Just what is narrative urgency?

This article takes as its main point of departure a body of empirical research on reading and text processing, and makes particular reference to the type of experiments conducted in Egidi and Gerrig (2006) and Rapp and Gerrig (2006). Broadly put, these experiments (i) explore the psychology of readers’ preferences for narrative outcomes, (ii) examine the way readers react to characters’ goals and actions, and (iii) investigate how readers tend to identify with characters’ goals the more ‘urgently’ those goals are narrated. The present article signals how stylistics can productively enrich such experimental work. Stylistics, it is argued, is well equipped to deal with subtle and nuanced variations in textual patterns without losing sight of the broader cognitive and discoursal positioning of readers in relation to these patterns. Making particular reference to what might constitute narrative ‘urgency’, the article develops a model which amalgamates different strands of contemporary research in narrative stylistics. This model advances and elaborates three key components: a Stylistic Profile, a Burlesque Block and a Kuleshov Monitor. Developing analyses of, and informal informant tests on, examples of both fiction and film, the article calls for a more rounded and sophisticated understanding of style in empirical research on subjects’ responses to patterns in narrative.

Software Release Planning: An Evolutionary and Iterative Approach

Abstract To achieve higher flexibility and to better satisfy actual customer requirements, there is an increasing tendency to develop and deliver software in an incremental fashion. In adopting this process, requirements are delivered in releases and so a decision has to be made on which requirements should be delivered in which release. Three main considerations that need to be taken account of are the technical precedences inherent in the requirements, the typically conflicting priorities as determined by the representative stakeholders, as well as the balance between required and available effort. The technical precedence constraints relate to situations where one requirement cannot be implemented until another is completed or where one requirement is implemented in the same increment as another one. Stakeholder preferences may be based on the perceived value or urgency of delivered requirements to the different stakeholders involved. The technical priorities and individual stakeholder priorities may be in conflict and difficult to reconcile. This paper provides (i) a method for optimally allocating requirements to increments; (ii) a means of assessing and optimizing the degree to which the ordering conflicts with stakeholder priorities within technical precedence constraints; (iii) a means of balancing required and available resources for all increments; and (iv) an overall method called EVOLVE aimed at the continuous planning of incremental software development. The optimization method used is iterative and essentially based on a genetic algorithm. A set of the most promising candidate solutions is generated to support the final decision. The paper evaluates the proposed approach using a sample project.

Complexity and Conundrums in Pollution Control:Improving Effectiveness in Regulatory Compliance

The last century has witnessed a dramatic increase in the wealth of European nations and the well being of their inhabitants. The focus has, however, largely been upon economic growth to the detriment of people and the environment. It is only in recent years that governments have taken cognisance of the impacts of our actions and there is a growing realisation that the causal factors must be identified and addressed as a matter of urgency. One of the key problem areas is pollution and as such environmental protection has become increasingly important as a mechanism for safeguarding the quality of air, water and land. This involves a range of activities from setting standards to monitoring and reporting on discharges and emissions, through to the enforcement of legislation. In theory, this is a simple challenge, in practice, it has proven to be an extremely complex equation that might only begin to be addressed through research. In this context it is strange, and alarming, to find that while it is an axiom of good practice that policy is informed by research there has been a dearth of investigation in this field. The purpose of this paper is, therefore, to consider the issue of pollution, how it impacts on the environment, what measures have been established in pursuit of reducing the number of incidences and, most significantly, which strategies might be employed to avoid or ameliorate detrimental impacts.

The Evolution of European Identity: Using biographical methods to study the development of European identity

Based upon the original application to the European Commission, this article gives insights into the thinking of the Euroidentities team at the point that the project began. The question: “Is the European ‘identity project’ failing?” is posed in the sense that the political and economic attainments of the European Union have not been translated into a sense of identity with or commitment to Europe from the populaces that have benefited from them. The urgency of European ‘identity work’ is asserted with a number of levels for the construction of European identity being hypothesized. Euroidentities is intended to break conceptual ground by bringing together on an equal footing two apparently antagonistic views of identity -- the collective and institutional and the individual and biographical – to give a more anchored and nuanced view of identity formation and transformation than either can provide on its own. Rather than following the dominant approaches to research on European identity that have been macro-theoretical and ‘top-down’, retrospective in-depth qualitative biographical interviews are planned since they provide the ideal means of gaining insight into the formation of a European identity or multiple identities from the ‘bottom up’ perspective of non-elite groups. The reliability of analysis will be buttressed by the use of contrastive comparison between cases, culminating in contrastive comparison across the national project teams between cases drawn from different ‘sensitized groups’ that provide the fieldwork structure of the project. The paper concludes with a summary of some of the more significant findings.

Crowd Control? Depictions of the Many in Anglo-Saxon Literature, with Particular Reference to the Old English Legend of the Seven Sleepers

This article argues for the distinctiveness of the presentation of crowds in the Old English version of the Legend of the Seven Sleepers . In traditional Old English poetry, crowds are mostly conspicuous by their absence, since the social groupings portrayed are typically those ofthe lord's retinue and the fellowship of the hall. In writings deriving from Latin traditions (in Anglo-Latin, Old English prose and strands of Old English poetry) such as historiography andhagiography, crowds are presented in highly conventional terms based on literary models. The crowd scenes in the Legend of the Seven Sleepers , on the other hand, have an immediacy and urgency that seem based on real-life experience of Anglo-Saxon England rather than simply imitative of the work's Latin (ultimately Greek) source or of other literary models. Drawing upon crowd theory and historical studies, the article demonstrates that the crowds in this text are presented in “domesticated” Anglo-Saxon terms and may be seen as reflective of growing urbanization in late Anglo-Saxon England. “Real” crowds are glimpsed elsewhere in Anglo-Saxon literature but in the Legend of the Seven Sleepers they are particularly foregrounded; this text also presents the literature's liveliest picture of town life more generally.

The renin-angiotensin system and antihypertensive drugs in Alzheimer's disease:current standing of the angiotensin hypothesis?

There is an urgent need to improve upon Alzheimer's disease (AD) treatments. Limitations of existing drugs are that they target specific downstream neurochemical abnormalities while the upstream underlying pathology continues unchecked. Preferable treatments would be those that can target a number of the broad range of molecular and cellular abnormalities that occur in AD such as amyloid-ß (Aß) and hyperphosphorylated tau-mediated damage, inflammation, and mitochondrial dysfunction, as well more systemic abnormalities such as brain atrophy, impaired cerebral blood flow (CBF), and cerebrovascular disease. Recent pre-clinical, epidemiological, and a limited number of clinical investigations have shown that prevention of the signaling of the multifunctional and potent vasoconstrictor angiotensin II (Ang II) may offer broad benefits in AD. In addition to helping to ameliorate co-morbid hypertension, these drugs also likely improve diminished CBF which is common in AD and can contribute to focal Aß pathology. These drugs, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor antagonists (ARAs) may also help deteriorating cognitive function by preventing Ang II-mediated inhibition of acetylcholine release as well as interrupt the upregulation of deleterious inflammatory pathways that are widely recognized in AD. Given the current urgency to find better treatments for AD and the relatively immediate availability of drugs that are already widely prescribed for the treatment of hypertension, one of the largest modifiable risk factors for AD, this article reviews current knowledge as to the eligibility of ACE-inhibitors and ARAs for consideration in future clinical trials in AD.

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Abstract Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes.
It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage
and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major
track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body
of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the
strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in
the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract,
the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials
addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.

Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum

Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase-and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH 2-terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 a-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER. © 2012 Macmillan Publishers Limited All rights reserved.

Halophilic microorganisms as a source of novel antibiofilm compounds

Objectives: There is great urgency for alternate sources of antibiotics to be identified. One relatively untapped source of novel bioproducts, including antimicrobials, is organisms derived from extreme environments. Halophiles (which require high salt concentrations) are one such group which is being increasingly explored for their biotechnological potential. The aim of this study was to identify halophilic environmental isolates which possessed in vitro and in vivo antimicrobial and antibiofilm activities. Methods: 73 halophilic bacteria and archaea were isolated from Kilroot salt mine in Northern Ireland. Culture extracts of each isolate were screened for antimicrobial and antibiofilm activity against numerous pathogenic bacteria, including Staphylococcus species and Pseudomonas aeruginosa, both model strains and clinical isolates. The methods used included disc diffusion assays of crude extracts, MIC screening, the MBEC assay, and an in vivo model based on the Greater Wax Moth (Galleria mellonella). Results: The assays indicated >50% of extracts displayed antimicrobial and antibiofilm activity against at least one pathogen, the majority being Staphylococcus species, but also E. coli and P. aeruginosa. Biofilms were either reduced or eradicated by halophile extracts when tested with the MBEC device. Further experiments demonstrated that these effects could be replicated in vivo, with extracts reducing the severity of infections and enhancing the survival of infected G. mellonella. Conclusions: The importance of extremophiles to pharmaceutical research should not be underestimated. While not yet fully characterised, based on the data obtained, the halophiles isolated during this study may provide a promising reservoir of novel antimicrobial and antibiofilm compounds.

Non-invasive antidromic neurostimulation:A simple effective method for improving bladder storage

Patients with intractably diminished bladder storage function are encountered frequently by neurourologists, occasionally requiring reconstructive surgery for appropriate resolution. Although sacral neuromodulation is a recognized effective therapeutic modality, present techniques are technically demanding, invasive, and expensive. This study investigated the effect of non-invasive third sacral nerve (S3) stimulation on bladder activity during filling cystometry. One hundred forty-six patients underwent standard urodynamic filling cystometry that was then immediately repeated. Patients in the study group (n = 74) received antidromic transcutaneous sacral neurostimulation during the second fill and the control group (n = 72) underwent a second fill without neurostimulation. A statistically significant increase in bladder storage capacity without a corresponding rise in detrusor pressure was observed in the neurostimulated patients. This improvement in functional capacity is an encouraging finding that further supports the use of this non-invasive treatment modality in clinical practice. Neurourol. Urodynam. 20:73-84. 2001. (C) 2001 Wiley-Liss, Inc.

Transcutaneous sacral neurostimulation for irritative voiding dysfunction

with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief. Objective: Patients with irritative voiding dysfunction are often unresponsive to standard clinical treatment. We evaluated the response of such individuals to transcutaneous electrical stimulation of the third sacral nerve. Methods: 32 patients with refractory irritative voiding dysfunction (31 female and 1 male; mean age 47 years) were recruited to the study. Ambulatory transcutaneous electrical neurostimulation was applied bilaterally to the third sacral dermatomes for 1 week. Symptoms of frequency, nocturia, urgency, and bladder pain were scored by each patient throughout and up to 6 months following treatment. Results: The mean daytime frequency was reduced from 11.3 to 7.96 (p = 0.01). Nocturia episodes were reduced from a mean of 2.6 to 1.8 (p = 0.01). Urgency and bladder pain mean symptom scores were reduced from 5.97 to 4.89 and from 1.48 to 0.64, respectively. After stopping therapy, symptoms returned to pretreatment levels within 2 weeks in 40% of the patients and within 6 months in 100%, Three patients who continued with neurostimulation remained satisfied with this treatment modality at 6 months. Conclusions: Transcutaneous third sacral nerve stimulation may be an effective and noninvasive ambulatory technique for the treatment of patients with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief.

Enabling and constraining features of donor accountability and its relationship to beneficiary accountability

Purpose: The purpose of this paper is to theorise and empirically examine the views of various NGO stakeholders on the role of donors in facilitating beneficiary accountability.

Method: The paper adopts a case study design and draws primarily on semi-structured interviews with the officials of a large development NGO, donor representatives and regulators.

Findings: We find that donor accountability contains both enabling and constraining features in relation to beneficiary accountability. Our evidence shows that while legitimising their own actions, donors’ accountability requirements embed some enabling provisions of beneficiary accountability, such as participation, monitoring, evaluation and lessons learning, which facilitate beneficiary accountability (Ebrahim, 2003b). We argue that exerting the attributes of power, legitimacy and urgency donors are in a position to realise their accountability claims (Mitchell, Agle, & Wood, 1997) and can hold funded NGOs to account. In the absence of beneficiaries’ power and the unwillingness of regulators to hold NGOs to account, donors’ accountability can play a complementary role in making an NGO accountable to its beneficiaries. Finally, we capture and illustrate some constraining features of donor accountability which limits the promotion of beneficiary accountability.

Research limitations/implications: The findings have significant implications for the policy makers and donors in the context of the current phenomenon of NGOs drive for self-sustainability via commercial activities which are actively encouraged by the donors.

Originality: This paper provides an alternative theorisation of donor accountability in a development NGO context. It draws on rare qualitative empirical data which incorporate the views of multiple groups (including donors which is hitherto rare in the NGO accountability literature) who are directly and/or indirectly involved in setting and negotiating NGO-donors accountability relationship. It enhances our understanding in terms providing a more nuanced portrayal of donor accountability.

Using the hidden Markov model to capture quality of care in Lombardy geriatric wards

Quality of care is an important aspect of healthcare monitoring, which is used to ensure that the healthcare system is delivering care of the highest standard. With populations growing older there is an increased urgency in making sure that the healthcare delivered is of the highest standard. Healthcare providers are under increased pressure to ensure that this is the case with public and government demand expecting a healthcare system of the highest quality. Modelling quality of care is difficult to measure due to the many ways of defining it. This paper introduces a potential model which could be used to take quality of care into account when modelling length of stay. The Coxian phase-type distribution is used to model length of stay and the associated quality of care incorporated into the Coxian using a Hidden Markov model. Covariates are also introduced to determine their impact on the hidden level to find out what potentially can affect quality of care. This model is applied to geriatic patient data from the Lombardy region of Italy. The results obtained highlighted that bed numbers and the type of hospital (public or private) can have an effect on the quality of care delivered.

The value of tests in the diagnosis and management of glaucoma.

PURPOSE:

To assess the noneconomic value of tests used in the diagnosis and management of glaucoma, and explore the contexts and factors that determine such value.

DESIGN:

Perspective.

METHODS:

Selected articles from primary and secondary sources were reviewed and interpreted in the context of the authors' clinical and research experience, influenced by our perspectives on the tasks of reducing the global problem of irreversible blindness caused by glaucoma. The value of any test used in glaucoma is addressed by 3 questions regarding: its contexts, its kind of value, and its implicit or explicit benefits.

RESULTS:

Tonometry, slit-lamp gonioscopy, and optic disc evaluation remain the foundation of clinic-based case finding, whether in areas of more or less abundant resources. In resource-poor areas, there is urgency in identifying patients at risk for severe functional loss of vision; screening strategies have proven ineffective, and efforts are hindered by the inadequate allocation of support. In resource-abundant areas, the wider spectrum of glaucoma is addressed, with emphasis on early detection of structural changes of little functional consequence; these are increasingly the focus of new and expensive technologies whose clinical value has not been established in longitudinal and population-based studies. These contrasting realities in part reflect differences among the value ascribed, often implicitly, to the tests used in glaucoma.

CONCLUSIONS:

The value of any test is determined by 3 aspects: its context of usage; its comparative worth and to whom its benefit accrues; and how we define historically what we are testing. These multiple factors