MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine.

The high degree of conservation in microRNA from Caenorhabditiselegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microRNA to address these changes holds significant promise. However, prostate, ovarian and breast cancers are heterogeneous and face issues of evolving therapeutic resistance. The transforming growth factor-beta (TGFβ) signaling axis plays an important role in the progression of these cancers by regulating microRNAs. Reciprocally, microRNAs regulate TGFβ actions during cancer progression. One must consider the expression of miRNA in the tumor microenvironment a source of biomarkers of disease progression and a viable target for therapeutic targeting. The differential expression pattern of microRNAs in health and disease, therapeutic response and resistance has resulted in its application as robust biomarkers. With two microRNA mimetics in ongoing restorative clinical trials, the paradigm for future clinical studies rests on the current observational trials to validate microRNA markers of disease progression. Some of today's biomarkers can be translated to the next generation of microRNA-based therapies

Trespassing the boundaries of flesh : exploring wounded embodiment through artistic practice

The aim of this paper is the contemplation of the mineness-otherness relation of being triggered by the onset of serious and chronic illness. The phenomenological theories of Frederick Svenaeus and Martin Heidegger bring to light a form of otherness (alienation) experienced with illness and allow one to question the boundaries of flesh in relation to homelessness and exile. My study is directed towards analysing this experience and finding ways of overcoming such boundaries in an effort to reach out for the suffering other through the process of empathy. The conceptual framework lies embedded in the process of reflection, relation and revelation by which the ill person encounters the self and seeks to reveal new meaning in life. Considering the body in illness as being in a state of internal war, an audio-visual tool called ‘Sanctuary’ was designed to serve the ill person’s narrative. As a mobile space that can be consumed in wards or clinics, it presents a bunker experience which magnifies one’s presence and places one’s whole body in the context of a solitary shelter whilst being assailed. The tool allows the viewer to look out onto digital artwork created as a metaphor of the self.peer-reviewe

Translation of Research Models into Clinical Practice

Abstract Many innovative techniques have been applied to address problems in medical diagnosis and healthcare delivery. Unfortunately, the vast majority of these do not make the transition into clinical practice for a number of reasons, some technical and others organizational. Technical reasons include inadequate communication between systems developers and medical professionals, limited scope of models, and user interface issues including difficulty of use and unavailability of information required by the software. Organizational issues include lack of buy-in by medical professionals and administrators, requirements for change in workflow, and resistance to technical solutions. In this article, these roadblocks are examined and a system design is presented that can begin to address a number of them

Rational decision-making in medicine: implications for overuse and underuse

open access articleIn spite of substantial spending and resource utilization, today's health care remains characterized by poor outcomes, largely due to overuse (over-testing/treatment) or underuse (under-testing/treatment) of services. To a significant extent, this is a consequence of low-quality decision-making that appears to violate various rationality criteria. Such sub-optimal decision-making is considered a leading cause of death and is responsible for more than 80% of health expenses. In this paper, we address the issue of overuse or underuse of healthcare interventions from the perspective of rational choice theory. We show that what is considered rational under one decision theory may not be considered rational under a different theory. We posit that the questions and concerns regarding both underuse and overuse have to be addressed within a specific theoretical framework. The applicable rationality criterion, and thus the “appropriateness” of health care delivery choices, depends on theory selection that is appropriate to specific clinical situations. We provide a number of illustrations showing how the choice of theoretical framework influences both our policy and individual decision-making. We also highlight the practical implications of our analysis for the current efforts to measure the quality of care and link such measurements to the financing of healthcare services

An introduction to the methods of inquiry in social sciences

Abstract. The purpose of this paper is an introduction to methods for conducting inquiries in social sciences. A method of inquiry is an organized and systematic scientific approaches used by scholars for controlled investigations and experiments to efficiently solve theoretical and practical problems, generating discoveries and/or science advances. The paper here presents, briefly, the development of models of inquiry in the philosophy of science. After that, it introduces general methods of inquiry (deduction, induction, abduction and hypothetical-deductive approaches) and specific models of scientific inquiry in social sciences, such as multiple working hypotheses. In general, modern scientific research is multifaceted and requires different approaches for generating new concepts, new hypothesis and theories. Different methods of inquiry directed to solve problems in science can be complementary approaches that foster knowledge creation within and between research fields.Keywords. Methods of inquiry, Philosophy of science, Models of inquiry, Scientific research, Conduct of inquiry.JEL. A20, A29, B40, B49

Ethics in Architecture: The Application of an Ethic of Care in the Design of a Cancer Treatment Center

The project chosen for this thesis is a healthcare facility, specifically a Cancer Treatment Center, as it is a paradigmatic project for application of an ethic of care. Moreover, healthcare facilities are not given due attention in architectural discourse and education despite the importance of their role in society. While healthcare specific organizations have begun to recognize and research the effects of built environment on health, this newfound concern seems to be generally limited to those organizations. Broader discourse involving other related professions, i.e. architecture, philosophy, psychology, sociology, etc., could benefit research as healthcare entails not only the treatment of illness, but the promotion of health. The aim of this thesis concerns the application of an ethic of care in the design of healthcare facilities, specifically, a cancer treatment center, with the intent of creating a place that emphasizes patient experience and an atmosphere or environment that is conducive to healing. It is my contention that an ethic of care may be employed as a directive in the development of design concepts, as a means to organize and create spaces in way that is better suited to the circumstance and experience of the building\u27s users

Malignant Gliomas: A Case Study

Malignant gliomas, of grade III and grade IV malignancy, are incurable neoplasms that arise from cells with several well-characterized genetic profile abnormalities that cause uncontrollable growth and infiltration in the brain. Presenting symptoms of both generalized and focal neurological abnormalities are induced by increased intracranial pressure and focal neuronal dysfunction, respectively. On average, patients experience 3 months or less of clinical history before receiving diagnosis based on multifactorial comparison of clinical and pathological presentation of the tumor. Following diagnosis, maximal safe resection and adjuvant radiotherapy and concurrent chemotherapy typically ensues with subsequent management chemotherapy regimens. Despite aggressive treatment approaches, progression or recurrence is highly typical based on 5-yr survival rates of 5.1% and 27.9% of grade IV glioblastoma multiforme (GBM) and grade III anaplastic astrocytoma (AA), respectively, the two most common malignant gliomas. Severely progressive clinical and functional deterioration in the terminal stage of care may warrant cessation of curative care replaced with maximal palliative care. Brain tumor patients experience the burden of terminal illness as other cancer patients do, but with added neurological-specific impairments that reduce quality of life. Possible causes of death include herniation, tumor progression, and systemic illness, but can be potentially multifactorial. The following manuscript characterizes the pathological mechanisms of oncogenesis and growth, followed by a comprehensive review of the clinical care for brain tumor patients from symptom onset to cause of death. To aid in the clinical applicability of these concepts, a case study of a single patient “WL”, who received a diagnosis of grade III anaplastic astrocytoma following 3 months of visual deterioration, will prompt the clinical review by illustration of disease course and treatment

Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity

SummaryWe have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with “radiation first” strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics

The Ethical Considerations of Artificial Intelligence in Clinical Decision Support

With the explosion in technological innovation facilitating the advent of artificially intelligent systems, specifically clinical decision support, a unique subset of ethical and sustainability concerns arises. Although this technology possesses remarkable potential to revolutionise the healthcare industry, it becomes apparent that an innovative ethical framework must be posited to facilitate integration into the mainstream. Due to the sensitive nature of healthcare, ethical oversights pertaining to incorporation of such technologies would lead to the detriment of its public perception, potentially stigmatising related systems for years to come. By delving into the literature surrounding the idiosyncratic ethical considerations of artificially intelligent clinical decision support in this paper, best practices which seek to mitigate the impact of these concerns emerge. The objective of this work is to assimilate these best practices, which are used in the synthesis of a six principle code of ethics which are as follows: protect healthcare professional authority, ensure technological non-maleficence, cultivate clinical decision support transparency, establish procedures for accountability determination, promote sustainability of artificially intelligence based clinical decision support and encourage equity in the training and deployment of clinical decision support. These principles are then applied to the real world of Watson for Oncology by IBM, to assess the adherence of the product to ethical and sustainability best practices