Immunoediting and angiogenesis in ovarian cancer

Advances in the treatment of ovarian cancer have had a limited impact on prognosis over recent decades. Alternatives to the traditional surgical and chemotherapeutic approach are being sought. Many novel therapies relate to a greater understanding of the molecular changes which occur during carcinogenesis and the development of targeted therapies to exploit these abnormalities. The aim of this thesis was to investigate the prognostic significance of markers relating to tumour immunology, angiogenesis and apoptosis, through the use of Tissue Microarray Technology. 339 cases of ovarian cancers diagnosed between 1982 and 1997 were assessed. Tumours were analysed immunohistochemically for expression of components of the IFNy (IFNGR1, STAT1, p27, caspase 1), TRAIL (DR4 and DR5) and angiogenic (VEGF) pathways. Loss of expression of IFNGR1 was an independent predictor of poor prognosis, although STAT 1 was not. High levels of cytoplasmic and nuclear p27 expression were associated with a reduced survival; cytoplasmic was independently prognostic. Tumours with reduced levels of caspase 1 had improved survival. These results suggest that only patients expressing IFNGR1 may benefit from IFNy therapy and provides evidence of immunoediting in ovarian cancer. DR4 and DR5 did not predict prognosis suggesting that the TRAIL pathway may not be significant in ovarian cancer apoptosis with implications for TRAIL-related therapy. High levels of VEGF occurred infrequently, being an independent marker of poor prognosis. This may identify a group of patients who may preferentially benefit from anti-angiogenic therapy. The thesis illustrates that ovarian cancers are heterogeneous and variations in expression of protein markers can predict tumour behaviour and stratify for therapy. Future targeted therapies may be selected on the basis of an immunohistochemical profile which predicts the pathways that are still functioning. New therapies as they arise should be trialed and targeted to tumours expressing the appropriate molecular markers

Immunoediting and angiogenesis in ovarian cancer

Advances in the treatment of ovarian cancer have had a limited impact on prognosis over recent decades. Alternatives to the traditional surgical and chemotherapeutic approach are being sought. Many novel therapies relate to a greater understanding of the molecular changes which occur during carcinogenesis and the development of targeted therapies to exploit these abnormalities. The aim of this thesis was to investigate the prognostic significance of markers relating to tumour immunology, angiogenesis and apoptosis, through the use of Tissue Microarray Technology. 339 cases of ovarian cancers diagnosed between 1982 and 1997 were assessed. Tumours were analysed immunohistochemically for expression of components of the IFNy (IFNGR1, STAT1, p27, caspase 1), TRAIL (DR4 and DR5) and angiogenic (VEGF) pathways. Loss of expression of IFNGR1 was an independent predictor of poor prognosis, although STAT 1 was not. High levels of cytoplasmic and nuclear p27 expression were associated with a reduced survival; cytoplasmic was independently prognostic. Tumours with reduced levels of caspase 1 had improved survival. These results suggest that only patients expressing IFNGR1 may benefit from IFNy therapy and provides evidence of immunoediting in ovarian cancer. DR4 and DR5 did not predict prognosis suggesting that the TRAIL pathway may not be significant in ovarian cancer apoptosis with implications for TRAIL-related therapy. High levels of VEGF occurred infrequently, being an independent marker of poor prognosis. This may identify a group of patients who may preferentially benefit from anti-angiogenic therapy. The thesis illustrates that ovarian cancers are heterogeneous and variations in expression of protein markers can predict tumour behaviour and stratify for therapy. Future targeted therapies may be selected on the basis of an immunohistochemical profile which predicts the pathways that are still functioning. New therapies as they arise should be trialed and targeted to tumours expressing the appropriate molecular markers

Understanding patient needs and gaps in radiology reports through online discussion forum analysis

Our objective is to investigate patient needs and understand information gaps in radiology reports using patient questions that were posted on online discussion forums. We leveraged online question and answer platforms to collect questions posted by patients to understand current gaps and patient needs. We retrieved six hundred fifty-nine (659) questions using the following sites: Yahoo Answers, Reddit.com, Quora, and Wiki Answers. The questions retrieved were analyzed and the major themes and topics were identified. The questions retrieved were classified into eight major themes. The themes were related to the following topics: radiology report, safety, price, preparation, procedure, meaning, medical staff, and patient portal. Among the 659 questions, 35.50% were concerned with the radiology report. The most common question topics in the radiology report focused on patient understanding of the radiology report (62 of 234 [26.49%]), image visualization (53 of 234 [22.64%]), and report representation (46 of 234 [19.65%]). We also found that most patients were concerned about understanding the MRI report (32%; n = 143) compared with the other imaging modalities (n = 434). Using online discussion forums, we discussed major unmet patient needs and information gaps in radiology reports. These issues could be improved to enhance radiology design in the future

Washeteria closures, infectious disease and community health in rural Alaska: a review of clinical data in Kivalina, Alaska

Background. Kivalina is a northwest Alaska barrier island village of 400 people vulnerable to storm surges exacerbated recently by delayed winter sea and shore ice formation. The village has no in-home piped water or sewage; the “washeteria” is the only structure providing public showers, laundry facilities and flush toilets. In October 2004, a storm damaged the washeteria septic system resulting in prolonged facility closures. We assessed rates of gastrointestinal, respiratory and skin infections potentially impacted by prolonged washeteria closures. Methods. We obtained washeteria closure dates from 2003 to July 2009 and defined >7 day closure as prolonged. We received de-identified data on all Kivalina clinic visits from 2003 to 2009 and selected visits with ICD-9 diagnosis codes for respiratory, skin, or gastrointestinal infection; subsequent same patient/same illness-category visits within 14 days were excluded. We compared annual visit rates, for all ages combined, before (2003–2004) and after (2005–2009) the “2004” storm. Results. The washeteria had prolonged closures for 34 days (4.7%) in the 2 years 2003–2004 and 864 days (51.7%) between January 2005 and July 2009. Closures ranged from 8 to 248 days. Respiratory infection rates declined significantly from 1.32 visits/person/year in the 2003–2004 period to 0.99 visits/person/year in the 2005–2009 period. There was a significant increase in skin infection rates after 2004, peaking at 0.28 visits/person/year in 2007 and then declining significantly to 0.15 visits/person/year in 2009. Gastrointestinal infection rates remained stable and low throughout (average: 0.05 visits/person/year). No temporal association was observed between respiratory, gastrointestinal or skin infection rates and prolonged washeteria closures. Conclusion. The Kivalina washeteria was closed frequently and for extended periods between 2005 and 2009. Initial closures possibly resulted in increased skin infection rates. No increase in respiratory or gastrointestinal infections was noted. Evaluation of community adaptations to closures and other factors (e.g. childhood pneumococcal vaccination) would expand understanding of these findings

Efficiency of TTAC's ORTEC IDM

ORNL's Technical Testing and Analysis Center (TTAC) acquired a High Purity Germanium Detector (HPGe) from ORTEC - a variant called an Interchangeable Detection Module (IDM). This detector has excellent energy resolution as well as high intrinsic efficiency. The purpose of this report is to detail the determination of the efficiency curve of the IDM, so future measurements can quantify the (otherwise unknown) activity of sources. Without such a curve, the activity cannot be directly reported by use of the IDM alone - a separate device such as an ion chamber would be required. This builds upon the capability of TTAC. The method for determining the energy-dependent intrinsic efficiency is laid-out in this report. It's noteworthy that this basic technique can be applied to any spectroscopic radiation detector, independent of the specific type (e.g. NaI, CzT, ClYC)

"Super Gene Set" Causal Relationship Discovery from Functional Genomics Data

In this article, we present a computational framework to identify "causal relationships" among super gene sets. For "causal relationships," we refer to both stimulatory and inhibitory regulatory relationships, regardless of through direct or indirect mechanisms. For super gene sets, we refer to "pathways, annotated lists, and gene signatures," or PAGs. To identify causal relationships among PAGs, we extend the previous work on identifying PAG-to-PAG regulatory relationships by further requiring them to be significantly enriched with gene-to-gene co-expression pairs across the two PAGs involved. This is achieved by developing a quantitative metric based on PAG-to-PAG Co-expressions (PPC), which we use to infer the likelihood that PAG-to-PAG relationships under examination are causal-either stimulatory or inhibitory. Since true causal relationships are unknown, we approximate the overall performance of inferring causal relationships with the performance of recalling known r-type PAG-to-PAG relationships from causal PAG-to-PAG inference, using a functional genomics benchmark dataset from the GEO database. We report the area-under-curve (AUC) performance for both precision and recall being 0.81. By applying our framework to a myeloid-derived suppressor cells (MDSC) dataset, we further demonstrate that this framework is effective in helping build multi-scale biomolecular systems models with new insights on regulatory and causal links for downstream biological interpretations

Wireless Bus Interconnects for Small Satellite Systems

For small satellite engineering systems, successfully managing the hundreds of in-system interconnections caused by a wired interface is a major element in the success of a SmallSat mission. Testing, integration, and mission operation of SmallSat subsystems frequently requires system interfaces to be reconfigured for extended mission capability and system reliability. We propose a Bluetooth Low Energy (BLE) based wireless interface technology to enable post-deployment reconfiguration of in-system interfaces. This wireless inter-face will improve system reliability while enabling ad hoc system level changes and reducing the probability of subsystem failure. While a wireless interconnect brings many benefits, its implementation raises potential technical challenges, including additional power consumption, data latency, interference with ground communications, susceptibility, and emissions. This work presents the concepts of wireless interface technologies, proof-of-concept experimental results of a BLE-based wireless interface system, and analysis of effective solutions for the aforementioned technical challenges. By limiting the RF power of the wireless interfaces, the susceptibility, emissions, and power consumption were be made minimal. Latency and interference were also be minimized through software optimization and error correction techniques. Proof-of-concept prototype lab experiments demonstrate the feasibility and adaptability of the proposed technology with increased ability to reconfigure assets compared to traditional wire-based interconnects

“Lessons that simply cannot be lectured”: Highlighting the experiences and benefits of undergraduates engaged in community psychology research

Globally, Community Psychology (CP) currently struggles with a lack of visibility and a shortage of platforms from which to engage future researchers and practitioners. Many of these future researchers and practitioners study psychology as part of their undergraduate education, making psychology departments in undergraduate institutions an ideal point of exposure. Discouragingly, however, undergraduate students are unlikely to be exposed to CP in their course curriculums forcing students to seek out opportunities for exposure elsewhere (Jimenez, 2016; Glantsman, McMahon & Njoku et al., 2015). This is especially true of Community Psychology within the United States. This study aimed to explore how students got involved in CP research and the benefits of that involvement. A total of 34 former undergraduate research assistants involved in CP research teams at Michigan State University completed a 20-item online questionnaire comprised of open- and closed-ended questions. Quantitative data were analyzed descriptively and qualitative data were analyzed using an iterative coding process. Results showed that the majority of students had no experience in CP and merely stumbled upon the research. Despite this, respondents reported gaining many skills, competencies, and knowledge during their time on the research teams. Respondents particularly benefited from: 1) gaining hands-on and community-based research skills; 2) attaining transferable skills they could carry with them in future positions; 3) acquiring CP-specific competencies; and 4) cultivating greater awareness and passion for social issues. Finally, the majority of respondents discussed how their involvement on CP research teams honed in their interest and passions and/or shaped their professional trajectory.  These findings provide preliminary evidence of the benefits of CP research involvement at an undergraduate level and has important implications for how CP as a field may choose to invest in undergraduate research opportunities.&nbsp

“Lessons that simply cannot be lectured”: Highlighting the experiences and benefits of undergraduates engaged in community psychology research

Globally, Community Psychology (CP) currently struggles with a lack of visibility and a shortage of platforms from which to engage future researchers and practitioners. Many of these future researchers and practitioners study psychology as part of their undergraduate education, making psychology departments in undergraduate institutions an ideal point of exposure. Discouragingly, however, undergraduate students are unlikely to be exposed to CP in their course curriculums forcing students to seek out opportunities for exposure elsewhere (Jimenez, 2016; Glantsman, McMahon & Njoku et al., 2015). This is especially true of Community Psychology within the United States. This study aimed to explore how students got involved in CP research and the benefits of that involvement. A total of 34 former undergraduate research assistants involved in CP research teams at Michigan State University completed a 20-item online questionnaire comprised of open- and closed-ended questions. Quantitative data were analyzed descriptively and qualitative data were analyzed using an iterative coding process. Results showed that the majority of students had no experience in CP and merely stumbled upon the research. Despite this, respondents reported gaining many skills, competencies, and knowledge during their time on the research teams. Respondents particularly benefited from: 1) gaining hands-on and community-based research skills; 2) attaining transferable skills they could carry with them in future positions; 3) acquiring CP-specific competencies; and 4) cultivating greater awareness and passion for social issues. Finally, the majority of respondents discussed how their involvement on CP research teams honed in their interest and passions and/or shaped their professional trajectory.  These findings provide preliminary evidence of the benefits of CP research involvement at an undergraduate level and has important implications for how CP as a field may choose to invest in undergraduate research opportunities.&nbsp