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"Morgan, Paul"
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Crime and justice since 1750
\"This book provides a comprehensive, introductory text for students taking courses in crime and criminal justice history. It covers all of the key historical topics central to an understanding of the current criminal justice system, including the development of the police, the courts and the mechanisms of punishment (from the gallows to the prison). The role of the victim in the criminal justice system, changing perceptions of criminals, long term trends in violent crime, and the rise of surveillance society also receive detailed analysis. In addressing each of these issues and developments, the authors draw on the latest research in this rapidly-expanding field to explore a range of historiographical and criminological debates. This new edition continues its exploration of criminal justice history right through to the present day and discusses recent events in the criminal justice world. Each chapter now ends with a 'Modern Parallels' section - a detailed case study providing historical analysis pertinent to a specific contemporary issue in the field of criminal justice and drawing parallels between historical context and modern phenomenon. Each chapter also includes a 'Key Questions' section, which guides the reader towards appropriate sources for further study. The authors draw on their in-depth knowledge and provide an accessible and lively guide for those approaching the subject for the first time, or those wishing to deepen their knowledge. This makes the book essential reading for those teaching or studying modules on criminal justice, policing and youth justice\"-- Provided by publisher.
Book
Complement in the pathogenesis of Alzheimer’s disease
The emergence of complement as an important player in normal brain development and pathological remodelling has come as a major surprise to most scientists working in neuroscience and almost all those working in complement. That a system, evolved to protect the host against infection, should have these unanticipated roles has forced a rethink about what complement might be doing in the brain in health and disease, where it is coming from, and whether we can, or indeed should, manipulate complement in the brain to improve function or restore homeostasis. Complement has been implicated in diverse neurological and neuropsychiatric diseases well reviewed elsewhere, from depression through epilepsy to demyelination and dementia, in most complement drives inflammation to exacerbate the disease. Here, I will focus on just one disease, the most common cause of dementia, Alzheimer’s disease. I will briefly review the current understanding of what complement does in the normal brain, noting, in particular, the many gaps in understanding, then describe how complement may influence the genesis and progression of pathology in Alzheimer’s disease. Finally, I will discuss the problems and pitfalls of therapeutic inhibition of complement in the Alzheimer brain.
Journal Article
Complement, a target for therapy in inflammatory and degenerative diseases
Key Points
Complement is a key component of immunity with crucial inflammatory and opsonic properties; inappropriate activation of complement triggers or exacerbates inflammatory disease.
Complement dysregulation is a core feature of some diseases and contributes to pathology in many others.
Approved agents have been developed for and are highly effective in some orphan applications, but their progress to use in more common diseases has been slow.
Numerous challenges, such as target concentration or high turnover, limit the efficacy of these agents in humans.
Numerous novel agents targeting different parts of the complement system in different ways are now emerging from pre-clinical studies and are entering Phase I/II trials; these agents bring the potential for more-effective and more-specific anti-complement therapies in disease.
Other agents, both biologic and small molecule, are in Phase II or III trials for both rare and common diseases — administration routes include localized (for example, intravitreal) and systemic routes.
There is an urgent need to develop biomarkers and imaging methods that enable monitoring of the effects and efficacy of anti-complement agents.
The complement cascade, a key regulator of innate immunity, is a rich source of potential therapeutic targets for diseases including autoimmune, inflammatory and degenerative disorders. Morgan and Harris discuss the progress made in modulating the complement system and the existing challenges, including dosing, localization of the drug to the target and how to interfere with protein–protein interactions.
The complement system is a key innate immune defence against infection and an important driver of inflammation; however, these very properties can also cause harm. Inappropriate or uncontrolled activation of complement can cause local and/or systemic inflammation, tissue damage and disease. Complement provides numerous options for drug development as it is a proteolytic cascade that involves nine specific proteases, unique multimolecular activation and lytic complexes, an arsenal of natural inhibitors, and numerous receptors that bind to activation fragments. Drug design is facilitated by the increasingly detailed structural understanding of the molecules involved in the complement system. Only two anti-complement drugs are currently on the market, but many more are being developed for diseases that include infectious, inflammatory, degenerative, traumatic and neoplastic disorders. In this Review, we describe the history, current landscape and future directions for anti-complement therapies.
Journal Article
The ‘Swallow Tail’ Appearance of the Healthy Nigrosome – A New Accurate Test of Parkinson's Disease: A Case-Control and Retrospective Cross-Sectional MRI Study at 3T
There is no well-established in vivo marker of nigral degeneration in Parkinson's disease (PD). An ideal imaging marker would directly mirror the loss of substantia nigra dopaminergic neurones, which is most prominent in sub-regions called nigrosomes. High-resolution, iron-sensitive, magnetic resonance imaging (MRI) at 7T allows direct nigrosome-1 visualisation in healthy people but not in PD. Here, we investigated the feasibility of nigrosome-1 detection using 3T - susceptibility-weighted (SWI) MRI and the diagnostic accuracy that can be achieved for diagnosing PD in a clinical population. 114 high-resolution 3T - SWI-scans were reviewed consisting of a prospective case-control study in 19 subjects (10 PD, 9 controls) and a retrospective cross-sectional study in 95 consecutive patients undergoing routine clinical SWI-scans (>50 years, 9 PD, 81 non-PD, 5 non-diagnostic studies excluded). Two raters independently classified subjects into PD and non-PD according to absence or presence of nigrosome-1, followed by consensus reading. Diagnostic accuracy was assessed against clinical diagnosis as gold standard. Absolute inter- and intra-rater agreement was ≥94% (kappa≥0.82, p<0.001). In the prospective study 8/9 control and 8/10 PD; and in the retrospective study 77/81 non-PD and all 9 PD subjects were correctly classified. Diagnostic accuracy of the retrospective cohort was: sensitivity 100%, specificity 95%, NPV 1, PPV 0.69 and accuracy 96% which dropped to 91% when including non-diagnostic scans ('intent to diagnose'). The healthy nigrosome-1 can be readily depicted on high-resolution 3T - SWI giving rise to a 'swallow tail' appearance of the dorsolateral substantia nigra, and this feature is lost in PD. Visual radiological assessment yielded a high diagnostic accuracy for PD vs. an unselected clinical control population. Assessing the substantia nigra on SWI for the typical 'swallow tail' appearance has potential to become a new and easy applicable 3T MRI diagnostic tool for nigral degeneration in PD.
Journal Article
Hassel Smith : paintings 1937-1997
\"This book on the Abstract Expressionist painter Hassel Smith illustrates all periods of the artist's many-faceted career. Considered by critics as a \"West Coast underground legend,\" Hassel Smith was an influential member of the experimental school of artists that emerged from post-World War II California. Together with Clyfford Still, Mark Rothko, and Richard Diebenkorn, Smith made his name at the California School of Fine Arts (now the San Francisco Art Institute) and from 1950 until the mid-1960s with successful exhibitions in Europe and on both coasts of the US. While his breakthrough paintings are characterized by their wildly vibrant brushstrokes and explosions of color, Smith was equally adept in a more restrained style, producing in later years the magisterial sequence of \"measured\" abstractions. As an initial burst of fame subsided, Smith continued to paint with unwavering energy. The result is a robust and dynamic body of work that reflects Smith's persistent curiosity and the breadth of his inquiry into the possibilities of painting. Long awaited by followers of the innovative art of the American Far West, this volume presents a full appreciation of Smith's achievement\"--Publisher's description.
Book
Science Achievement Gaps Begin Very Early, Persist, and Are Largely Explained by Modifiable Factors
We examined the age of onset, over-time dynamics, and mechanisms underlying science achievement gaps in U.S. elementary and middle schools. To do so, we estimated multilevel growth models that included as predictors children's own general knowledge, reading and mathematics achievement, behavioral self-regulation, sociodemographics, other child- and family-level characteristics (e.g., parenting quality), and school-level characteristics (e.g., racial, ethnic, and economic composition; school academic climate). Analyses of a longitudinal sample of 7,757 children indicated large gaps in general knowledge already evident at kindergarten entry. Kindergarten general knowledge was the strongest predictor of first-grade general knowledge, which in turn was the strongest predictor of children's science achievement from third to eighth grade. Large science achievement gaps were evident when science achievement measures first became available in third grade. These gaps persisted until at least the end of eighth grade. Most or all of the observed science achievement gaps were explained by the study's many predictors. Efforts to address science achievement gaps in the United States likely require intensified early intervention efforts, particularly those delivered before the primary grades. If unaddressed, science achievement gaps emerge by kindergarten and continue until at least the end of eighth grade.
Journal Article
Structural basis of complement membrane attack complex formation
In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.
The membrane attack complex (MAC) is an immune effector that kills pathogens by forming pores in their membrane. Here the authors use cryo-electron microscopy to reveal that the full MAC is an asymmetric pore with a split-washer configuration and identify a network of interactions that provide a basis for sequential assembly.
Journal Article