Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/ CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31- 0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r2 = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22- 0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD. Copyright © Association for Research in Vision and Ophthalmology.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

A work-based research assessment of the impact of 'lean manufacturing' on health and safety education within an SME

Globalisation has had a major impact on the engineering industry as pacific Rim countries undercut manufacturing costs and provide a more cost-effective location for many businesses. Engineering in Nortehrn Ireland has mostly declined owing to increased competition from these countries. Engineering companies are now forced to streamline their production processes and employ cost-reducing practices in order to meet customer demands at reduced prices. This article aims to analyse the effects of one such streamlining endeavour which was first introduced after World War II in Japan- 'lean manufacturing' . 'Lean manufacturing' aims to reduce all wasteful activities within the production process in order to improve productivity, while reducing manufacturing costs. The work-based project under consideration was concerned with the impact 'lean manufacturing' may have on health and safety performance and education within an engineering company. The focus of the project was to determine through work-based research, and quantitative analysis, the employee perception on health and safety: has it changed (either positively or negatively), as a consequence of implementing 'lean manufacturing'.

A Risky Business: An Examination of Irish Probation Officers Attitudes and Work Practices Regarding Risk Assessment

This article examines recent research on risk assessment and probation practice in Ireland and relates the findings to the ongoing debate regarding risk management practices in probation. The piece discusses current theoretical arguments on the influence of risk in criminal justice and outlines the impact of risk discourse on probation practice in Ireland and England and Wales. Using a mix of qualitative and quantitative methods, Irish probation officers’ attitudes are examined in order to highlight key issues facing probation officers when making risk decisions. These findings are compared and contrasted to other research results from England and Wales. All the conclusions identify both positive and negative consequences of adopting risk tools and point to the continued salience of clinical judgment over actuarial methods of risk assessment. It is argued that the research highlights the role of ‘resistance’ by criminal justice professionals in mediating the effects of the ‘new penology’ at the level of implementation. The idea of resistance holds particular relevance for probation practice in Ireland where professional discretion is maintained within the National Standards framework. Despite this, to date there has been an uncritical approach taken to risk assessment which may ignore the dangers of risk inflation/deflation and the need to take into account local factors in assessing risk of reoffending

Calcification and ossification of the convexity of the falx cerebri and related subdural space in human cadavers

OBJECTIVE: The present work was planned to report the incidence of calcification and ossification of an isolated cranial dural fold. The form, degree of severity and range of extension of such changes will be described. Involvement of the neighboring brain tissue and blood vessels, whether meningeal or cerebral, will also be determined. The results of this study might highlight the occasional incidence of intracranial calcification and ossification in images of the head and their interpretation, by radiologists and neurologists, to be of dural or vascular origin.

METHODS: Two human formalin-fixed cadavers, one middle-aged female another older male, were investigated at the Anatomy Laboratory, College of Medicine, King Faisal University, Dammam, Kingdom of Saudi Arabia during the period from 2000 to 2003. In each cadaver, the skullcap was removed and the convexity of the cranial dura mater, as well as the individual dural folds, were carefully examined for any calcification or ossification. The meningeal and cerebral blood vessels together with the underlying brain were grossly inspected for such structural changes. Calcified or ossified tissues, when identified, were subjected to histological examination to confirm their construction.

RESULTS: The female cadaver showed a calcified parietal emissary vein piercing the skullcap and projecting into the scalp. The latter looked paler and deficient in hair on its right side. The base of the stump was surrounded by a granular patch of calcification. The upper convex border of the falx cerebri was hardened and it presented granules, plaques and a cauliflower mass, which all proved to be osseous in structure. The meningeal and right cerebral vessels were mottled with calcium granules. The underlying temporal and parietal lobes of the right cerebral hemisphere were degenerated. The male cadaver also revealed a calcified upper border of the falx cerebri and superior sagittal sinus. Osseous granules and plaques, similar to those of the first specimen, were also identified but without gross changes in the underlying brain.

CONCLUSION: Calcification or ossification of an isolated site of the cranial dura mater and the intracranial blood vessels might occur. These changes should be kept in mind while interpreting images of the skull and brain. Clinical assessment and laboratory investigations are required to determine whether these changes are idiopathic, traumatic, or as a manifestation of a generalized disease such as hyperparathyroidism, vitamin D-intoxication, or chronic renal failure.

Study on risk assessment and management and prevention of conflicts of interest in the prevention and fight against betting-related match fixing in the EU 28: Final Report

This report concerns the provisions and practices on betting-related match fixing in sports
within the 28 Member States. Carried out in late 2013/early 2014, respondents in each Member
State reported on that state’s gambling-related provisions in respect of football and tennis and
(in each country) a third sport determined on the basis of either its popularity (in terms of
participation or television viewing) or the existence of betting-related “scandals” in that sport
within that particular jurisdiction. Those reports helped the authors to compare the Member
States’ regulatory and self-regulatory frameworks relating to risk assessment and conflict of
interest management, with a view to indicating areas of best practice, identifying particularly
good legislative frameworks and highlighting areas where change was either desirable or
necessary. While some individual Member States have legislation which might provide
templates that others could adapt for their own use, the authors were not convinced that “more
law”, whether at the national or European level, was desirable. Rather, more effective
cooperation among the stakeholders was identified as being more likely to provide tangible
benefits than would new legal frameworks.

Designing for dementia : an assessment of the impact of the physical environment on wayfinding success for residents in long term care settings

It is acknowledged that one of the consequences of the ageing process is cognitive decline, which leads to an increase in the incidence of illnesses such as dementia. This has become ever more relevant due to the projected increase in the ageing demographic. Dementia affects visuo-spatial perception, causing difficulty with wayfinding, even during the early stages of the disease. The literature widely recognises the physical environment’s role in alleviating symptoms of dementia and improving quality of life for residents. It also identifies the lack of available housing options for older people with dementia and consequently the current stock is ill-equipped to provide adequate support.
Recent statistics indicate that 80% of those residing in nursing or residential care homes have some form of dementia or severe memory problems. The shift towards institutional care settings, the need for specialist support and care, places a greater impetus on the need for a person-centred approach to tackle issues related to wayfinding and dementia.
This thesis therefore aims to improve design for dementia in nursing and residential care settings in the context of Northern Ireland. This will be undertaken in order to provide a better understanding of how people with dementia experience the physical environment and to highlight features of the design that assist with wayfinding. Currently there are limited guidelines on design for dementia, meaning that many of these are theoretical, anecdotal and not definitive. Hence a greater verification to address the less recognised design issues is required. This is intended to ultimately improve quality of life, wellbeing, independence and uphold the dignity of people with dementia living in nursing or residential care homes.
The research design uses a mixed methods approach. A thorough preparation and consideration of ethical issues informed the methodology. The various facets were also trialled and piloted to identify any ethical, technological, methodological, data collection and analysis issues. The protocol was then amended to improve or resolve any of the aforementioned issues. Initially a questionnaire based on leading design recommendations was conducted with home managers. Semi-structured interviews were developed from this and conducted with staff and resident’s next of kin. An evidence-based approach was used to design a study which used ethnographic methods, including a wayfinding task. This followed a repeated measures design which would be used to actively engage residents with dementia in the research. Complementary to the wayfinding task, conversational and semi-structured interviews were used to promote dialogue and direct responses with the person with dementia. In addition to this, Space Syntax methodologies were used to examine the physical properties of the architectural layout. This was then cross-examined with interview responses and data from the wayfinding tasks.
A number of plan typologies were identified and were determined as synonymous with decision point types which needed to be made during the walks. The empirical work enabled the synthesis of environmental features which support wayfinding.
Results indicate that particular environmental features are associated with improved performance on the wayfinding tasks. By enhancing design for dementia, through identifying the attributes, challenges with wayfinding may be overcome and the benefits of the physical environment can be seen to promote wellbeing.
The implications of this work mean that the environmental features which have been highlighted from the project can be used to inform guidelines, thus adding to existing knowledge. Future work would involve the dissemination of this information and the potential for it to be made into design standards or regulations which champion design for dementia. These would increase awareness for designers and stakeholders undertaking new projects, extensions or refurbishments.
A person-centred, evidence-based design was emphasised throughout the project which guaranteed an in-depth study. There were limitations due to the available resources, time and funding. Future research would involve testing the identified environmental features within a specific environment to enable measured observation of improvements.