Shock-excited molecular hydrogen in the outflows of post-asymptotic giant branch stars

Since the identi cation of proto-planetary nebulae (PPNe) as transition objects between the asymptotic giant branch stars and planetary nebulae more than two decades ago, astronomers have attempted to characterise these exciting objects. Today many questions still elude a conclusive answer, partly due to the sheer diversity observed within this small subset of stellar objects, and partly due to the low numbers detected. Fortunately, many of these objects display a rich spectrum of emission/absorption lines that can be used as diagnostics for these nebulae. This dissertation presents a study of six PPNe using the relatively new (at NIR wavelengths) integral eld spectroscopy technique. This method has allowed the investigation of distinct regions of these nebulae, and in certain cases the application of magneto-hydrodynamic shock models to the data. The goal of this research has been to investigate the evolution of PPNe by detailed examination of a small sample of objects consisting of a full range of evolutionary types. Near-IR ro-vibrational lines were employed as the primary tool to tackle this problem. In all six sources the 1!0S(1) line is used to map the spatial extent of the H2. In three of these objects the maps represent the rst images of their H2 emission nebulae. In the case of the earliest-type object (IRAS 14331-6435) in this sample, the line map gives the rst image of its nebula at any wavelength. In the only M-type object (OH 231.8+4.2) in the sample, high-velocity H2 is detected in discrete clumps along the edges of the bipolar out ow, while a possible ring of slower moving H2 is found around the equatorial region. This is the rst detection of H2 in such a late-type object but due its peculiarities, it is possibly not representative of what is expected of M-type objects. In IRAS 19500-1709, an intermediate-type object, the line map shows the H2 emission to originate in clumpy structures along the edges of a bipolar shell/out ow. The remaining three objects have all been the subject of previous studies but in each case new H2 lines are detected in this work along with other emission lines (Mg ii, Na i & CO). In the case of IRAS 16594-4656, MHD shock models have been used to determine the gas density and shock velocity. Two new python modules/classes have been written. The rst one to deal with the data cubes, extract ux measurements, rebin regions of interest, and produce line maps. The second class allows the easy calculation of many important parameters, for example, excitation temperatures, column density ratio values, extinction estimates from several line-pairs, column density values, and total mass of the H2. The class also allows the production of input les for the shock tting procedure, and simulated shocks for testing this tting process. A new framework to t NIR shock models to data has been developed, employing Monte Carlo techniques and the extensive computing cluster at the University of Hertfordshire (UH). This method builds on the approach used by many other authors, with the added advantages that this framework provides a method of correctly sampling the shock model parameter space, and providing error estimates on the model t. Using this approach, data from IRAS 16594-4656 have been successfully modelled using the shock models. A full description of this class of stellar objects from such a small sample is not possible due to their diverse nature. Although H2 was detected across the full spectral vi range of post-AGB objects, the phase at which H2 emission begins is still not clear. The only M-type object in this work is a peculiar object and may not be representative of a typical post-AGB star. The H2 PPNe appear to be located at lower Galactic latitudes (b 20 ) than the total PPNe population, possibly pointing to an above average mass and hence younger age of these objects

The hidden potential of organisational planning: matching Alexander's theory of patterns to practice

Generally, it is true of people that they will look for patterns and attach meaning to the patterns they find. Alexander et al. (1977) originally conceived the concept of pattern languages within the architecture community and since the early 1990s patterning has been used widely to document software development practices. Most uses of these patterning efforts have focussed on software from a technical aspect; however, authors such as Coplien & Harrison (2004) have moved beyond purely technical aspects and have used the concept of patterns to discuss issues of organization structure. As demand on managers and their time has increased substantially in recent times, streamlining and making traditional management processes more efficient and time effective has become an area of increasing concern. Management has become a hugely complex and demanding task on people. Further, there is a significant cost to the organization to ensure management staff are trained and capable in their role.The ability of managers to make good decisions in all aspects of management clearly affects the success of the organization as a whole. The volume of processes managers are expected to understand and involve themselves in, and the rate at which the environment and processes change, has led to the development of a variety of business process management tools. Most business process management tools are used to manage, track or simplify core processes by recognising patterns that can be replicated easily to produce more efficient management and more effective outcomes. However, there is limited research and development of process management tools for the traditional management processes of planning, leading, organizing and controlling.Despite the potential for improved understanding, training and practice of planning, there is a dearth of literature or practical resources developed on the concept of management patterns. Flexible patterns would allow simple comparison between the model and the actual situation, thus providing a direct link between theory and practice and facilitating easy change to the conceptual model or adjustment to the practice or both. The challenge for researchers in this relatively new area of study is to map and codify existing management processes, fill in the gaps in knowledge and bring the work to the attention of the business community, writers in the business community and business academics.The current study linked the management process of planning with Alexander et al.?s (1977) concept of patterns developed within architecture and later expanded to the information systems arena. The major focus of the study was to propose a model for identifying patterns in the management process of planning. The model was developed from responses received from managers as to the management planning process in ten organisational workplaces from a range of industries.Whether practitioners seek continuous improvement through controlling business inputs or processes, planning of outcomes is critical. Practical implementation difficulties continue despite a plethora of independent planning tools/applications. Using Alexander?s concept of ?patterning?, an underlying pattern that faithfully represents actual planning practices has been identified. Despite idiosyncracies in organisations, there are common themes that fit planning in public/private sectors alike; they can be used to improve dramatically the success of professional planning practices

Antitumour responses induced by a cell-based Reovirus vaccine in murine lung and melanoma models

Background: The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials. It has been shown to induce immune responses to tumours with very low toxicities. Methods: In this study, Reovirus was examined in two main approaches in vivo, in mice, using the melanoma B16F10 and Lewis Lung Carcinoma (LLC) models. Initially, mice were treated intratumourally (IT) with Reovirus and the immune responses determined by cytokine analysis. Mice were also vaccinated using a cell-based Reovirus vaccine and subsequently exposed to a tumourigenic dose of cells (B16F10 or LLC). Using the same cell-based Reovirus vaccine, established tumours were treated and subsequent immune responses and virus retrieval investigated. Results: Upregulation of several cytokines was observed following treatment and replication-competent virus was also retrieved from treated tumours. Varying levels of cytokine upregulation were observed and no replication-competent virus was retrieved in vaccine-treated mice. Prolongation of survival and delayed tumour growth were observed in all models and an immune response to Reovirus, either using Reovirus alone or a cell-based vaccine was also observed in all mice. Conclusion: This study provides evidence of immune response to tumours using a cell-based Reovirus vaccine in both tumour models investigated, B16F10 and LLC, cytokine induction was observed with prolongation of survival in almost all cases which may suggest a new method for using Reovirus in the clinic

Combination of electroporation delivered metabolic modulators with low-dose chemotherapy in osteosarcoma

Background: Osteosarcoma accounts for roughly 60% of all malignant bone tumors in children and young adults. The five-year survival rate for localized tumors after surgery and chemotherapy is approximately 70% whilst it drastically reduces to 15–30% in metastatic cases. Metabolic modulation is known to increase sensitivity of cancers to chemotherapy. A novel treatment strategy in Osteosarcoma is needed to battle this devastating malady. Results: Electroporation-delivered metabolic modulators were more effective in halting the cell cycle of Osteosarcoma cells and this negatively affects their ability to recover and proliferate, as shown in colony formation assays. Electroporation-delivered metabolic modulators increase the sensitivity of Osteosarcoma cells to chemotherapy and this combination reduces their survivability. Conclusion: This novel treatment approach highlights the efficacy of electroporation in the delivery of metabolic modulators in Osteosarcoma cells, and increased sensitivity to chemotherapy allowing for a lower dose to be therapeutic. Methods: Metabolic modulations of two Osteosarcoma cell lines were performed with clinically available modulators delivered using electroporation, and its combination with low-dose Cisplatin. The effects of Dicholoroacetic acid, 2-Deoxy-D-glucose and Metformin on cell cycle and recovery of Osteosarcoma cells were assessed. Their sensitivity to chemotherapy was also assessed when treated in combination with electroporation-delivered metabolic modulators

Plain language summary of the CheckMate 816 study results: nivolumab plus chemotherapy given before surgery for non–small-cell lung cancer

Immunotherapy; Neoadjuvant treatment; Presurgery treatmentImmunoteràpia; Tractament neoadjuvant; Tractament preoperatoriInmunoterapia; Tratamiento neoadyuvante; Tratamiento preoperatorioWhat is this summary about?: In this article, we summarize results from the ongoing phase 3 CheckMate 816 clinical study that were published in The New England Journal of Medicine in 2022. The goal of CheckMate 816 was to find out if nivolumab, an immunotherapy that activates a person's immune system (the body's natural defense system) to fight cancer, plus chemotherapy works better than chemotherapy alone when given before surgery in people with non-small-cell lung cancer (NSCLC) that can be removed surgically (resectable NSCLC). What happened in the study?: Adults who had not previously taken medications to treat NSCLC and whose cancer could be removed with surgery were included in CheckMate 816. During this study, a computer randomly assigned the treatment each person would receive before surgery for NSCLC. In total, 179 people were randomly assigned to receive nivolumab plus chemotherapy, and 179 people were randomly assigned to receive chemotherapy alone. The researchers assessed whether people who received nivolumab plus chemotherapy lived longer without the cancer geting worse or coming back and whether there were any cancer cells left in the tumor and lymph nodes removed by surgery. The researchers also assessed how adding nivolumab to chemotherapy affected the timing and outcomes of surgery and whether the combination of these drugs was safe. What were the results?: Researchers found that people who took nivolumab plus chemotherapy lived longer without the cancer getting worse or coming back compared with those who took chemotherapy alone. More people in the nivolumab plus chemotherapy group had no cancer cells left in the tumor and lymph nodes removed by surgery. Most people went on to have surgery in both treatment groups; the people who took nivolumab plus chemotherapy instead of chemotherapy alone had less extensive surgeries and were more likely to have good outcomes after less extensive surgeries. Adding nivolumab to chemotherapy did not lead to an increase in the rate of side effects compared with chemotherapy alone, and side effects were generally mild and manageable. What do the results of the study mean?: Results from CheckMate 816 support the benefit of using nivolumab plus chemotherapy before surgery for people with resectable NSCLC.The CheckMate 816 study was sponsored by Bristol Myers Squibb

Expressional changes in stemness markers post electrochemotherapy in pancreatic cancer cells

Pancreatic cancer is one of the most lethal cancers with high metastatic potential and strong chemoresistance. The capability of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor recurrence. The aim of our study was to illustrate electrochemotherapy as an effective treatment for pancreatic cancer along with the expression change in stemness genes (Nanog, Sox2 and Oct3/4) in pancreatic cancer cells post electrochemotherapy with bleomycin, cisplatin and oxaliplatin. Our results showed the enhanced expression of Nanog and decreased expression level of Oct3/4 after electrochemotherpy. We thus propose that these stemness markerS may have important roles in the initiation and/or recurrence of pancreatic cancer, and consequently may serve as important molecular diagnostics and/or therapeutic targets for the development of novel treatment strategies in pancreatic cancer patients. In conclusion, targeting these stemness factors could potentially improve electrochemotherapy as a treatment and preventing recurrence

Sexually dimorphic gene expression in bovine conceptuses at the initiation of implantation

In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of interferon tau (IFNT) by the conceptus. The endometrium can distinguish between embryos with different developmental competencies. In eutherian mammals, X-chromosome inactivation (XCI) is required to ensure an equal transcriptional level of most X-linked genes for both male and female embryos in adult tissues, but this process is markedly different in cattle than mice. We examined how sexual dimorphism affected conceptus transcript abundance and amino acid composition as well as the endometrial transcriptome during the peri-implantation period of pregnancy. Of the 5132 genes that were differentially expressed on Day 19 in male compared to female conceptuses, 2.7% were located on the X-chromosome. Concentrations of specific amino acids were higher in the uterine luminal fluid of male compared to female conceptuses, while female conceptuses had higher transcript abundance of specific amino acid transporters (SLC6A19 and SLC1A35). Of note, the endometrial transcriptome was not different in cattle gestating a male or a female conceptus. These data support the hypothesis that, far from being a blastocyst specific phenomenon, XCI is incomplete before and during implantation in cattle. Despite differences in transcript abundance and amino acid utilization in male versus female conceptuses, the sex of the conceptus itself does not elicit a different transcriptomic response in the endometrium

The effect of adult Early Warning Systems education on nurses' knowledge, confidence and clinical performance: A systematic review

Aims: This review aims to determine the effect of adult Early Warning Systems education on nurses’ knowledge, confidence and clinical performance. Background: Early Warning Systems support timely identification of clinical deterioration and prevention of avoidable deaths. Several educational programmes have been designed to help nurses recognize and manage deteriorating patients. Little is known as to the effectiveness of these programmes. Design: Systematic review. Data sources: Academic Search Complete, CINAHL, MEDLINE, PsycINFO, PsycARTICLES, Psychology and Behavioral Science Collection, SocINDEX and the UK & Ireland Reference Centre, EMBASE, the Turning Research Into Practice database, the Cochrane Central Register of Controlled Trials (CENTRAL) and Grey Literature sources were searched between October and November 2015. Review methods: This is a quantitative systematic review using Cochrane methods. Studies published between January 2011 - November 2015 in English were sought. The risk of bias, level of evidence and the quality of evidence per outcome were assessed. Results: Eleven articles with 10 studies were included. Nine studies addressed clinical performance, four addressed knowledge and two addressed confidence. Knowledge, vital signs recording and Early Warning Score calculation were improved in the short term. Two interventions had no effect on nurses’ response to clinical deterioration and use of communication tools. Conclusion: This review highlights the importance of measuring outcomes using standardized tools and valid and reliable instruments. Using longitudinal designs, researchers are encouraged to investigate the effect of Early Warning Systems educational programmes. These can include interactive e-learning, on-site interdisciplinary Early Warning Scoring systems training sessions and simulated scenarios

Challenging the 'New Professionalism': from managerialism to pedagogy?

In recent years there have been changes made to the conceptualisation of continuing professional development for teachers in both the Scottish and English systems of education. These changes have been instigated by successive UK governments (and more recently, by the Scottish Executive), together with the General teaching Council for Scotland (GTCS) and the General Teaching Council for England (GTCE). This paper argues that these changes have not provided a clear rationale for CPD, but instead have introduced tensions between the concept of teacher education and that of training. The need for a less confused understanding of CPD and its purposes is underlined, as is the need for school based approaches to continuing teacher education. Arguably, teacher education must move from technicist emphases to a model which integrates the social processes of change within society and schools with the individual development and empowerment of teachers