Estimating the number of true null hypotheses and the false discovery rate from multiple discrete non-uniform permutation p-values

This dissertation addresses statistical issues that arise in a multiple testing framework when each of m hypotheses is tested via permutation methods. A standard error rate to control in multiple testing situations (especially when m ~ 104) is the false discovery rate which describes the expected ratio of type I errors to the total number of rejections. An adaptive approach to controlling the false discovery rate is to estimate the number of type I errors using a data-based estimate of m0, the number of true null hypotheses. Estimation of m0 has received much interest in recent years. Existing methods assume each of the m p-values has a continuous uniform (0,1) null distribution. This dissertation discusses numerous ways in which p-values may not have continuous uniform (0,1) null distributions and proposes how to estimate m0 and the false discovery rate in these scenarios. The first scenario involves a sequential permutation testing procedure that can substantially reduce computational expense when the test statistic is computationally intensive. The method is demonstrated via an application involving the genetic mapping of expression quantitative trait loci (eQTL). Other scenarios are motivated by problems that arise in genomics and proteomics

Remtech SSME nozzle design TPS

Thermal damage to the Space Shuttle Main Engine (SSME) aft manifold Thermal Protection System (TPS) has been observed for flights STS-8 through STS-13. This damaged area is located on the ME2 and ME3 and extends over a region of approximately one square foot. Total failure or burn-through of the TPS could lead to severe thermal damage of the SSME manifold and loss of an engine nozzle necessitating nozzle replacement causing significant schedule delays and cost increases. Thermal damage to the manifold can be defined as a situation where the manifold temperature becomes greater than 1300 F; thereby causing loss of heat treatment in the nozzle. Results of Orbiter/nozzle wind tunnel tests and Hot Gas Facility tests of the TPS are presented. Aerothermal and thermal analysis models for the SSME aft manifold are discussed along with the flight predictions, design trajectory and design environment. Finally, the TPS design concept and TPS thermal response are addressed

The impact of knowledge competences on business performance: Moderation effect of 3D printing implementation

3D Printing allows companies to have full-control over production processes, resulting in overall business performance improvements. However, this relationship closely correlated with knowledge management competences (KMCs), which are associated with project complexity. This research explores a three-way moderation effect among 3D printing implementation, KMCs, project complexity, and business performance

Christlich Demokratische Union Deutschlands e a identidade europeia da Alemanha

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Ciência Política e Relações Internacionais.A actual conjuntura política e económica europeia tem levantado questões de diversa ordem sobre o futuro do projecto de integração europeia, tanto a nível institucional como ideológico. O impacto destas sente-se de forma especial na Alemanha, situada no coração da Europa ao longo das últimas seis décadas, e contribuindo activamente para a sua arquitectura institucional. Com o abrandamento do motor de integração europeia e a difusão de uma incerteza funcional quanto à estrutura comunitária, aliada à crise do Euro, retoma-se o histórico debate da questão alemã, e sobre o papel a desempenhar pela Alemanha no seio de uma Europa democrática, mas cada vez mais paralisada do ponto de vista institucional. Numa perspectiva histórica, torna-se necessário perceber de que forma é que o contributo alemão para o projecto de construção europeia tem vindo a evoluir ao longo das décadas, e a pertinência deste na avaliação do compromisso alemão para com a Europa. O presente trabalho visa oferecer uma visão compreensiva do panorama político alemão entre o final da Segunda Guerra Mundial e a queda do muro de Berlim, como forma de estabelecer as bases históricas e ideológicas do pensamento europeísta alemão, fundamentalmente construído a partir do seu movimento democrata cristão. Para o efeito, isolam-se os momentos críticos na história da evolução ideológica e partidária da Christlich Demokratische Union Deutschlands (CDU), salientando os aspectos da sua doutrina que permitiram, ao longo da segunda metade do séc. XX, a convergência alemã com a Europa, paralela a um surpreendente processo de transição democrática

Scientific Visualization Using the Flow Analysis Software Toolkit (FAST)

Over the past few years the Flow Analysis Software Toolkit (FAST) has matured into a useful tool for visualizing and analyzing scientific data on high-performance graphics workstations. Originally designed for visualizing the results of fluid dynamics research, FAST has demonstrated its flexibility by being used in several other areas of scientific research. These research areas include earth and space sciences, acid rain and ozone modelling, and automotive design, just to name a few. This paper describes the current status of FAST, including the basic concepts, architecture, existing functionality and features, and some of the known applications for which FAST is being used. A few of the applications, by both NASA and non-NASA agencies, are outlined in more detail. Described in the Outlines are the goals of each visualization project, the techniques or 'tricks' used lo produce the desired results, and custom modifications to FAST, if any, done to further enhance the analysis. Some of the future directions for FAST are also described

Improved Management of Stillbirth using a Care Pathway.

PurposeEach year approximately 3,200 women have a stillbirth in the UK. Although national evidence-based guidance has existed since 2010, case reviews continue to identify suboptimal clinical care and communication with parents. Inconsistencies in management include induction and management of labour and the frequency of investigation after stillbirth. The paper aims to discuss these issues.Design/methodology/approachAn audit of stillbirths was performed in 2014 in 13 maternity units in the North West of England, this confirmed variation in practice described nationally. An integrated care pathway (ICP) was developed from national guidelines to enable optimal care for the management of stillbirth, reduce variation, standardise investigations and coordinate patient-focussed care. This was launched in 2015 and updated in 2016 to resolve the issues that were apparent after implementation.FindingsEach participating unit had commenced using the ICP by May 2015. Following implementation there were changes in care, most notably from diverse methods for the induction of labour to guideline-directed induction of labour. There were trends towards better care in terms of information given, choices offered, more appropriate analgesia in labour and improved post-delivery investigation for cause. Staff feedback about the ICP was positive.Practical implicationsThe use of this ICP improved care for women who had a stillbirth and their families. Issues with implementing a changed care pathway meant that further iterations were required, ongoing improvement is expected following the refinement of the ICP.Originality/valueICPs have been used for various clinical conditions. However, this is the first example of their use in women who had a stillbirth

Exploring the baseline knowledge and experience of healthcare professionals in the United Kingdom on Novel Psychoactive Substances

Submitted 28 january 2020. Reviwers' comments received 11 February 2020. Accepted 26 February 2020. Published 2 March 2020.Objective: This survey aimed to explore knowledge and experience on novel psychoactive substances (NPS) of healthcare professionals (HCPs). The study also aimed to assess how HCPs would like to improve their knowledge of NPS. Methods: Seventy paper questionnaires were disseminated in 2017 within continuing education events to pharmacists, nurses and general practitioners (GPs). Additionally, 127 online surveys were completed using the Qualtrics platform by other HCPs and mental health nurses in six United Kingdom (UK) independent mental health hospitals long-stay in-patient rehabilitation services. Two educational sessions involving pharmacists and GPs were also held in late 2017 and mid-2018. Knowledge of NPS by HCPs was evaluated prior to the start of the educational events. Evaluation forms were handed out post-sessions to garner feedback, especially on areas for improvement for future sessions. Statistical analysis of data was undertaken using SPSS (V.25). Results: Most HCPs reported only 'basic' to 'intermediate' NPS knowledge. Substance misuse service staff felt more informed, were more often consulted and had greater confidence regarding NPS compared to hospital and primary care professionals. A negative association was found between the age of the HCP and knowledge of NPS. Most participants expressed a need for regular training and updates as insufficient NPS-related information is currently received. Conclusions: An improvement within the self-reported knowledge of HCPs on NPS is evident in comparison to previous studies. Continued education of HCPs on NPS is fundamental for the provision of improved harm reduction services, which can enhance overall care for NPS service users.Peer reviewedFinal Published versio

Observing the NHS’s A&E performance objectives: is lean the cure?

Purpose The purpose of this paper is to investigate England’s Accident and Emergency (A&amp;E) portion of the National Health Service (NHS). This paper is based upon weekly published data from A&amp;E trusts across England, spanning from November 2010 to December 2014. Design/methodology/approach Emphasis is placed on a number of variables; month (time of year), performance (patients seen in less than four hours), patient volume and exploring the relationship between these variables. A deductive approach has been selected as the most appropriate for this paper and the format of a correlational study. Lean will be discussed as a philosophy throughout this paper, as a means to improve the NHS. Findings The NHS’s success in reaching its 95 per cent performance objective has in a gradual downwards trend since the data started being published and the volume of patients seen in A&amp;E is trending upwards. However, there is only a weak relationship between these variables, suggesting that peak in demand are effectively foretasted by the NHS and appropriate resources deployed to combat this. Additionally, there is a clear relationship between the time of year (month) and volume. Research limitations/implications The data used are not broken down and are aggregated from A&amp;E departments across the NHS in England. Therefore, outliers could be present that impact the data and results. Should outliers exist, these should be targeted for improvement or to be learnt from, depending on their ranking. Practical implications Should the NHS continue with their Lean transformation, it is believed that efficiency will improvement throughout the organisation. Social implications Through the identification of volume trends better care and efficiency can be provided to patients visiting the A&amp;E departments of the NHS. Originality/value This paper analyses data over the past four years which can be used to spot past trends and predict future trends, therefore smoothing the reliability and quality of the care offered to patients. This can be achieved through a Lean transformation and a flexible resourcing approach. </jats:sec

Chronic Trichuris muris infection in C57BL/6 mice causes significant changes in most microbiota and metabolome:effects reversed by pathogen clearance

Trichuris species are a globally important and prevalent group of intestinal helminth parasites, in which Trichuris muris (mouse whipworm) is an ideal model for this disease. This paper describes the first ever highly controlled and comprehensive investigation into the effects of T. muris infection on the faecal microbiota of mice and the effects on the microbiota following successful clearance of the infection. Communities were profiled using DGGE, 454 pyrosequencing, and metabolomics. Changes in microbial composition occurred between 14 and 28 days post infection, resulting in significant changes in α and β- diversity. This impact was dominated by a reduction in the diversity and abundance of Bacteroidetes, specifically Prevotella and Parabacteroides. Metabolomic analysis of stool samples of infected mice at day 41 showed significant differences to uninfected controls with a significant increase in the levels of a number of essential amino acids and a reduction in breakdown of dietary plant derived carbohydrates. The significant reduction in weight gain by infected mice probably reflects these metabolic changes and the incomplete digestion of dietary polysaccharides. Following clearance of infection the intestinal microbiota underwent additional changes gradually transitioning by day 91 towards a microbiota of an uninfected animal. These data indicate that the changes in microbiota as a consequence of infection were transitory requiring the presence of the pathogen for maintenance. Interestingly this was not observed for all of the key immune cell populations associated with chronic T. muris infection. This reflects the highly regulated chronic response and potential lasting immunological consequences of dysbiosis in the microbiota. Thus infection of T. muris causes a significant and substantial impact on intestinal microbiota and digestive function of mice with affects in long term immune regulation