Homebound: STS-M1301 A Study on Television Writing in the Science Fiction Genre

This project is a scene-by-scene outline of an original television pilot script in the science fiction genre. The outline is based on research conducted in both the television and science fiction fields, providing the project with a firm foundation in television screenwriting structure as well as insights into the characteristics of the science fiction genre. Additional research was carried out on the topic of developing realistic, engaging characters for the screen. This project serves to broaden the writer’s portfolio upon graduation while giving him a chance to study the world of television, which contains numerous differences from the field of cinematic arts

Evidence-Based Genetics and Identification of Key Human Alzheimer’s Disease Alleles with Co-morbidities

Advancements in biomedical research have contributed to increasing the life expectancy of humans, but we now observe an increase in age-related diseases such as Alzheimer’s disease. Genome-Wide Association Studies (GWAS) and linkage studies have identified human genes associated with Alzheimer’s disease (referred to as AD genes). A previous study by Vahdati in 2017 has revealed the human AD genes and counterparts in model species [1]. Thus, we further investigate the co-morbidity genes and alleles. Using ontology analysis combined with cluster analysis, the study identified functional pathways enriched among the human AD genes, including 179 genes out of 695 human AD genes (26%) that were associated with one or more of the four neurological diseases including Amyotrophic lateral sclerosis, Multiple sclerosis, Parkinson’s disease, and Schizophrenia [1]. More importantly, the results indicate co-morbidities with Late-Onset Alzheimer’s Disease (LOAD) and other neurological conditions, implying the complexity of the phenotypes in the human AD. The co-morbidity genes may account for mixed symptoms for human AD as well as age-related risks of infections. Of them, the three genes are well conserved (Angiotensin I Converting Enzyme gene, ACE; Methylenetetrahydrofolate Reductase gene, MTHFR; and tumor necrosis factor gene, TNF). In this study, we confirmed the comorbidity of the three genes associated with AD. We further identified the comorbidity of two alleles in the MTHFR gene, C677T and A222V, significantly associated with Alzheimer’s disease. This study provides an example of evidencebased analysis that is cost-effective and may be an effective approach to develop cure-alls for multiple diseases

Stress and burnout in Improving Access to Psychological Therapies (IAPT) trainees: a Systematic Review

For more than a decade, Improving Access to Psychological Therapies (IAPT) has been training a new workforce of psychological therapists. Despite evidence of stress and burnout both in trainee mental health professionals, and qualified IAPT clinicians, little is known about these topics in IAPT trainees. Consequently, this systematic review sought to establish the current state of the literature regarding stress and burnout in IAPT trainees. Electronic databases were searched to identify all published and available unpublished work relating to the topic. On the basis of pre-established eligibility criteria, 8 studies (including 6 unpublished doctoral theses) were identified and assessed for quality. This review identifies that research into the experience of IAPT trainees is under-developed. Existing evidence tentatively suggests that IAPT trainees may experience levels of stress and burnout that are higher than their qualified peers and among the higher end of healthcare professionals more generally. The experience of fulfilling dual roles as mental health professionals and university students concurrently appears to be a significant source of stress for IAPT trainees. More research regarding the levels and sources of stress and burnout in IAPT trainees is urgently needed to confirm and extend these findings. Recommendations for future research in the area are given

The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis

The diagnosis of chronic myelomonocytic leukaemia (CMML) remains centred on morphology, meaning the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis however have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel to current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (n=283). Results were correlated with the morphological diagnosis and objective outcome measures including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) though also in 57% of patients with non-diagnostic BM features. The OS in non-diagnostic mutated patients was indistinguishable from those with CMML (p=0.118) and significantly worse than unmutated patients (p=0.0002). On multivariate analysis age, ASXL1, CBL, DNMT3A, NRAS & RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive fall in haemoglobin/platelet levels and increasing monocyte counts compared with mutation negative patients. Of note, the immunophenotypic features of non-diagnostic mutated patients were comparable to CMML patients and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis irrespective of diagnosis. In those without a WHO defined diagnosis, the mutation spectrum, immunophenotypic features and OS are indistinguishable from CMML patients and these patients should be managed as such

In Vivo Optical Metabolic Imaging of Long-Chain Fatty Acid Uptake in Orthotopic Models of Triple-Negative Breast Cancer

Targeting a tumor’s metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, we developed a quantitative optical approach to spatially and longitudinally map the kinetics of long-chain fatty acid uptake in in vivo murine models of breast cancer using a fluorescently labeled palmitate molecule, Bodipy FL c16. We chose intra-vital microscopy of mammary tumor windows to validate our approach in two orthotopic breast cancer models: a MYC-overexpressing, transgenic, triple-negative breast cancer (TNBC) model and a murine model of the 4T1 family. Following injection, Bodipy FL c16 fluorescence increased and reached its maximum after approximately 30 min, with the signal remaining stable during the 30–80 min post-injection period. We used the fluorescence at 60 min (Bodipy60), the mid-point in the plateau region, as a summary parameter to quantify Bodipy FL c16 fluorescence in subsequent experiments. Using our imaging platform, we observed a two- to four-fold decrease in fatty acid uptake in response to the downregulation of the MYC oncogene, consistent with findings from in vitro metabolic assays. In contrast, our imaging studies report an increase in fatty acid uptake with tumor aggressiveness (6NR, 4T07, and 4T1), and uptake was significantly decreased after treatment with a fatty acid transport inhibitor, perphenazine, in both normal mammary pads and in the most aggressive 4T1 tumor model. Our approach fills an important gap between in vitro assays providing rich metabolic information at static time points and imaging approaches visualizing metabolism in whole organs at a reduced resolution

Powering West Midlands Growth: A Regional Approach to Clean Energy Innovation

The West Midlands is uniquely positioned to lead the UK in taking advantage of the economic opportunities arising from the global transition to a clean energy system. The region’s strengths include: strong and coherent political leadership committed to sustainability; the diversity of economic needs and scale of demand required to build competitive markets to support radical innovation; a world-class concentration of both academic and commercial expertise in the low-carbon energy sector; a massive programme of public and private investment in infrastructure planned for the next decade, and above all, the determination to secure long-term economic benefit from clean energy innovation. This report makes the case for the creation of a small number of Energy Innovation Zones (EIZs) across the region, acting as pathfinders for an approach that might subsequently be adopted across the country as a whole. EIZs enable barriers – such as powerful institutional silos separating transport, digital, planning and energy – to be overcome within designated geographies. They create a risk-managed and commercial-scale context for the development of new local clean energy markets. They also provide a practical mechanism to help attract investment and muster local political support. At a national level, they can help ensure innovation is built into the government’s strategic sector deals and other large scale public investment projects

Interpreting the mammal deposits of Cloggs Cave (SE Australia), GunaiKurnai Aboriginal Country, through community-led partnership research

Palaeontological animal bone deposits are rarely investigated through research partnerships where the local First Nations communities have a defining hand in both the research questions asked and the research processes. Here we report research undertaken through such a partnership approach at the iconic archaeological site of Cloggs Cave (GunaiKurnai Country, East Gippsland), in the southern foothills of SE Australia's Great Dividing Range. A new excavation was combined with detailed chronometric dating, high-resolution 3D mapping and geomorphological studies. This allowed interpretation of a sequence of stratigraphic layers spanning from a lowermost excavated mixed layer dated to between 25,640 and 48,470 cal BP, to a dense set of uppermost, ash layers dated to between 1460 and 3360 cal BP. This long and well-dated chronostratigraphic sequence enabled temporal trends in the abundant small mammal remains to be examined. The fossil assemblage consists of at least 31 taxa of mammals which change in proportions through time. Despite clear evidence that the Old Ancestors repeatedly carried vegetation into the cave to fuel cool fires (no visible vegetation grows in Cloggs Cave), we observed little to no evidence of cooking fires or calcined bone, suggesting that people had little involvement with the accumulation of the faunal remains. Small mammal bones were most likely deposited in the cave by large disc-faced owls, Tyto novaehollandae (Masked Owl) or Tyto tenebricosa (Sooty Owl). Despite being well dated and largely undisturbed, the Cloggs Cave assemblage does not appear to track known Late Quaternary environmental change. Instead, the complex geomorphology of the area fostered a vegetation mosaic that supported mammals with divergent habitat preferences. The faunal deposit suggests a local ancestral landscape characterised by a resilient mosaic of habitats that persisted over thousands of years, signalling that the Old Ancestors burned landscape fires to encourage and manage patches of different vegetation types and ages within and through periods of climate change

Ki67 Proliferation Index as a Tool for Chemotherapy Decisions During and After Neoadjuvant Aromatase Inhibitor Treatment of Breast Cancer: Results From the American College of Surgeons Oncology Group Z1031 Trial (Alliance)

To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI)