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"Thompson, Louise"
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Making British law : committees in action
\"British Governments must pass laws if they are to survive, and Parliament is responsible for scrutinising these laws. We are used to seeing Members of Parliament in the House of Commons chamber, but we very rarely see them in committee, examining and debating the finer details of government bills. This book sheds light on the hidden world of House of Commons bill committees as they scrutinise legislation. Through a close analysis of government bills, it explores the inner workings of committees, revealing the widespread misconceptions of committee work. It also considers whether it is possible for backbenchers to change the law, examines the techniques and strategies they use to do this, and argues that committees are vital to the making of British law\"-- Provided by publisher.
Book
Empowering the Next Generation of Watershed Decision-Makers: A Pedagogical Design
Watershed management is the art and practice of understanding stakeholder values for ecosystem services within a watershed and instituting management practices that consider trade-offs to sustain these goods and services. Effective watershed management practices are hydrologically defined, ecosystem-based, inclusive, and integrate biophysical as well as socioeconomic decisions. The uncertainties and unpredictability of climate change create an ambiguous backdrop to the increasingly social problem of water resource management. Inequities in watershed decision-making processes often lead to the reinforcement of power and resource imbalances. Future watershed managers must be able to engage across socioeconomic and cultural boundaries to support decisions that advance water as a human right in an uncertain future. We offer a design for a graduate level, 15-week university course that uses publicly available resources to help emerging watershed leaders prepare for an uncertain future. The design is interactive and constructivist, engaging the refereed literature and leading to an increased understanding of ecosystem-based watershed management under climate scenarios, with special attention to vulnerable populations.
Journal Article
Microcephalic osteodysplastic primordial dwarfism type II is associated with global vascular disease
Background
Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is the most common form of primordial dwarfism, caused by bialleic mutations in the pericentrin gene (
PCNT
). Aside from its classic features, there are multiple associated medical complications, including a well-documented risk of neurovascular disease. Over the past several years, it has become apparent that additional vascular issues, as well as systemic hypertension and kidney disease may also be related to MOPDII. However, the frequency and extent of the vasculopathy was unclear. To help address this question, a vascular substudy was initiated within our Primordial Dwarfism Registry.
Results
Medical records from 47 individuals, living and deceased, ranging in age from 3 to 41 years of age were interrogated for this purpose. Of the total group, 64% were diagnosed with moyamoya, intracranial aneurysms, or both. In general, the age at diagnosis for moyamoya was younger than aneurysms, but the risk for neurovascular disease was throughout the shortened lifespan. In addition to neurovascular disease, renal, coronary and external carotid artery involvement are documented. 43% of the total group was diagnosed with hypertension, and 17% had myocardial infarctions. A total of 32% of the entire cohort had some form of chronic kidney disease, with 4% of the total group necessitating a kidney transplant. In addition, 38% had diabetes/insulin resistance. Ages of diagnoses, treatment modalities employed, and location of vasculopathies were notated as available and applicable, as well as frequencies of other comorbidities.
Conclusions
It is now clear that vascular disease in MOPDII is global and screening of the cardiac and renal vessels is warranted along with close monitoring of blood pressure. We recommend a blood pressure of 110/70 mmHg as a starting point for an upper limit, especially if the individual has a history of neurovascular disease, chronic kidney disease and/or diabetes. Additionally, providers need to be at high alert for the possibility of myocardial infarctions in young adults with MOPDII, so that appropriate treatment can be initiated promptly in an acute situation.
Journal Article
Curating genomic disease-gene relationships with Gene2Phenotype (G2P)
Genetically determined disorders are highly heterogenous in clinical presentation and underlying molecular mechanism. The evidence underpinning these conditions in the peer-reviewed literature requires robust critical evaluation for diagnostic use. Here, we present a structured curation process for Gene2Phenotype (G2P). This draws on multiple lines of clinical, bioinformatic and functional evidence. The process utilises and extends existing terminologies, allows for precise definition of the molecular basis of disease, and confidence levels to be attributed to a given gene-disease assertion. In-depth disease curation using this process will prove useful in applications including in diagnostics, research and development of targeted therapeutics. G2P:
www.ebi.ac.uk/gene2phenotype
.
Journal Article
NF-κB2 signalling in enteroids modulates enterocyte responses to secreted factors from bone marrow-derived dendritic cells
Alternative pathway NF-κB signalling regulates susceptibility towards developing inflammatory bowel disease (IBD), colitis-associated cancer and sepsis-associated intestinal epithelial cell apoptosis and shedding. However, the cell populations responsible for the perturbed alternative pathway NF-κB signalling in intestinal mucosal pathology remain unclear. In order to investigate the contribution of the epithelial compartment, we have tested whether NF-κB2 regulated transcription in intestinal epithelial cells controls the intestinal epithelial response to cytokines that are known to disrupt intestinal barrier permeability. Enteroids were generated from the proximal, middle and distal regions of small intestine (SI) from C57BL/6J wild-type mice and displayed region-specific morphology that was maintained during sub-culture. Enteroids treated with 100 ng/mL TNF were compared with corresponding regions of SI from C57BL/6J mice treated systemically with 0.33 mg/kg TNF for 1.5 h. TNF-induced apoptosis in all regions of the intestine in vitro and in vivo but resulted in Paneth cell degranulation only in proximal tissue-derived SI and enteroids. TNF also resulted in increased enteroid sphericity (quantified as circularity from two-dimensional bright field images). This response was dose and time-dependent and correlated with active caspase-3 immunopositivity. Proximal tissue-derived enteroids generated from
Nfκb2
−
/−
mice showed a significantly blunted circularity response following the addition of TNF, IFNγ, lipopolysaccharide (LPS) activated C57BL/6J-derived bone marrow-derived dendritic cells (BMDC) and secreted factors from LPS-activated BMDCs. However,
Nfκb1
−/−
mouse-derived enteroids showed no significant changes in response to these stimuli. In conclusion, the selection of SI region is important when designing enteroid studies as region-specific identity and response to stimuli such as TNF are maintained in culture. Intestinal epithelial cells are at least partially responsible for regulating their own fate by modulating NF-κB2 signalling in response to stimuli known to be involved in multiple intestinal and systemic diseases. Future studies are warranted to investigate the therapeutic potential of intestinal epithelial NF-κB2 inhibition.
Journal Article
Soluble Non-Starch Polysaccharides From Plantain (Musa x paradisiaca L.) Diminish Epithelial Impact of Clostridioides difficile
Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of C. difficile toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea. Interrupting these C. difficile -epithelium interactions could therefore represent a promising therapeutic strategy to prevent and treat CDI. Intake of dietary fibre is widely recognised as being beneficial for intestinal health, and we have previously shown that soluble non-starch polysaccharides (NSP) from plantain banana ( Musa spp.), can block epithelial adhesion and invasion of a number of gut pathogens, such as E. coli and Salmonellae. Here, we assessed the action of plantain NSP, and a range of alternative soluble plant fibres, for inhibitory action on epithelial interactions of C. difficile clinical isolates, purified endospore preparations and toxins. We found that plantain NSP possessed ability to disrupt epithelial adhesion of C. difficile vegetative cells and spores, with inhibitory activity against C. difficile found within the acidic (pectin-rich) polysaccharide component, through interaction with the intestinal epithelium. Similar activity was found with NSP purified from broccoli and leek, although seen to be less potent than NSP from plantain. Whilst plantain NSP could not block the interaction and intracellular action of purified C. difficile toxins, it significantly diminished the epithelial impact of C. difficile , reducing both bacteria and toxin induced inflammation, activation of caspase 3/7 and cytotoxicity in human intestinal cell-line and murine intestinal organoid cultures. Dietary supplementation with soluble NSP from plantain may therefore confer a protective effect in CDI patients by preventing adhesion of C. difficile to the mucosa, i.e. a “contrabiotic” effect, and diminishing its epithelial impact. This suggests that plantain soluble dietary fibre may be a therapeutically effective nutritional product for use in the prevention or treatment of CDI and antibiotic-associated diarrhoea.
Journal Article
Breastfeeding friendly pharmacies: a setting with potential
Pharmacists are often the most accessible medication expert for breastfeeding women, and need reliable resources to provide information about medications and safety with breastfeeding.1 It is known that they are often asked for breastfeeding related advice, and “with their highly visible roles in the community, frequent interactions with soon‐to‐be and new parents, and knowledge of medication safety, pharmacists can be a key component in breastfeeding promotion and support.”Many women cease breastfeeding unnecessarily due to fear of harm from drugs being excreted into breastmilk, and pharmacists may contribute to the misconception about this risk. Further, qualitative data from Australia suggests pharmacy staff most commonly respond to breastfeeding difficulties with advice about infant formula, rather than breastfeeding perseverance.5 Unnecessary cessation of breastfeeding is problematic: it not only deprives a child of the best conditions for health and nutrition, but may negatively affect the psychological wellbeing of the mother, due to lowered self‐esteem following discontinuation.
Journal Article
Using audience response systems to amplify student learning in political science: a case study of electoral systems teaching
Audience response systems (ARS) are now a very widespread technological teaching tool within political science, being used as either an opinion polling or an assessment tool in the classroom. This article presents a case study of an in-class demonstration using an ARS within an electoral systems and voting behaviour module to illustrate how these systems can be used in more innovative pedagogical ways to produce ‘teachable moments’ which facilitate high-level learning outcomes. It argues that political scientists should further emphasise the integration of pedagogical knowledge with technology and content knowledge to embed ARS technology within a more transformative learning process in order to amplify students’ understanding of political science concepts and aid the progression of learning.
Journal Article