Genetics of Healthy Aging in Europe.The EU-Integrated Project GEHA (GEnetics of Healthy Aging)

The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing Genomics Institute from China), is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced old age in good cognitive and physical function and in the absence of major age-related diseases. To achieve this aim a coherent, tightly integrated program of research that unites demographers, geriatricians, geneticists, genetic epidemiologists, molecular biologists, bioinfomaticians, and statisticians has been set up. The working plan is to: (a) collect DNA and information on the health status from an unprecedented number of long-lived 90+ sibpairs (n = 2650) and of younger ethnically matched controls (n = 2650) from 11 European countries; (b) perform a genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals); this investigation will be followed by linkage disequilibrium mapping (LD mapping) of the candidate chromosomal regions; (c) study in cases (i.e., the 2650 probands of the sibpairs) and controls (2650 younger people), genomic regions (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in previous studies as possible candidates to harbor longevity genes; (d) genotype all recruited subjects for apoE polymorphisms; and (e) genotype all recruited subjects for inherited as well as epigenetic variability of the mitochondrial DNA (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms, within the framework of centralized databases for phenotypic, genetic, and mtDNA data. Additional advanced approaches (bioinformatics, advanced statistics, mathematical modeling, functional genomics and proteomics, molecular biology, molecular genetics) are envisaged to identify the gene variant(s) of interest. The experimental design will also allow (a) to identify gender-specific genes involved in healthy aging and longevity in women and men stratified for ethnic and geographic origin and apoE genotype; (b) to perform a longitudinal survival study to assess the impact of the identified genetic loci on 90+ people mortality; and (c) to develop mathematical and statistical models capable of combining genetic data with demographic characteristics, health status, socioeconomic factors, lifestyle habits.

A Case Study in Policy Delivery:Examining Social Inclusion through Interpretation and Practice

The current body of literature regarding social inclusion and the arts tends to focus
on two areas: the lack of clear or common understanding of the terminology involved
(GLLAM, 2000) and the difficulty in measuring impact (Newman 2001). Further, much
of the literature traces the historical evolution of social inclusion policy within the arts
from a political and social perspective (Belfiore & Bennett, 2007), whilst others
examine the situation in the context of the museum as an institution more generally
(Sandell, 2002b). Such studies are essential; however they only touch on the
importance of understanding the context of social inclusion programmes. As each
individual’s experience of exclusion (or inclusion) is argued to be different (Newman
et al., 2005) and any experience is also process-based (SEU 2001), there is a need
for more thorough examination of the processes underpinning project delivery
(Butterfoss, 2006), particularly within a field that has its own issues of exclusion, such
as the arts (Bourdieu & Darbel, 1991). This paper presents case study findings of a
programme of contemporary arts participation for adults with learning difficulties
based at an arts centre in Liverpool. By focusing on practice, the paper applies
Wenger’s (1998) social theory of learning in order to assert that rather than search
for measurable impacts, examining the delivery of programmes within their individual
contexts will provide the basis for a more reflective practice and thus more effective
policy making.

Bond quality of cross-laminated timber from Irish Sitka spruce

The potential use of Irish-grown Sitka spruce for cross-laminated timber (CLT) manufacture is investigated as this would present new opportunities and novel products for Irish timber in the home and export markets. CLT is a prefabricated multilayer engineered wood product made of at least three orthogonally bonded layers of timber. In order to increase rigidity and stability, successive layers of boards are placed cross-wise to form a solid timber panel. Load-bearing CLT wall and floor panels are easily assembled on site to form multi-storey buildings. This improves construction and project delivery time, reduces costs,
and maximises efficiency on all levels.

The paper addresses the quality of the interface bond between the laminations making up the panels, which is of fundamental importance to the load bearing capacity. Therefore, shear tests were carried out on nine test bars of three glue lines each. Moreover, delamination tests were performed on samples subjected to accelerated aging, in order to assess the durability of bonds subjected to severe environmental conditions. In addition, this paper gives an indication on thickness tolerances of planed Irish Sitka spruce lamellas, which is likely to be a critical factor for bonding quality and adhesive selection. The test results of bond quality presented in this study were within requirements of prEN 16351:2013.

Non-targeted effects of ionising radiation-Implications for low dose risk

Non-DNA targeted effects of ionising radiation, which include genomic instability, and a variety of bystander effects including abscopal effects and bystander mediated adaptive response, have raised concerns about the magnitude of low-dose radiation risk. Genomic instability, bystander effects and adaptive responses are powered by fundamental, but not clearly understood systems that maintain tissue homeostasis. Despite excellent research in this field by various groups, there are still gaps in our understandfng of the likely mechanisms associated with non-DNA targeted effects, particularly with respect to systemic (human health) consequences at low and intermediate doses of ionising radiation. Other outstanding questions include links between the different non-targeted responses and the variations. in response observed between individuals and cell lines, possibly a function of genetic background. Furthermore, it is still not known what the initial target and early interactions in cells are that give rise to non-targeted responses in neighbouring or descendant cells. This paper provides a commentary on the current state of the field as a result of the non-targeted effects of ionising radiation (NOTE) Integrated Project funded by the European Union. Here we critically examine the evidence for non-targeted effects, discuss apparently contradictory results and consider implications for low-dose radiation health effects. (C) 2012 Elsevier B.V. All rights reserved.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system

Purpose: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac.

Methods and Materials: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan.

Results: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam.

Conclusions: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac. © 2014.

Client's assessment of architects' performance in building delivery process: Evidence from Nigeria

The overall intent of this research is to provide architects with information that can be used to improve their performance so as to optimally satisfy the client's requirements and achieve high-quality overall project performance in Nigerian construction industry. Architect performance criteria were identified based on literature within the domain of architect responsibilities. The assessment of architects’ performance was carried out through a questionnaire survey of clients of recently completed building projects in Nigeria. Analysis of data includes comparison of criteria using importance–performance index analysis. Factor analysis was carried out on criteria where architects are falling below average, to group and explore the latent structure of the criteria in the data. The results showed that the architect needs to focus on management skills and ability, buildability, design quality, project communication, project integration and client focus. These results would encourage architects to perform better within their full responsibilities in the building delivery process and deliver high-quality projects within Nigerian construction industry.

Contribution of 30 Biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: The MONICA, risk, genetics, archiving and monograph (MORGAM) biomarker project

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study.
Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008).
Conclusions— The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.

An integrated multi-sensor data fusion algorithm and autopilot iImplementation in an uninhabited surface craft

Unmanned surface vehicles (USVs) are able to accomplish difficult and challenging tasks both in civilian and defence sectors without endangering human lives. Their ability to work round the clock makes them well-suited for matters that demand immediate attention. These issues include but not limited to mines countermeasures, measuring the extent of an oil spill and locating the source of a chemical discharge. A number of USV programmes have emerged in the last decade for a variety of aforementioned purposes. Springer USV is one such research project highlighted in this paper. The intention herein is to report results emanating from data acquired from experiments on the Springer vessel whilst testing its advanced navigation, guidance and control (NGC) subsystems. The algorithms developed for these systems are based on soft-computing methodologies. A novel form of data fusion navigation algorithm has been developed and integrated with a modified optimal controller. Experimental results are presented and analysed for various scenarios including single and multiple waypoints tracking and fixed and time-varying reference bearings. It is demonstrated that the proposed NGC system provides promising results despite the presence of modelling uncertainty and external disturbances.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

Pathways for delivery of surface water nutrients to receptors

Diffuse contaminants can make their way into rivers via a number of different pathways, including overland flow, interflow, and shallow and deep groundwater. Identification of the key pathway(s) delivering contaminants to a receptor is important for implementing effective water management strategies. The ‘Pathways Project’, funded by the Irish Environmental Protection Agency, is developing a catchment management tool that will enable practitioners to identify the critical source areas for diffuse contaminants, and the key pathways of interest in assessing contaminant problems on a catchment and sub-catchment scale.
One of the aims of the project is to quantify the flow and contaminant loadings being delivered to the stream via each of the main pathways. Chemical separation of stream event hydrographs is being used to supplement more traditional physical hydrograph separation methods. Distinct, stable chemical signatures are derived for each of the pathway end members, and the proportion of flow from each during a rainfall event can be determined using a simple mass balance approach.
Event sampling was carried out in a test catchment underlain by poorly permeable soils and bedrock, which is predominantly used for grazing with a number of one-off rural residential houses. Results show that artificial field drainage, which includes subterranean land drains and collector drains around the perimeters of the 1 to 10 ha fields, plays an important role in the delivery of flow and nutrients to the streams in these types of hydrogeological settings.
Nitrate infiltrates with recharge and is delivered to the stream primarily via the artificial drains and the shallow groundwater pathway. Longitudinal stream profiles show that the nitrate load input is relatively uniform over the 8 km length of the stream at high flows, suggesting widespread diffuse contaminant input. In contrast, phosphorus is adsorbed in the clay-rich soil and is transported mainly via the overland flow pathway and the artificial drains. Longitudinal stream profiles for phosphorus suggest a pattern of more discrete points of phosphorus inputs, which may be related to point sources of contamination.
These techniques have application elsewhere within a toolkit of methods for determining the key pathways delivering contaminants to surface water receptors.

Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

The stress process in palliative cancer care:A qualitative study on informal caregiving and its implication for the delivery of care

Objective: The primary objective of this study was to examine how the comprehensive nature of the Stress Process Model could elucidate on the stressors associated with caring for a palliative cancer patient. Method: A qualitative research strategy involving home-based face-to-face interviews with 12 bereaved family caregivers was used to examine the caregiving experience. Results: The primary stressors associated with caring for the palliative cancer care patients stemmed from care recipient symptoms and personal care needs. The absence of adequate support from the formal health care delivery system was a consistent message from all participants. There was evidence of financial stress primarily associated with the purchase of private home care to supplement formal care. In contrast, the resources that family caregivers relied on to moderate the stressful effects of caregiving included extended family, friends, and neighbors. While the stress of direct caregiving was high, the study revealed that formal care was also a significant source of stress for family caregivers. Conclusion: It was concluded that an appropriately financed, integrated system of care that followed a person-centered philosophy of care would best meet the needs of the patient and his or her family. © The Author(s) 2010.