OAK (Online Access to Knowledge) Commons (Young Harris College)
Not a member yet
33676 research outputs found
Sort by
Regenerative Potential of Hydrogels for Intracerebral Hemorrhage: Lessons from Ischemic Stroke and Traumatic Brain Injury Research
No full textIntracerebral hemorrhage (ICH) is a deadly and debilitating type of stroke, caused by the rupture of cerebral blood vessels. To date, there are no restorative interventions approved for use in ICH patients, highlighting a critical unmet need. ICH shares some pathological features with other acute brain injuries such as ischemic stroke (IS) and traumatic brain injury (TBI), including the loss of brain tissue, disruption of the blood-brain barrier, and activation of a potent inflammatory response. New biomaterials such as hydrogels have been recently investigated for their therapeutic benefit in both experimental IS and TBI, owing to their provision of architectural support for damaged brain tissue and ability to deliver cellular and molecular therapies. Conversely, research on the use of hydrogels for ICH therapy is still in its infancy, with very few published reports investigating their therapeutic potential. In this review, we comment on the published use of hydrogels in experimental ICH and describe how approaches reported in the IS and TBI fields may be applied to ICH research to inform the design of future therapies. We also highlight unique aspects of ICH that are distinct from IS and TBI that should be considered when translating biomaterial-based therapies between disease models
Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) mimicking idiopathic inflammatory myopathy: key points to prevent misdiagnosis
No full textObjectives: Diagnosing the idiopathic inflammatory myopathies (IIMs) can be challenging as several conditions, including genetic myopathies such as limb girdle muscular dystrophy type R12 (LGMD 2L, anoctaminopathy), mimic the presentation. Here we describe learning points identified from review of four patients with LGMD 2L who were initially incorrectly diagnosed with IIM. Our aim is to provide clinicians working in adult rheumatology services with a toolkit to help identify non-inflammatory presentations of myopathy. Methods: We performed retrospective review of medical notes, laboratory results, muscle imaging and histological findings of four patients with LGMD 2L who were previously misdiagnosed with IIM. We focused on clinical presentation and progression, therapeutic agents used, and events leading to revision of the diagnosis. Results: Three males and one female patients with a mean age of 51 years at presentation were reviewed. In each case treatment with immunosuppressants, in one case for >15 years, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and available myositis-associated/specific autoantibodies and associated connective tissue disease features were absent. Prominent fatty infiltration and selective muscle involvement on thigh muscle magnetic resonance imaging was a common. Conclusions: Adult-onset genetic myopathies, particularly LGMD R12, can mimic IIM. Accurate diagnosis is crucial to avoid use of potentially harmful immunosuppressive therapies, allow appropriate genetic counselling, and facilitate involvement in research studies
Understanding the sources of medication safety incidents in mental health hospitals: A mixed methods analysis of incidents reported to the National Reporting and Learning System
No full textBackground Medication safety incidents commonly occur in mental health hospitals. There is a need to improve understanding of the circumstances, actions or influences which are thought to have played a part in the origin of these medication incidents in order to design safer systems to improve patient safety. Aim To undertake a mixed-methods analysis of medication safety incidents reported to the National Reporting and Learning System (NRLS) in England and Wales during 2010-2017. Method Descriptive analyses were undertaken of all anonymised medication safety incidents reported to the NRLS over an eight-year period to characterise their type, severity, and the medication(s) involved. Secondly, a thematic analysis of the free-text reports for incidents reported with moderate or more serious outcomes was undertaken to identify the underlying contributory factors. ResultIn total, 93,727 medication incident reports were identified and 10.4% (n=9,755) described harmful outcomes. Administration errors accounted for the majority of medication incidents reported (50,314; 53.6%), followed by prescribing (15,480; 16.5%) and dispensing errors (10,871; 11.6%). Omission of medication (17,210; 18.3%), wrong frequency (11,860; 12.6%) and wrong/unclear dose of medication (10,251; 10.9%) were most frequently reported. The most frequent drug classes involved were antipsychotics (14,934; 15.5%) and anxiolytics/hypnotics (8,129; 8.4%) and antidepressants (5,776; 6.0%). Failure to follow protocols (n=93), lack of continuity of care (n=92), patient behaviours (n=62) and lack of stock (n=51) were frequently reported as contributory factors associated with moderate, severe and death outcomes. ConclusionMedication incidents pose an enduring threat to patient safety in mental health hospitals. This study has identified important targets which can guide the development of remedial interventions that are tailored to the mental health inpatient setting
New error bounds for Laplace approximation via Stein's method
No full textWe use Stein's method to obtain explicit bounds on the rate of convergence for the Laplace approximation of two different sums of independent random variables; one being a random sum of mean zero random variables and the other being a deterministic sum of mean zero random variables in which the normalisation sequence is random. We make technical advances to the framework of Pike and Ren [38] for Stein's method for Laplace approximation, which allows us to give bounds in the Kolmogorov and Wasserstein metrics. Under the additional assumption of vanishing third moments, we obtain faster convergence rates in smooth test function metrics. As part of the derivation of our bounds for the Laplace approximation for the deterministic sum, we obtain new bounds for the solution, and its first two derivatives, of the Rayleigh Stein equation
Service Research Priorities: Designing Sustainable Service Ecosystems
No full textThis article utilizes input from service scholars, practitioners, reviews of published literature, and influential policy documents to identify service research priorities that push the boundaries of extant research. In a companion piece (Ostrom et al. 2021), we focused on four service research priorities related to managing and delivering service in turbulent times. Further, we identified a set of stakeholder-wants from the literature and included research questions that tie key stakeholder-wants to each of the three priorities in this article and the four priorities in the companion article. Here, we highlight the critical importance of scholarship and practice related to the design of sustainable service ecosystems and discuss three key service research priorities: large-scale and complex service ecosystems for transformative impact (SRP5), platform ecosystems and marketplaces (SRP6), and services for disadvantaged consumers and communities (SRP7). We call for an engaged service scholarship that considers the interrelationships among consumers, organizations, employees, platforms, and societal institutions and pursues transformative goals
High resolution Hα imaging of the Northern Galactic Plane, and the IGAPS images database
No full textThe INT Galactic Plane Survey (IGAPS) is the merger of the optical photometric surveys, IPHAS and UVEX, based on data from the Isaac Newton Telescope (INT) obtained between 2003 and 2018. These capture the entire northern Galactic plane within the Galactic coordinate range, -5<b<+5 deg. and 30<l<215 deg. From the beginning, the incorporation of narrowband H-alpha imaging has been a unique and distinctive feature of this effort. Alongside a focused discussion of the nature and application of the H-alpha data, we present the IGAPS world-accessible database of images for all 5 survey filters, i, r, g, U-RGO and narrowband H-alpha, observed on a pixel scale of 0.33 arcsec and at an effective (median) angular resolution of 1.1 to 1.3 arcsec. The background, noise, and sensitivity characteristics of the narrowband H-alpha filter images are outlined. Typical noise levels in this band correspond to a surface brightness at full one-arcsec resolution of around 2e-16 erg/cm2/s/arcsec2. Illustrative applications of the H-alpha data to planetary nebulae and Herbig-Haro objects are outlined and, as part of a discussion of mosaicking technique, we present a very large background-subtracted narrowband mosaic of the supernova remnant, Simeis 147. Finally we lay out a method that exploits the database via an automated selection of bright ionized diffuse interstellar emission targets for the coming generation of wide-field massive-multiplex spectrographs. Two examples of the diffuse H-alpha maps output from this selection process are presented and compared with previously published data
Model Checking C++ Programs
No full textIn the last three decades, memory safety issues in system programming languages such as C or C++ have been one of the most significant sources of security vulnerabilities. However, there exist only a few attempts with limited success to cope with the complexity of C++ program verification. We describe and evaluate a novel verification approach based on bounded model checking (BMC) and satisfiability modulo theories (SMT) to verify C++ programs. Our verification approach analyzes bounded C++ programs by encoding into SMT various sophisticated features that the C++ programming language oers, such as templates, inheritance, polymorphism, exception handling, and the Standard Template Libraries. We formalize these features within our formal verification framework using a decidable fragment of first-order logic and then show how state-of-the-art SMT solvers can eciently handle that. We implemented our verification approach on top of ESBMC. We compare ESBMC to LLBMC and DIVINE, which are state-of-the-art verifiers to check C++ programs directly from the LLVM bitcode. Experimental results show that ESBMC can handle a wide range of C++ programs, presenting a higher number of correct verification results. Additionally, ESBMC has been applied to a commercial C++ application in the telecommunication domain and successfully detected arithmetic-overflow errors, which could potentially lead to security vulnerabilities
The Dynamics of Immigration and Anti-Immigrant Sentiment in Japan: How and Why Changes in Immigrant share Affect Attitudes towards Immigration in a Newly Diversifying Society
No full textExtensive research investigates how immigration shapes natives’ anti-immigrant sentiment. However, several areas require further scrutiny. This paper explores how processes of immigration affect anti-immigrant sentiment in a new immigration destination country – Japan – drawing on longitudinal data to examine these processes over time, and explicitly testing the mechanisms of perceived-threat and intergroup-contact posited to underpin this relationship. Through this analysis the paper aims to: examine how generalizable the immigrant share/immigration attitudes theoretical framework is to non-Western societies; refine our understanding of the mechanisms underpinning this relationship; and more robustly test its causal assumptions. To pursue these aims the study draws on two sets of nationally-representative Japanese data, designed to generate complementary insights, including: four-waves of longitudinal panel data (2008-2014) and a unique cross-sectional dataset containing measures of perceived-threat and contact. Applying multilevel and fixed-effects panel data approaches, the findings demonstrate that as immigration increases in Japanese prefectures and municipalities, residents become increasingly averse towards immigration (although there is some evidence of non-linearity at the municipality-level, with sentiment improving again in high immigrant share environments). This overall relationship appears largely driven by two competing processes. In higher immigrant share environments, perceived-threat is higher, increasing anti-immigrant sentiment. However, concurrently, intergroup contact also increases in these environments, reducing anti-immigrant sentiment. Therefore, despite the overall negative relationship (driven primarily by perceived-threat), rising contact exerts a countervailing positive effect as immigration increases. Taken together, this research demonstrates that theories of attitudinal-change with higher immigration, developed within Western-contexts, also appear salient for newer-destination, non-Western societies
Assessing the Risk of Resistance to Cationic Biocides incorporating Realism-based and Biophysical Approaches
No full textThe control of microorganisms is a key objective in disease prevention and in medical, industrial, domestic and food-production environments. Whilst the effectiveness of biocides in these contexts is well-evidenced, debate continues about the resistance risks associated with their use. This has driven an increased regulatory burden, which in turn could result in a reduction of both the deployment of current biocides and the development of new compounds and formulas. Efforts to balance risk and benefit are therefore of critical importance and should be underpinned by realistic methods and a multi-disciplinary approach, and through objective and critical analyses of the literature. The current literature on this topic can be difficult to navigate. Much of the evidence for potential issues of resistance generation by biocides is based on either correlation analysis of isolated bacteria, where reports of treatment failure are generally uncommon, or laboratory studies that do not necessarily represent real biocide applications. This is complicated by inconsistencies in the definition of the term resistance. Similar uncertainties also apply to co-resistance between biocides and antibiotics. Risk assessment studies that can better inform practice are required. The resulting knowledge can be utilised by multiple stakeholders including those tasked with new product development, regulatory authorities, clinical practitioners, and the public. This review considers current evidence for resistance and co-resistance and outlines efforts to increase realism in risk assessment. This is done in the background of the discussion of the mode of application of biocides and the demonstrable benefits as well as the potential risks
Potential influence of the microbiome environment in patients with biliary tract cancer and implications for therapy
No full textBiliary tract cancers, including intra- and extra-hepatic cholangiocarcinoma as well as gallbladder cancer, are associated with poor prognosis and the majority of patients present with advanced stage, non-resectable disease at diagnosis. Biliary tract cancer may develop through an accumulation of genetic and epigenetic alterations and can be influenced by microbial exposure. Furthermore, the liver and biliary tract are exposed to the gastrointestinal microbiome through the gut-liver axis. The availability of next generation sequencing technology has led to an increase in studies investigating the relationship between microbiota and human disease. In particular, the interplay between the microbiome, the tumour micro-environment and response to systemic therapy is a prospering area of interest. Given the poor outcomes for patients with biliary tract cancer, this emerging field of research, through which new biomarkers may be identified, offers potential as a tool for early diagnosis, prognostication, or even as a future therapeutic target. This review summarises the available evidence on the microbiome environment in patients with biliary tract cancer, including a discussion around confounding factors, implications for therapy and proposed future directions