to ensure that security policies fit the daily tasks of the medical practitioners by providing alternative solutions to ensure the effectiveness of those policies. Based on these interviews, the objective of the following two phases was to improve the effectiveness of InfoSec policies against the use of behavioural justification by engaging the end users in the modification of existing policies via a collaborative writing process. Those two phases were conducted in the UK and Saudi Arabia to determine whether the collaborative writing process could produce a more effective security policy that balanced the security requirements with daily business needs, thus leading to a reduction in the use of neutralisation techniques to violate security policies. The overall result confirmed that the involvement of the end users via a collaborative writing process positively improved the effectiveness of the security policy to mitigate the individual behavioural justifications, showing that the process is a promising one to enhance security compliance
Statistical Learning for Gene Expression Biomarker Detection in Neurodegenerative Diseases
In this work, statistical learning approaches are used to detect biomarkers for neurodegenerative diseases (NDs). NDs are becoming increasingly prevalent as populations age, making understanding of disease and identification of biomarkers progressively important for facilitating early diagnosis and the screening of individuals for clinical trials. Advancements in gene expression profiling has enabled the exploration of disease biomarkers at an unprecedented scale. The work presented here demonstrates the value of gene expression data in understanding the underlying processes and detection of biomarkers of NDs. The value of novel approaches to previously collected -omics data is shown and it is demonstrated that new therapeutic targets can be identified. Additionally, the importance of meta-analysis to improve power of multiple small studies is demonstrated. The value of blood transcriptomics data is shown in applications to researching NDs to understand underlying processes using network analysis and a novel hub detection method. Finally, after demonstrating the value of blood gene expression data for investigating NDs, a combination of feature selection and classification algorithms were used to identify novel accurate biomarker signatures for the diagnosis and prognosis of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Additionally, the use of feature pools based on previous knowledge of disease and the viability of neural networks in dimensionality reduction and biomarker detection is demonstrated and discussed. In summary, gene expression data is shown to be valuable for the investigation of ND and novel gene biomarker signatures for the diagnosis and prognosis of PD and AD
AIUCD 2022 - Proceedings
L’undicesima edizione del Convegno Nazionale dell’AIUCD-Associazione di Informatica Umanistica ha per titolo Culture digitali. Intersezioni: filosofia, arti, media. Nel titolo è presente, in maniera esplicita, la richiesta di una riflessione, metodologica e teorica, sull’interrelazione tra tecnologie digitali, scienze dell’informazione, discipline filosofiche, mondo delle arti e cultural studies
La gestión de la reputación online en las asociaciones españolas de enfermos de cáncer: una propuesta de modelo
Cancer patients’ associations have become valid public health players because they help patients to face this disease from physical, emotional and social perspectives. Some of these associations resort to social media platforms not only to improve their relationships with patients, but also to promote their own brand. This paper seeks to understand how Spanish cancer patients’ associations manage their social media platforms to promote their brand. To do that, we conducted a literature review about health communication; we considered 48 indicators to analyze how 107 associations belonging to the Spanish Group of Cancer Patients (Gepac) managed Facebook, Twitter, Youtube and their corporate website for branding initiatives; and we proposed a communication model for branding cancer patients’ associations on these platforms (MedPac Model). We concluded that Spanish cancer patients’ associations prioritize medical information but not brand-related elements, they lack the economic and human resources to produce a quality content, and they have not yet implemented a true corporate communication approach.Las asociaciones de enfermos de cáncer se han convertido en un verdadero actor de salud pública ya que ayudan a los pacientes a afrontar esta enfermedad desde un punto de vista fÃsico, emocional y social. Algunas de estas asociaciones recurren a las redes sociales para mejorar sus relaciones con los pacientes, asà como para promocionar su propia marca. Este artÃculo tiene como objetivo comprender cómo las asociaciones españolas de pacientes con cáncer gestionan sus redes sociales para promover su marca. Para ello, realizamos una revisión de literatura sobre comunicación en salud; recurrimos a 48 indicadores para analizar cómo las 107 asociaciones pertenecientes al Grupo Español de Enfermos de Cáncer (Gepac) gestionaban Facebook, Twitter, Youtube y su web corporativa para promocionar su marca; y finalmente proponemos un modelo de comunicación para ayudar a dichas asociaciones a promocionar su marca en las redes sociales (Modelo MedPac). Concluimos que las asociaciones españolas de enfermos de cáncer priorizan la información médica pero no la arquitectura de marca, carecen de los recursos económicos y humanos necesarios para producir contenidos de calidad, y no implementan un verdadero enfoque de comunicación corporativa
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The Contingent Role of Conflict: Deliberative Interaction and Disagreement in Shareholder Engagement
How is the tension between conflict and deliberation resolved in shareholder engagement? We address this question by studying shareholder engagement as a deliberative process with three stages: establishing dialogue, solution development, and solution implementation. We theorize that two interactionist mechanisms, deliberative interaction and the voicing of disagreement, play different roles at different stages of the process. We test our hypotheses with a proprietary database of 169 environmental, social and governance (ESG) engagements with US public companies over 2007–2012. We find that while deliberative interaction does not help advance the engagement process, it positively moderates the effect of disagreement in the solution-development stage. By contrast, in the solution-implementation stage, deliberative interaction amplifies the negative effect of disagreement, thus hindering progress in the engagement. Our paper contributes to shareholder engagement, deliberation theory and interactionist organization theory by establishing that engagement effectiveness is an interactional achievement, shaped by both deliberation and disagreement
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