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Introduction: Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse. Methods: We conducted a cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of 2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR 2), albuminuria (albumin-to-creatinine ratio [ACR] >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes. Results: A total of 2864 participants (mean age 48.1 [SD 10.3], 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio [OR] 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes. Conclusion: APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.

The emergence of new SARS-COV-2 variants is of public health concern in case of vaccine escape. Described are three patients with advanced HIV-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations which are associated with increased transmissibility and immune escape.

The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is of public health concern in case of vaccine escape. Described are 3 patients with advanced human immunodeficiency virus (HIV)-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations that are associated with increased transmissibility and immune escape.

Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.The primary outcome was estimated glomerular filtration rate (eGFR) 60 ml/min per 1.73 mA total of 2895 participants (mean age 48.1 [SD 10.3], 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR 60 ml/min per 1.73 mOur results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with

A 60-year-old gentleman presented with chronic diarrhoea and weight loss. Following an array of investigations, primarily targeting a possible malignancy, gastritis and duodenitis were observed on endoscopy. Gastric and duodenal biopsies showed aggregates of PAS positive macrophages in the lamina propria. Polymerase chain reaction confirmed the presence of Whipple's disease (WD). WD is a rare multisystemic granulomatous infectious disorder, affecting many organ systems but predominantly the gastrointestinal system. WD has a two stage process. The prodromal stage is dominated by arthralgia and arthritis, followed by a latency period, from one to ten years and then by a later steady-state stage which is characterized by the involved organ systems. WD can be fatal if left untreated, however a strict antibiotic regime may eradicate the causative organism, Tropheryma whipplei. We report a rare case of WD diagnosed on a gastric biopsy with an agglomeration of misleading signs and symptoms which demonstrate the mimicry of this potential infectious disease.

As a single coherent model, the proposed Virtual Historic Dublin City will improve the current approaches for planning, conserving, presenting and interpreting cultural heritage buildings and their environments. The combination of digital recording, modelling and data management systems enable the interaction with complex, interlinked three-dimensional structures containing rich and diverse underlying data. End users can encompass architectural and engineering conservation, education and research, in addition to public engagement and cultural tourism. In this paper a digital design framework is presented, based on state of the art current approaches for recording, modelling and presenting Virtual Historic Dublin. The modelling sites and structures is based on remotely sensed survey data which is processed and modelled in Historic BIM or GIS allowing the addition of semantic attributes. Archiving and storage of both models and knowledge and information attributes requires open systems and server data base capable of handling vector and point cloud information in addition to other digital data. The dissemination and interaction with the models and attached knowledge attributions is based on combining game engine platforms, Historic BIM, Historic GIS and access to compatible storage and data base.

This paper proposes a design for libraries of European Classical architectural elements based on shape grammars. This design is based on a workflow which develops library objects from 3D CAD primitives using architectural rules to construct parametric representations of architectural elements. In the case of Classical architecture, the design and detail for the parametric objects are based on manuscripts ranging from Vitruvius to Palladio to the architectural pattern books of the eighteenth century. The generation of 3D objects for virtual reconstruction necessitates the application of computer algorithms and rules introduced by the user to generate objects, buildings and spaces from a grammar and vocabulary of shapes. Both the use of graphicly constructed and coded parametric libraries in formal and open-source platforms will be considered here.

The change and restrictions in how we react with cultural heritage because of the COVID-19 pandemic has created an urgency in advancing remote and digital access to objects and sites. This paper outlines the process for developing Virtual Learning Environments (VLEs) using digital recording and modelling of architectural heritage and archaeology. Virtual Reality (VR) software, game engine platforms and WEB platforms are outlined which can be applied to represent heritage sites in addition to emerging screen based technological learning systems. The application Historic Building Information Modelling (HBIM) and Game Engine Platforms for creating Virtual Learning Environments (VLEs) is also examined. The design-theory based on Virtual Learning Objects for cultural heritage is explored. Two case studies are explored for their potential to create Virtual Heritage Learning Environments. Finally, a design framework is proposed for developing Virtual Heritage Learning Environments.

Key Clinical Message CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

Cultural heritage researchers have recently begun applying Building Information Modelling (BIM) to historic buildings. The model is comprised of intelligent objects with semantic attributes which represent the elements of a building structure and are organised within a 3D virtual environment. Case studies in Ireland are used to test and develop the suitable systems for (a) data capture/digital surveying/processing (b) developing library of architectural components and (c) mapping these architectural components onto the laser scan or digital survey to relate the intelligent virtual representation of a historic structure (HBIM). While BIM platforms have the potential to create a virtual and intelligent representation of a building, its full exploitation and use is restricted to narrow set of expert users with access to costly hardware, software and skills. The testing of open BIM approaches in particular IFCs and the use of game engine platforms is a fundamental component for developing much wider dissemination. The semantically enriched model can be transferred into a WEB based game engine platform.

In this paper the recording and design for a Virtual Reality Immersive Model of Armagh Observatory is presented, which will replicate the historic buildings and landscape with distant meridian markers and position of its principal historic instruments within a model of the night sky showing the position of bright stars. The virtual reality model can be used for educational purposes allowing the instruments within the historic building model to be manipulated within 3D space to demonstrate how the position measurements of stars were made in the 18th century. A description is given of current student and researchers activities concerning on-site recording and surveying and the virtual modelling of the buildings and landscape. This is followed by a design for a Virtual Reality Immersive Model of Armagh Observatory use game engine and virtual learning platforms and concepts.

In an extensive review of existing literature a number of observations were made in relation to the current approaches for recording and modelling existing buildings and environments: Data collection and pre-processing techniques are becoming increasingly automated to allow for near real-time data capture and fast processing of this data for later modelling applications. Current BIM software is almost completely focused on new buildings and has very limited tools and pre-defined libraries for modelling existing and historic buildings. The development of reusable parametric library objects for existing and historic buildings supports modelling with high levels of detail while decreasing the modelling time. Mapping these parametric objects to survey data, however, is still a time-consuming task that requires further research. Promising developments have been made towards automatic object recognition and feature extraction from point clouds for as-built BIM. However, results are currently limited to simple and planar features. Further work is required for automatic accurate and reliable reconstruction of complex geometries from point cloud data. Procedural modelling can provide an automated solution for generating 3D geometries but lacks the detail and accuracy required for most as-built applications in AEC and heritage fields.

Background: Invasive lobular carcinoma (ILC) is characterized by an infiltrative discohesive growth pattern, making it difficult to accurately assess both clinically and by imaging studies. Despite favourable biological characteristics, challenges remain in the surgical treatment of ILC. We aimed to evaluate radiology/histology concordance and identify histological and biological parameters on core biopsies that may predict final tumour histology and guide surgical treatment decisions. Patients and Methods: The radiology and histology reports for all newly diagnosed cases of ILC were analysed. The biopsy and resection histological slides for all the surgical cases were reviewed. Results: 75 new cases of ILC were diagnosed over a 2-year period. 48 patients underwent surgery of whom 25% had 2 or more operations. There was discordance between radiological and histological tumour focality and tumour size in 35 and 40%, respectively. The correlation between radiology/histology discordance and E-cadherin expression was statistically significant. However, the correlation between radiology/histology discordance and menopausal status, breast density, pattern of invasion, presence of lobular intraepithelial neoplasia (LIN), hormonal status, and Ki67 were not statistically significant. Conclusion: Histological and biological factors in ILC, with the exception of E-cadherin expression, do not seem to play a significant role in radiology/histology discordance. However, larger studies are needed to further corroborate these findings.

This paper illustrates how BIM integration with GIS is approached as part of the workflow in creating Virtual Historic Dublin. A design for a WEB based interactive 3D model of historic buildings and centres in Dublin City (Virtual Historic Dublin City) paralleling smart city initiates is now under construction and led by the National Monuments at the Office of Public Works in Ireland. The aim is to facilitate the conservation and maintenance of historic infrastructure and fabric and the dissemination of knowledge for education and cultural tourism using an extensive Historic Building Information Model. Remote sensing data is now processed with greater ease to create 3D intelligent models in Historic BIM. While the use of remote sensing, HBIM and game engine platforms are the main applications used at present, 3D GIS has potential to form part of the workflow for developing the Virtual Historic City. 2D GIS is now being replaced by 3D spatial data allowing more complex analysis to be carried out, 3D GIS can define and depict buildings, urban rural centres in relation to their geometry topological, semantic and visualisation properties. The addition of semantic attributes allows complex analysis and 3D spatial queries for modelling city and urban elements. This analysis includes fabric and structural elements of buildings, relief, vegetation, transportation, water bodies, city furniture and land use.

Historic Building Information Modelling (HBIM) is a new approach for modelling historic buildings which develops full Building Information Models (BIMs) from remotely sensed data. HBIM consists of a novel library of reusable parametric objects, based on historic architectural data and a system for mapping theses library objects to survey data. This chapter describes the development of a library of parametric objects for HBIM that can be used to model classical architectural elements. Steps towards automating the HBIM process are also described in this chapter. Using concepts from procedural modelling, a new set of rules and algorithms have been developed to automatically combine HBIM library objects and generate different building arrangements by altering parameters. This is a semi-automatic process where the required building structure and objects are first automatically generated and then refined to match survey data. The use of procedural modelling techniques with HBIM library objects introduces automation and speeds up the slow process of plotting library objects to survey data.

Patients with sentinel lymph node (SLN) metastases may not require axillary lymph node dissection (ALND) but it remains unclear if patients with a positive ultrasound-guided axillary core biopsy (ACB) would satisfy such criteria. The aim of this study was to assess if breast cancer patients with a positive pre-operative ACB have more aggressive tumour characteristics/higher axillary nodal burden compared to those with a positive SLN. Data was extracted from a prospectively maintained breast cancer database between 2012 and 2015. Patients who underwent ALND after either positive ACB or SLN were included and tumour characteristics/nodal burden were compared. One hundred eighty patients underwent ALND, 125/180 after positive ACB and 55/180 after positive SLNB. Patients with positive ACB were more likely to undergo mastectomy (chi-square test; p = 0.03) and have higher tumour grades (Mann-Whitney test; p

We report a case of a 79-year-old gentleman who presented to the emergency department with a 5-day history of abdominal pain, constipation, a progressively distending abdomen and new onset feculent vomiting on a background of a recent endoscopic decompression of a sigmoid volvulus. Investigations confirmed the presence of a recurrent sigmoid volvulus. Attempts to reduce this endoscopically failed and laparotomy with sub-total colectomy and ileostomy formation was performed. Histology from the resected specimen identified a distinct pathology, namely intestinal lipofuscinosis also known as brown bowel syndrome. Brown bowel syndrome is a recognized but rare complication of chronic long term malnutrition. It may present in a myriad of ways including atonia and, rarely, massive colonic dilatation, as in our case.

In this paper the current findings to date of the Historic Building Information Model (HBIM) of the Four Courts in Dublin are presented. The Historic Building Information Model (HBIM) forms the basis for both structural and conservation analysis to measure the impact of war damage which still impacts on the building. The laser scan survey was carried out in the summer of 2014 of the internal and external structure. After registration and processing of the laser scan survey, the HBIM was created of the damaged section of the building and is presented as two separate workflows in this paper. The first is the model created from historic data, the second a procedural and segmented model developed from laser scan survey of the war damaged drum and dome. From both models structural damage and decay simulations will be developed for documentation and conservation analysis.

This article is written in response to the linked editorial by Dr Geraghty about the adaptive Pacing, graded Activity and Cognitive behaviour therapy; a randomised Evaluation (PACE) trial, which we led, implemented and published. The PACE trial compared four treatments for people diagnosed with chronic fatigue syndrome. All participants in the trial received specialist medical care. The trial found that adding cognitive behaviour therapy or graded exercise therapy to specialist medical care was as safe as, and more effective than, adding adaptive pacing therapy or specialist medical care alone. Dr Geraghty has challenged these findings. In this article, we suggest that Dr Geraghty’s views are based on misunderstandings and misrepresentations of the PACE trial; these are corrected.

Ireland has one of the highest levels of alcohol consumption in the EU, consuming 10.6 litres of pure alcohol per person in 2003, and increasing to 13.4 litres in 2006. This rise in consumption has led to increases in alcohol-related harm and disease, and has resulted in more than 1,775 deaths according to the Health Research Board (Mongan, et al. 2007). In general, increases in overall consumption are accompanied by a greater incidence of health and social problems. In addition to the high volume of alcohol consumed by people in Ireland, drinking occasions appear to be strongly related to heavy episodic or “binge” drinking patterns. Binge drinking is defined as drinking five or more drinks in a row for men and four or more drinks in a row for women, at least once in the previous two weeks (Dantzer, et al. 2006). The prevalence of alcohol use and associated problems is higher in college populations than in the general public (Evans and Dunn, 1995). In fact, binge drinking has been identified as the number one substance abuse problem in university life (Syre, et al. 1997). A recent international study of drinking among university students in 21 countries found that Ireland had the highest proportions of male and female heavy or binge drinkers (Dantzer, et al. 2006). Women are at an increased risk from alcohol use because they need less alcohol per kilogram of body weight than men to attain the same peak blood alcohol level and level of impairment (Rohsenow, 1998). In their recent report, The Health Research Board (2007) in Ireland state that “if current trends continue, we will see significantly higher numbers of middle-aged women experiencing alcohol-related morbidity or greater premature mortality”.

In today’s society, blood donation is dependent on the goodwill of people to voluntarily donate blood without financial reward. There is a continuous need for new blood donors, because the demand for donor blood is increasing, whereas the supply of blood is declining. Three thousand blood donations are needed in the Republic of Ireland every week. Maintaining an adequate supply is the biggest challenge. Only 3.6% of the eligible population in the Republic of Ireland donate blood. This leaves an enormous potential blood donor base, which if tapped into and maintained could lead to an adequate reserve of donations to meet the transfusion needs of Ireland (Harrington et al. 2007). Research results from the Council of Europe (Van der Poel et al. 2007) found that the average number of donors in relation to the general population in Europe is 25 per 1,000 inhabitants. Ireland is slightly above this with 29.7 donors per 1,000 inhabitants. Repeat donors are the key individuals to maintaining a safe and sufficient blood supply (Schreiber et al. 2003), which is paramount as one in four individuals will require a blood transfusion at some stage in their lives (IBTS, 2007). Glynn et al. (2002) have identified several motivators for blood donation including altruism, awareness of the need for blood in the community, a sense of social obligation or duty, personal social pressure, the need to replace blood used by a friend or relative, and increased self esteem. Various reasons have been cited for avoiding blood donation. Fears about the collection process are the most prevalent (Gillespie and Hillyer, 2002). These include fear of needles, general apprehension, negative feelings about the sight of blood, concern about pain or bruising and anxiety that mistakes could be made during donation. Fear of adverse physiological reactions such as weakness or fatigue, dizziness, nausea, or fainting complicate the blood collection process, and are a significant disincentive for repeat donation (France et al. 2005). Kolins and Herron, (2003) propose that the way forward to achieve growth in blood donor numbers lies with a market-type approach with targeted marketing campaigns to profiled young people.

It is estimated that tobacco use is responsible for more than 500,000 deaths every year across the EU (Ryan, 2000). In adolescence, higher rates of smoking are reported among girls than boys in an increasing number of European countries (Currie et al. 2004). Estimates by the World Health Organisation calculate that the number of women who smoke is set to almost triple on a global scale by the year 2025. This trend has also been confirmed in Europe. While men’s smoking is slowly on the decline, smoking rates among women increased in 11 of the 25 EU member states between 1985 and 2003 (European Network for Smoking Prevention, 2007). The Irish Office of Tobacco Control’s research has confirmed that initiation into smoking is largely a childhood phenomenon. More than 75% of all smokers in Ireland started to smoke before they reached the age of 18 (HBSC Ireland, 2006). The tobacco industry needs 50 Irish children to start smoking every day in order to maintain the size of its current Irish customer base (Office of Tobacco Control, 2007). The Irish National Health and Lifestyle survey 2002 states that almost half of Irish children have tried a cigarette. By the age of 15 to 17 years, one third of all boys and girls are smoking between three and six cigarettes a day. By the age of 15 years, more girls smoke than boys and by the age of 16 years, 80% of all smokers have become addicted. Smoking plays an important role in the social and physical environment of young people. Often young smokers, although aware of the health risks, minimise these risks for themselves, underestimate the risk of becoming addicted and do not relate their personal smoking to adult smoking behaviours (Lambert et al. 2002). The use of fear appeals is perhaps the most common tactic for social marketing, with threats of physical harm including injury and death used more frequently than social threats. The prevailing anti-tobacco appeal attempts to scare the target group into attitude and behaviour changes through the use of physical or social threat messages. According to the theory, people can be motivated to engage in desirable health behaviours not only to avoid health risks (physical threats) but also to avoid social or interpersonal risks (Dijkstra, et al. 1998). In a smoking context, studies have shown that an overall decline in smoking behaviour was noticed by adolescents who viewed an anti-smoking advertisement as opposed to adolescents who did not view an anti-smoking advertisement (Smith and Stutts, 2003).

This paper outlines a new approach for generating digital heritage models from laser scan or photogrammetric data using Historic Building Information Modelling (HBIM). HBIM is a plug-in for Building Information Modelling (BIM) software that uses parametric library objects and procedural modelling techniques to automate the modelling stage. The HBIM process involves a reverse engineering solution whereby parametric interactive objects representing architectural elements are mapped onto laser scan or photogrammetric survey data. A library of parametric architectural objects has been designed from historic manuscripts and architectural pattern books. These parametric objects were built using an embedded programming language within the ArchiCAD BIM software called Geometric Description Language (GDL). Procedural modelling techniques have been implemented with the same language to create a parametric building façade which automatically combines library objects based on architectural rules and proportions. Different configurations of the façade are controlled by user parameter adjustment. The automatically positioned elements of the façade can be subsequently refined using graphical editing while overlaying the model with orthographic imagery. Along with this semi-automatic method for generating façade models, manual plotting of library objects can also be used to generate a BIM model from survey data. After the 3D model has been completed conservation documents such as plans, sections, elevations and 3D views can be automatically generated for conservation projects.

Historic Building Information Modelling (HBIM) is a novel prototype library of parametric objects, based on historic architectural data and a system of cross platform programmes for mapping parametric objects onto point cloud and image survey data. The HBIM process begins with remote collection of survey data using a terrestrial laser scanner combined with digital photo modelling. The next stage involves the design and construction of a parametric library of objects, which are based on the manuscripts ranging from Vitruvius to 18th century architectural pattern books. In building parametric objects, the problem of file format and exchange of data has been overcome within the BIM ArchiCAD software platform by using geometric descriptive language (GDL). The plotting of parametric objects onto the laser scan surveys as building components to create or form the entire building is the final stage in the reverse engineering process. The final HBIM product is the creation of full 3D models including detail behind the object’s surface concerning its methods of construction and material make-up. The resultant HBIM can automatically create cut sections, details and schedules in addition to the orthographic projections and 3D models (wire frame or textured) for both the analysis and conservation of historic objects, structures and environments.

BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments. METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094. FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p

Historic Building Information Modelling (HBIM) is a novel prototype library of parametric objects based on historic data and a system of cross platform programmes for mapping parametric objects onto a point cloud and image survey data. The HBIM process begins with remote collection of survey data using a terrestrial laser scanner combined with digital photo modelling. The next stage involves the design and construction of a parametric library of objects, which are based on the manuscripts ranging from Vitruvius to 18th century architectural pattern books. In building parametric objects, the problem of file format and exchange of data has been overcome within the BIM ArchiCAD software platform by using geometric descriptive language (GDL). The plotting of parametric objects onto the laser scan surveys as building components to create or form the entire building is the final stage in the reverse engin- eering process. The final HBIM product is the creation of full 3D models including detail behind the object's surface concerning its methods of construction and material make-up. The resultant HBIM can automatically create cut sections, details and schedules in addition to the orthographic projections and 3D models (wire frame or textured).

To determine whether gene expression profiling could improve outcome prediction in children with acute lymphoblastic leukemia (ALL) at high risk for relapse, we profiled pretreatment leukemic cells in 207 uniformly treated children with high-risk B-precursor ALL. A 38-gene expression classifier predictive of relapse-free survival (RFS) could distinguish 2 groups with differing relapse risks: low (4-year RFS, 81%, n = 109) versus high (4-year RFS, 50%, n = 98; P < .001). In multivariate analysis, the gene expression classifier (P = .001) and flow cytometric measures of minimal residual disease (MRD; P = .001) each provided independent prognostic information. Together, they could be used to classify children with high-risk ALL into low- (87% RFS), intermediate- (62% RFS), or high- (29% RFS) risk groups (P < .001). A 21-gene expression classifier predictive of end-induction MRD effectively substituted for flow MRD, yielding a combined classifier that could distinguish these 3 risk groups at diagnosis (P < .001). These classifiers were further validated on an independent high-risk ALL cohort (P = .006) and retainedindependent prognostic significance (P < .001) in the presence of other recently described poor prognostic factors (IKAROS/IKZF1 deletions, JAK mutations, and kinase expression signatures). Thus, gene expression classifiers improve ALL risk classification and allow prospective identification of children who respond or fail current treatment regimens. These trials were registered at http://clinicaltrials.gov under NCT00005603.

PurposeThe purpose of this research is to outline in detail the procedure of remote data capture using laser scanning and the subsequent processing required in order to identify a new methodology for creating full engineering drawings (orthographic and 3D models) from laser scan and image survey data for historic structures.Design/methodology/approachHistoric building information modelling (HBIM) is proposed as a new system of modelling historic structures; the HBIM process begins with remote collection of survey data using a terrestrial laser scanner combined with digital cameras. A range of software programs is then used to combine the image and scan data.FindingsMeshing of the point cloud followed by texturing from the image data creates a framework for the creation of a 3D model. Mapping of BIM objects onto the 3D surface model is the final stage in the reverse engineering process, creating full 2D and 3D models including detail behind the object's surface concerning its methods of construction and material makeup, this new process is described as HBIM.Originality/valueThe future research within this area will concentrate on three main stands. The initial strand is to attempt improve the application of geometric descriptive language to build complex parametric objects. The second stand is the development of a library of parametric based on historic data (from Vitruvius to 18th century architectural pattern books). Finally, while it is possible to plot parametric objects onto the laser scan data, there is need to identify intermediate software platforms to accelerate this stage within the HBIM framework.

Skin cancer is the most common cancer in Ireland and worldwide. Skin cancer rates have been steadily rising in recent times. In Ireland, one in every eight men and one in every ten women will develop skin cancer by the age of 74 years. Two thirds of Irish people have a higher risk of developing skin cancer because of their fair skin type. This paper focuses on the use of social marketing to educate people on the dangers of skin cancer with the eventual aim of making recommendations to aid in its prevention. In-depth interviews were conducted with ten leading personnel from skin cancer and social marketing fields. All interviewees reached similar conclusions suggesting that one clear understandable message on the Vitamin D controversy is vital, as well as the importance of not only parental role models for children but role models in general to alter faulty sun protective behaviours. All interviewees agreed on the dangers of mixed messaging within skin cancer and other health promotion campaigns where there is a serious danger of campaign literature being completely disregarded due to inconsistent messaging. This necessitates the creation of cross functional campaigns where government agencies work in conjunction with each other to promote consistent health messages to the public. Segmentation was also identified as a key contributor to successfully reaching each audience effectively; messages must be tailored for each specific audience. The study further argues the importance of working with the Irish government to enact legislation banning sunbeds.

Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

The ideal farmhouse cheese profile for 256 Irish farmhouse cheese consumers was one with a strong flavour, a hard texture, a wax packaged wheel, made with pasteurised milk, nutritional information present on the package, a white coloured cheese and a price of €3.17 per 200g. Least squares regression was used to estimate part worths for the conjoint analysis. A cluster analysis revealed there were two clusters with different ideal product profiles. Cluster one preferred cheese made with pasteurised milk, while cluster two preferred one made with unpasteurised milk. Market simulation experiments simulated market shares for nine products (six semi‐hard farmhouse cheeses, one soft farmhouse cheese and two factory cheeses), as well as the ideal product profiles for each cluster (two in total). The “ideal” product profile for each cluster was identified as having the largest market share, under both models of analysis.

Guidelines for commencing therapy for HIV infection have been based upon HIV-1 RNA and CD4 lymphocyte thresholds. The influence of confounding factors such as gender, ethnicity and co-infections is unproven.To analyse ethnic discordance in plasma HIV-1 viral load (VL) and CD4+ count and its potential clinical significance in Black and Caucasian groups.Retrospective, cross-sectional, observational study of 537 antiretroviral nai;ve HIV-1-positive individuals attending two East London clinics. Baseline data were obtained from individuals who registered at the clinic from November 1996 to August 1999. An analysis was performed comparing ethnic differences in plasma HIV-1 VL, CD4+ count, CD8+ count, co-infections, CDC disease category, AIDS-defining illnesses and mode of transmission.Plasma HIV-1 VL was significantly lower in Blacks (4.5 copies/ml versus 4.7 copies/ml; P0.05) despite lower baseline CD4+ counts and similar rates of disease progression to Caucasian groups. This association remained for patients with less advanced disease after stratification for CD4+ count (CD4+ 200-500, VL 4.5 copies/ml versus 4.7 copies/ml, P0.01; CD4+500, VL 3.4 copies/ml versus 4.3 copies/ml, P0.001) and disease category (non-AIDS, 4.4 copies/ml versus 4.7 copies/ml; P0.005). On multivariate analysis, the association persisted following adjustment for gender, age, co-infections, CD4+ count and mode of transmission.These results suggest that plasma HIV-1 VL is discordantly low in Black compared with Caucasian groups stratified for CD4+ count, in this cohort of antiretroviral nai;ve HIV-1-positive individuals living in London. Although there are a number of possible explanations for this finding, it has considerable clinical relevance for the management of Black HIV-1-infected patients within UK, with significant implications for the decision about when to commence antiretroviral or immune-based therapies.

Automated systems using terrestrial laser scanning and digital photogrammetry for recording of historic structures produce accurate 3D surface modelling of historic structures or artefacts, but do not supply detail behind the surface of the scan. Correlation of laser-scan and image survey data with historic documentation will augment the surface detail of the laser scan survey. Architectural pattern books published during the 1700s were one of the main inspirational sources for the design of vernacular eighteenth-century classical buildings. The main aim of this chapter is to describe the process of correlation of laser-scan and image survey data with historic detail from architectural pattern books, and secondly the resultant analysis of the systems of geometrical proportioning used in the design and building of eighteenth-century vernacular classical buildings in Ireland.

The ideal honey profile for 153 Irish consumers of honey was one with a thick texture, a dark golden colour, made by a small‐scale producer, at a price of IR£1.95 and packaged in a 454g (1lb) plain glass jar. Least squares regression was used to estimate part worths for the conjoint analysis. Using the scale attribute as a basis for segmentation three distinct segments were identified. Market simulation experiments simulated market shares for 11 products; the ideal products for each segment (three in total), two existing mass‐produced honeys, four from small‐scale local farm producers and one from a farm producer produced on a larger scale. The first cluster was the least price sensitive, with the most important attribute being small‐scale producer source. Mass‐produced honeys had a very small market share in this segment. The second cluster was distinguished by deriving a high utility from a light‐coloured honey. Again mass‐produced honeys had the smallest market share. In the first two clusters, in addition to some of the ideal products, honey/s from small‐scale producers had high market shares. The third cluster was the most price sensitive and the mass‐produced honeys commanded their largest market share in this segment. This segment also derived the highest utility of all segments from a honey produced on a mass scale. The results show that adjusting pricing and promotional approaches could increase market share for honey producers.

We measured plasma levels of all the antioxidant-micronutrients in subjects with HIV infection and controls. Plasma levels of all the carotenoids, including lutein, cryptoxanthin, lycopene, alpha-carotene and beta-carotene as well as vitamins A, C and E and cholesterol were assayed in 35 subjects with HIV infection and 38 controls. We found a significant depletion of all the carotenoids (P < 0.001) and vitamin C (P < 0.01) and cholesterol (P < 0.001) but not vitamins A or E in HIV-infected subjects. Further analysis of the HIV-infected subjects revealed that plasma levels of 4 of the groups of carotenoids and cholesterol were correlated with CD4 count but that beta-carotene and vitamins A, C and E were not. These results are reviewed in the light of the published literature and we conclude that these abnormalities of antioxidant-micronutrients are likely to reflect a metabolic phenomenon associated with HIV infection. However, an additional contribution to these deficiencies from malabsorption later in HIV disease cannot be ruled out.

Pyomyositis has previously been described in association with human immunodeficiency virus (HIV) and as a discrete entity in HIV seronegative patients from tropical climates (tropical pyomyositis). Pyomyositis and osteomyelitis are usually considered a late complication of advanced HIV disease. We describe a patient with well-controlled HIV and both types of musculoskeletal infection. The case highlights an unusual presentation, the utility of MRI in soft tissue infection and an excellent outcome from prolonged antimicrobial therapy following surgical debridement.

There were over 600 patients on the organ waiting list in Ireland in November 2010. Ireland also witnessed a dramatic decline in the number of donors from 90 donors in 2009 to 58 donors in 2010. This case focuses on investigating the current state of organ donation in the Republic of Ireland, with the eventual goal of recommending alterations to improve the system. The need to put organ donation on a legislative framework was highlighted as well as the need for social marketing to target both the medical community and society at large to establish a moral obligation/duty to donate.