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There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype., Motor Neurone Disease Association (MNDA); Wellcome Trust; Medical Research Council; University of Manchester Centre for Integrated Genomic Medical Research (CIGMR); National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust; Dementia Biomedical Research Unit; Maudsley Biomedical Research Centre; King's Health Partners (Guy's and St Thomas' NHS Foundation Trust, King's College Hospital NHS Foundation Trust, King's College London and South London and Maudsley NHS Foundation Trust; Guy's and St Thomas' Charity; Health Data Research UK (HDR UK); ALS Association Milton Safenowitz Research Fellowship; European Research Council (ERC); EU Joint Programme-Neurodegenerative Disease Research (JPND); European Community's Health Seventh Framework Programme (FP7/2007-2013); European Union (EU); Horizon 2020; H2020-PHC-2014-two-stage; PPP Allowance; KU Leuven Opening the Future Fund; ALS Liga Belgie; Science Foundation Ireland; Project MinE; American ALS Association; National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke (NINDS)

This practical manual is designed to help medical officers in small hospitals provide safe and effective anesthesia for patients. Intended for doctors with at least one year of postgraduate clinical experience, it describes anesthetic techniques suitable for use in hospitals with limited resources. Chapter 2 describes fundamental principles and techniques underlying the practice of anesthesia and outlines immediate and continuing care of critically ill or unconscious patients. Chapter 3 focuses on continuing care of unconscious and anesthetized patients. The focus of Chapter 4 is on the principles of fluid and electrolyte therapy. Chapters 5 and 6 cover patient assessment before anesthesia and general anesthesia. Chapter 7 concerns safe clinical use of anesthetic equipment best-suited for and most likely found in district hospitals. Chapter 8 contains examples of general anesthetic techniques feasible in small or medium-sized hospitals. Chapter 9 provides information on drugs. Chapter 10 suggests techniques for conduction anesthesia. Chapters 11 and 12 discuss choosing and planning the anesthetic technique and postoperative care of the patient. Chapters 13 and 14 discuss special needs of pediatric and obstetric anaesthesia and important medical conditions. Chapter 15 covers oxygen, gas supplies, equipment, and maintenance. Numerous illustrations convey technical details; tables, charts, and checklists summarize lines of action and points to remember. Checklists and an index are appended. (YLB)

Development of a prototype data-driven modelling and visualisation tool to be tested with selected stakeholders. The prototype will be used to create a roadmap for visualising data leading to better coastal resilience decisions in the management of future sea level rise. The deliverable will include a brief report.

Der Aufsatz greift auf neue Forschungsimpulse zu einer ‚Epistemologie des Exemplarischen‘ zurück und bindet diese an Untersuchungsansätze zu exemplarischen Kurzerzählungen des Mittelalters. Er zeigt an drei beispielhaft ausgewählten Erzählungen (einer Fabel, einem historischen Exempel, einem Gleichnis), über welche Möglichkeiten die Kurzerzählungen verfügen, um die Relation zwischen Erzählung (narratio) und Epimythion (moralisatio) je neu zu entwerfen. Von jeder der drei Kurzerzählungen werden verschiedene Fassungen vorgestellt, die je kontextabhängig unterschiedliche narrative und argumentative Techniken nutzen, um aus einer Erzählung verschiedene Schlüsse zu ziehen und damit ihr rhetorisches Potential voll auszuschöpfen.

Family-level biotic metrics were originally designed to rapidly assess gross organic pollution effects, but came to be regarded as general measures of stream degradation. Improvements in water quality in developed countries have reignited debate about the limitations of family-level taxonomy to detect subtle change, and is resulting in a shift back towards generic and species-level analysis to assess smaller effects. Although the scale of pollution characterizing past condition of streams in developed countries persists in many developing regions, some areas are still considered to be only moderately disturbed. We sampled streams in Belize to investigate the ability of family-level macroinvertebrate metrics to detect change in stream catchments where less than 30% of forest had been cleared. Where disturbance did not co-vary with natural gradients of change, and in areas characterized by low intensity activities, none of the metrics tested detected significant change, despite evidence of environmental impacts. We highlight the need for further research to clarify the response of metrics to disturbance over a broader study area that allows replication for confounding sources of natural variation. We also recommend research to develop more detailed understanding of the taxonomy and ecology of Neotropical macroinvertebrates to improve the robustness of metric use.

Family-level biotic metrics were originally designed to rapidly assess gross organic pollution effects, but came to be regarded as general measures of stream degradation. Improvements in water quality in developed countries have reignited debate about the limitations of family-level taxonomy to detect subtle change, and is resulting in a shift back towards generic and species-level analysis to assess smaller effects. Although the scale of pollution characterizing past condition of streams in developed countries persists in many developing regions, some areas are still considered to be only moderately disturbed. We sampled streams in Belize to investigate the ability of family-level macroinvertebrate metrics to detect change in stream catchments where less than 30% of forest had been cleared. Where disturbance did not co-vary with natural gradients of change, and in areas characterized by low intensity activities, none of the metrics tested detected significant change, despite evidence of environmental impacts. We highlight the need for further research to clarify the response of metrics to disturbance over a broader study area that allows replication for confounding sources of natural variation. We also recommend research to develop more detailed understanding of the taxonomy and ecology of Neotropical macroinvertebrates to improve the robustness of metric use.

Project Risk and Cost Analysis focuses on risk in the context of project management, primarily in the area of risk’s effects on project costs, with emphasis on the many modern tools that help you and your organization quantify and manage project risk. You will learn how to perform a formal risk and cost analysis, apply the Earned Value Method to risk management, and adjust schedule and budget reserves appropriately for your project conditions. The book follows the basic project risk management approach as laid out in A Guide to the Project Management Body of Knowledge (PMBOK® Guide), 4th Edition, popularly known as the PMBOK® Guide, along with other sources listed in the bibliography and suggested reading. This is an ebook version of the AMA Self-Study course. If you want to take the course for credit you need to either purchase a hard copy of the course through amaselfstudy.org or purchase an online version of the course through www.flexstudy.com.