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.

Infrastructure and the Architectures of Modernity in Ireland 1916-2016

At the formation of the new Republic of Ireland, the construction of new infrastructures was seen as an essential element in the building of the new nation, just as the adoption of international style modernism in architecture was perceived as a way to escape the colonial past. Accordingly, infrastructure became the physical manifestation, the concrete identity of these objectives and architecture formed an integral part of this narrative. Moving between scales and from artefact to context, Infrastructure and the Architectures of Modernity in Ireland 1916-2016 provides critical insights and narratives on what is a complex and hitherto overlooked landscape, one which is often as much international as it is Irish. In doing so, it explores the interaction between the universalising and globalising tendencies of modernisation on one hand and the textures of local architectures on the other.

The book shows how the nature of technology and infrastructure is inherently cosmopolitan. Beginning with the building of the heroic Shannon hydro-electric facility at Ardnacrusha by the German firm of Siemens-Schuckert in the first decade of independence, Ireland became a point of varying types of intersection between imported international expertise and local need. Meanwhile, at the other end of the century, by the year 2000, Ireland had become one of the most globalized countries in the world, site of the European headquarters of multinationals such as Google and Microsoft. Climatically and economically expedient to the storing and harvesting of data, Ireland has subsequently become a repository of digital information farmed in large, single-storey sheds absorbed into anonymous suburbs. In 2013, it became the preferred site for Intel to design and develop its new microprocessor chip: the Galileo. The story of the decades in between, of shifts made manifest in architecture and infrastructure from the policies of economic protectionism, to the opening up of the country to direct foreign investment and the embracing of the EU, is one of the influx of technologies and cultural references into a small country on the edges of Europe as Ireland became both a launch-pad and testing ground for a series of aspects of designed modernity.

Periodontal Manifestations of Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE) Syndrome in an 11 Year Old Patient

Introduction: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) is an auto inflammatory syndrome caused by an autosomal recessive gene mutation. This very rare syndrome has been reported in only 14 patients worldwide. A number of clinical signs have been reported including joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced childhood lipodystrophy. Further symptoms include recurrent fevers, purpuric skin lesions, periorbital erythema and failure to thrive. This is the first reported case of periodontal manifestations associated with CANDLE syndrome. 
Case Presentation: An 11 year old boy was referred to Cork University Dental School and Hospital with evidence of severe periodontal destruction. The patient’s medical condition was managed in Great Ormond Street Children’s Hospital, London. The patient’s dental management included initial treatment to remove teeth of hopeless prognosis followed by prosthodontic rehabilitation using removable partial dentures. This was followed by further non-surgical periodontal treatment and maintenance. In the long term, the potential definitive restorative options, including dental implants, will be evaluated in discussion with the patient’s medical team.
Conclusion: Periodontitis as a manifestation of systemic disease is one of seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system. A number of systemic diseases have been associated with advanced periodontal destruction including Diabetes Mellitus, Leukaemia and Papillon-Lefevre Syndrome. In the case described, treatment necessitated a multidisciplinary approach with input from medical and dental specialities for a young patient with severe periodontal destruction associated with CANDLE syndrome.

Infra-Éireann: Making Ireland Modern - Irish Pavilion for the 14th Architectural biennale, Venice 2014.

After an open competition, we were selected to commission, curate and design the Irish pavilion for the Venice biennale 2014. Our proposal engage with the role of infrastructure and architecture in the cultural development of the new Irish state 1914-2014. This curatorial programme was realised in a demountable, open matrix pavilion measuring 12 x 5 x 6 metres.

How modernity is absorbed into national cultures usually presupposes an attachment to previous conditions and a desire to reconcile the two. In an Irish context, due to the processes of de-colonisation and political independence, this relationship is more complicated.

In 1914, Ireland was largely agricultural and lacked any significant industrial complex. The construction of new infrastructures after independence in 1921 became central to the cultural imagining of the new nation. The adoption of modernist architecture was perceived as a way to escape the colonial past. As the desire to reconcile cultural and technological aims developed, these infrastructures became both the physical manifestation and concrete identity of the new nation with architecture an essential element in this construct.

Technology and infrastructure are inherently cosmopolitan. Beginning with the Shannon hydro-electric facility at Ardnacrusha (1929) involving the German firm of Siemens-Schuckert, Ireland became a point of various intersections between imported international expertise and local need. By the turn of the last century, it had become one of the most globalised countries in the world, site of the European headquarters of multinationals such as Google and Microsoft. Climatically and economically expedient to the storing and harvesting of data, Ireland has subsequently become an important repository of digital information farmed in large, single-storey sheds absorbed into dispersed suburbs. In 2013, it became the preferred site for Intel to design and develop its new microprocessor board, the Galileo, a building block for the internet of things.

The story of the decades in between, of shifts made manifest in architecture and infrastructure, from the policies of economic protectionism to the embracing of the EU is one of the influx of technologies and cultural references into a small country on the edges of Europe: Ireland as both a launch-pad and testing ground for a series of aspects of designed modernity.

The Muslim Brotherhood: the Arab Spring its Future Face

The Muslim Brotherhood is the most significant and enduring Sunni Islamist organization of the contemporary era. Its roots lie in the Middle East but it has grown into both a local and global movement, with its well-placed branches reacting effectively to take the opportunities for power and electoral competition offered by the Arab Spring.

Regarded by some as a force of moderation among Islamists, and by others as a façade hiding a terrorist fundamentalist threat, the potential influence of the Muslim Brotherhood on Middle Eastern politics remains ambiguous.The Muslim Brotherhood: The Arab Spring and its Future Face provides an essential insight into the organisation, with chapters devoted to specific cases where the Brotherhood has important impacts on society, the state and politics. Key themes associated with the Brotherhood, such as democracy, equality, pan-Islamism, radicalism, reform, the Palestine issue and gender, are assessed to reveal an evolutionary trend within the movement since its founding in Egypt in 1928 to its manifestation as the largest Sunni Islamist movement in the Middle East in the 21st century. The book addresses the possible future of the Muslim Brotherhood; whether it can surprise sceptics and effectively accommodate democracy and secular trends, and how its ascension to power through the ballot box might influence Western policy debates on their engagement with this manifestation of political Islam.

Drawing on a wide range of sources, this book presents a comprehensive study of a newly resurgent movement and is a valuable resource for students, scholars and policy makers focused on Middle Eastern Politics.

Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation

Cystic fibrosis (CF) is a lifelong, inflammatory multi-organ disease and the most common lethal, genetic condition in Caucasian populations, with a median survival rate of 41.5 years. Pulmonary disease, characterized by infective exacerbations, bronchiectasis and increasing airway insufficiency is the most serious manifestation of this disease process, currently responsible for over 80% of CF deaths. Chronic dysregulation of the innate immune and host inflammatory response has been proposed as a mechanism central to this genetic condition, primarily driven by the nuclear factor κB (NF-κB) pathway. Chronic activation of this transcription factor complex leads to the production of pro-inflammatory cytokines and mediators such as IL-6, IL-8 and TNF-α. A20 has been described as a central and inducible negative regulator of NF-κB. This intracellular molecule negatively regulates NF-κB-driven pro-inflammatory signalling upon toll-like receptor activation at the level of TRAF6 activation. Silencing of A20 increases cellular levels of p65 and induces a pro-inflammatory state. We have previously shown that A20 expression positively correlates with lung function (FEV1%) in CF. Despite improvement in survival rates in recent years, advancements in available therapies have been incremental. We demonstrate that the experimental use of naturally occurring plant diterpenes such as gibberellin on lipopolysaccharide-stimulated cell lines reduces IL-8 release in an A20-dependent manner. We discuss how the use of a novel bio-informatics gene expression connectivity-mapping technique to identify small molecule compounds that similarly mimic the action of A20 may lead to the development of new therapeutic approaches capable of reducing chronic airway inflammation in CF. 

Integrative analysis of chemo-transcriptomic profiles for drug-feature specific gene expression signatures

One of the major challenges in systems biology is to understand the complex responses of a biological system to external perturbations or internal signalling depending on its biological conditions. Genome-wide transcriptomic profiling of cellular systems under various chemical perturbations allows the manifestation of certain features of the chemicals through their transcriptomic expression profiles. The insights obtained may help to establish the connections between human diseases, associated genes and therapeutic drugs. The main objective of this study was to systematically analyse cellular gene expression data under various drug treatments to elucidate drug-feature specific transcriptomic signatures. We first extracted drug-related information (drug features) from the collected textual description of DrugBank entries using text-mining techniques. A novel statistical method employing orthogonal least square learning was proposed to obtain drug-feature-specific signatures by integrating gene expression with DrugBank data. To obtain robust signatures from noisy input datasets, a stringent ensemble approach was applied with the combination of three techniques: resampling, leave-one-out cross validation, and aggregation. The validation experiments showed that the proposed method has the capacity of extracting biologically meaningful drug-feature-specific gene expression signatures. It was also shown that most of signature genes are connected with common hub genes by regulatory network analysis. The common hub genes were further shown to be related to general drug metabolism by Gene Ontology analysis. Each set of genes has relatively few interactions with other sets, indicating the modular nature of each signature and its drug-feature-specificity. Based on Gene Ontology analysis, we also found that each set of drug feature (DF)-specific genes were indeed enriched in biological processes related to the drug feature. The results of these experiments demonstrated the pot- ntial of the method for predicting certain features of new drugs using their transcriptomic profiles, providing a useful methodological framework and a valuable resource for drug development and characterization.

Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies.