Genome-wide linkage analysis for human longevity: Genetics of healthy aging study

Clear evidence exists for heritability of humanlongevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project. In the joint linkage analyses, we observed four regions that show linkage with longevity; chromosome 14q11.2 (LOD = 3.47), chromosome 17q12-q22 (LOD = 2.95), chromosome 19p13.3-p13.11 (LOD = 3.76), and chromosome 19q13.11-q13.32 (LOD = 3.57). To fine map these regions linked to longevity, we performed association analysis using GWAS data in a subgroup of 1228 unrelated nonagenarian and 1907 geographically matched controls. Using a fixed-effect meta-analysis approach, rs4420638 at the TOMM40/ APOE/APOC1 gene locus showed significant association with longevity (P-value = 9.6 × 10). By combined modeling of linkage and association, we showed that association of longevity with APOEe4 and APOEe2 alleles explain the linkage at 19q13.11-q13.32 with P-value = 0.02 and P-value = 1.0 × 10, respectively. In the largest linkage scan thus far performed for human familial longevity, we confirm that the APOE locus is a longevity gene and that additional longevity loci may be identified at 14q11.2, 17q12-q22, and 19p13.3-p13.11. As the latter linkage results are not explained by common variants, we suggest that rare variants play an important role in human familial longevity.

The geometry of unstented and stented pig common carotid artery bypass grafts

The long-term success of arterial bypass grafting with autologous saphenous veins is limited by neointimal hyperplasia (NIH), which seemingly develops preferentially at sites where hydrodynamic wall shear is low. Placement of a loose-fitting, porous stent around end-to-end, or end-to-side, autologous saphenous vein grafts on the porcine common carotid artery has been found significantly to reduce NIH, but the mechanism is unclear. In a preliminary study, we implanted autologous saphenous vein grafts bilaterally on the common carotid arteries of pigs, placing a stent around one graft and leaving the contralateral graft unstented. At sacrifice 1 month post implantation, the grafts were pressure fixed in situ and resin casts were made. Unstented graft geometry was highly irregular, with non-uniform dilatation, substantial axial lengthening, curvature, kinking, and possible long-pitch helical distortion. In contrast, stented grafts showed no major dilatation, lengthening or curvature, but there was commonly fine corrugation, occasional slight kinking or narrowing of segments, and possible long-pitch helical distortion. Axial growth of grafts against effectively tethered anastomoses could account for these changes. CFD studies are planned, using 3D MR reconstructions, on the effects of graft geometry on the flow. Abnormality of the flow could favour the development of vascular pathology, including NIH.

Clarification of rubber mill wastewater by a plant based biopolymer- comparison with common inorganic coagulants

Background: In this study, the efficiency of Guar gum as a biopolymer has been compared with two other widely used inorganic coagulants, ferric chloride (FeCl3) and aluminum chloride (AlCl3), for the treatment of effluent collected from the rubber-washing tanks of a rubber concentrate factory. Settling velocity distribution curves were plotted to demonstrate the flocculating effect of FeCl3, AlCl3 and Guar gum. FeCl3 and AlCl3 displayed better turbidity removal than Guar gum at all settling velocities.

Result: FeCl3, AlCl3 and Guar gum removed 92.8%, 88.2% and 88.1% turbidity, respectively, of raw wastewater at a settling velocity of 0.1 cm min-1, respectively. Scanning electron microscopic (SEM) study conducted on the flocs revealed that Guar gum and FeCl3produced strong intercoiled honeycomb patterned floc structure capable of entrapping suspended particulate matter. Statistical experimental design Response Surface Methodology (RSM) was used to design all experiments, where the type and dosage of flocculant, pH and mixing speed were taken as control factors and, an optimum operational setting was proposed.

Conclusion: Due to biodegradability issues, the use of Guar gum as a flocculating agent for wastewater treatment in industry is highly recommended.

A review of spatial and temporal variation in grey and common seal diet in the United Kingdom and Ireland

Knowledge about the diet of fish-eating predators is critical when evaluating conflicts with the fishing industry. Numerous primary studies have examined the diet of grey seals Halichoerus grypus and common seals Phoca vitulina in a bid to understand the ecology of these predators. However, studies of large-scale spatial and temporal variation in seal diet are limited. Therefore this review combines the results of seal diet studies published between 1980 and 2000 to examine how seal diet varies at a range of spatial and temporal scales. Our results revealed extensive spatial variation in gadiform, perciform and flatfish consumption, likely reflecting variation in prey availability. Flatfish and gadiform consumption varied between years, reflecting changes in fish assemblages as a consequence of factors such as varying fishing pressures, climate change and natural fluctuations in populations. Perciform and gadiform consumption varied seasonally: in addition there was a significant interaction between season and seal species, indicating that grey and common seals exhibited different patterns of seasonal variation in their consumption of Perciformes and Gadiformes. Multivariate analysis of grey seal diet revealed spatial variation at a much smaller scale, with different species dominating the diet in different areas. The existence of spatial and temporal variation in seal diet emphasizes that future assessments of the impact of seal populations should not be based on past or localized estimates of diet and highlights the need for up-to-date, site specific estimates of diet composition in the context of understanding and resolving seal/fisheries conflict. © 2012 Marine Biological Association of the United Kingdom.

Welfare risk assessment:The benefits and common pitfalls

Risk is defined as a situation involving exposure to danger. Risk assessment by nature characterises the probability of a negative event occurring and quantifies the consequences of such an event. Risk assessment is increasingly being used in the field of animal welfare as a means of drawing comparisons between multiple welfare problems within and between species and identifying those that should be prioritised by policy-makers, either because they affect a large proportion of the population or because they have particularly severe consequences for those affected. The assessment of risk is typically based on three fundamental factors: intensity of consequences, duration affected by consequences and prevalence. However, it has been recognised that these factors alone do not give a complete picture of a hazard and its associated consequences. Rather, to get a complete picture, it is important to also consider information about the hazard itself: probability of exposure to the hazard and duration of exposure to the hazard. The method has been applied to a variety of farmed species (eg poultry, dairy cows, farmed fish), investigating housing, husbandry and slaughter procedures, as well as companion animals, where it has been used to compare inherited defects in pedigree dogs and horses. To what extent can we trust current risk assessment methods to get the priorities straight? How should we interpret the results produced by such assessments? Here, the potential difficulties and pitfalls of the welfare risk assessment method will be discussed: (i) the assumption that welfare hazards are independent; (ii) the problem of quantifying the model parameters; and (iii) assessing and incorporating variability and uncertainty into welfare risk assessments. © 2012 Universities Federation for Animal Welfare.

Exchange potential from the common energy denominator approximation for the Kohn-Sham Green's function: Application to (hyper)polarizabilities of molecular chains

An approximate Kohn-Sham (KS) exchange potential v(xsigma)(CEDA) is developed, based on the common energy denominator approximation (CEDA) for the static orbital Green's function, which preserves the essential structure of the density response function. v(xsigma)(CEDA) is an explicit functional of the occupied KS orbitals, which has the Slater v(Ssigma) and response v(respsigma)(CEDA) potentials as its components. The latter exhibits the characteristic step structure with "diagonal" contributions from the orbital densities \psi(isigma)\(2), as well as "off-diagonal" ones from the occupied-occupied orbital products psi(isigma)psi(j(not equal1)sigma). Comparison of the results of atomic and molecular ground-state CEDA calculations with those of the Krieger-Li-Iafrate (KLI), exact exchange (EXX), and Hartree-Fock (HF) methods show, that both KLI and CEDA potentials can be considered as very good analytical "closure approximations" to the exact KS exchange potential. The total CEDA and KLI energies nearly coincide with the EXX ones and the corresponding orbital energies epsilon(isigma) are rather close to each other for the light atoms and small molecules considered. The CEDA, KLI, EXX-epsilon(isigma) values provide the qualitatively correct order of ionizations and they give an estimate of VIPs comparable to that of the HF Koopmans' theorem. However, the additional off-diagonal orbital structure of v(xsigma)(CEDA) appears to be essential for the calculated response properties of molecular chains. KLI already considerably improves the calculated (hyper)polarizabilities of the prototype hydrogen chains H-n over local density approximation (LDA) and standard generalized gradient approximations (GGAs), while the CEDA results are definitely an improvement over the KLI ones. The reasons of this success are the specific orbital structures of the CEDA and KLI response potentials, which produce in an external field an ultranonlocal field-counteracting exchange potential. (C) 2002 American Institute of Physics.

Negative Silence: The unspoken future of Northern Ireland

The premise for finding common ground between unionism and nationalism in Northern Ireland in the 1998 Agreement centred on an accepted compromise regarding what the future of the province might be: continued union within the UK was assured but could be changed if unity with the Republic of Ireland was the will of the majority. In this way, Northern Ireland was suspended as if on a see-saw between the ‘two traditions’. As a consequence, the very success of power-sharing has made it difficult for parties to articulate a shared vision of Northern Ireland’s future. This paper identifies a ‘negative silence’ regarding the outlook for Northern Ireland and seeks to uncover some of its implications by analysing three of its constitutive elements. First, how the aspirational discourse of the four largest political parties has remained largely entrenched in oppositional gullies. Second, how the debate around the Shared Future framework and Cohesion, Sharing and Integration programme ironically embodies deep differences in political visions of a ‘shared’ future for Northern Ireland. Finally, interview-based reflections on how an inability to articulate a future for Northern Ireland affects the young ‘Agreement generation’ and their (dis)empowerment as citizens. The paper concludes that the thicker the fog of silence grows over the subject of Northern Ireland’s future, the bleaker this future is likely to be

Defective B cell response to TLR9 ligand (CpG-ODN), Streptococcus pneumoniae and Haemophilus influenzae extracts in common variable immunodeficiency patients

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinaemia and antibody deficiency to both T dependent and independent antigens. Patients suffer from recurrent sinopulmonary infections mostly caused by Streptococcus pneumoniae and Haemophilus influenzae, but also gastrointestinal or autoimmune symptoms. Their response to vaccination is poor or absent. In this study we investigated B cell activation induced by the TLR9 specific ligand (CpG-ODN) and bacterial extracts from S. pneumoniae and H. influenzae known to stimulate several TLR. We found that B cells from CVID patients express lower levels of CD86 after stimulation with CpG-ODN, S. pneumoniae and H. influenzae extracts in combination with anti-IgM antibody and also display a lower proliferative index when stimulated with bacterial extracts. Our results point to a broad TLR signalling defect in B lymphocytes from CVID patients that may be related to the hypogammaglobulinaemia and poor response to vaccination characteristic of these patients.

Reaching common ground:A patient-family-based conceptual framework of quality EOL care

Improvement in the quality of end-of-life (EOL) care is a priority health care issue since serious deficiencies in quality of care have been reported across care settings. Increasing pressure is now focused on Canadian health care organizations to be accountable for the quality of palliative and EOL care delivered. Numerous domains of quality EOL care upon which to create accountability frameworks are now published, with some derived from the patient/family perspective. There is a need to reach common ground on the domains of quality EOL care valued by patients and families in order to develop consistent performance measures and set priorities for health care improvement. This paper describes a meta-synthesis study to develop a common conceptual framework of quality EOL care integrating attributes of quality valued by patients and their families. © 2005 Centre for Bioethics, IRCM.

Common-sense knowledge for a computer vision system for human action recognition

This work presents a novel approach for human action recognition based on the combination of computer vision techniques and common-sense knowledge and reasoning capabilities. The emphasis of this work is on how common sense has to be leveraged to a vision-based human action recognition so that nonsensical errors can be amended at the understanding stage. The proposed framework is to be deployed in a realistic environment in which humans behave rationally, that is, motivated by an aim or a reason. © 2012 Springer-Verlag.

Common-sense reasoning for human action recognition

This paper presents a novel method that leverages reasoning capabilities in a computer vision system dedicated to human action recognition. The proposed methodology is decomposed into two stages. First, a machine learning based algorithm - known as bag of words - gives a first estimate of action classification from video sequences, by performing an image feature analysis. Those results are afterward passed to a common-sense reasoning system, which analyses, selects and corrects the initial estimation yielded by the machine learning algorithm. This second stage resorts to the knowledge implicit in the rationality that motivates human behaviour. Experiments are performed in realistic conditions, where poor recognition rates by the machine learning techniques are significantly improved by the second stage in which common-sense knowledge and reasoning capabilities have been leveraged. This demonstrates the value of integrating common-sense capabilities into a computer vision pipeline. © 2012 Elsevier B.V. All rights reserved.

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk.

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.

Collective Participation Impacts Social Identity::A Longitudinal Study with Control Data

How does participation in collective activity affect our social identifications and behavior? We investigate this question in a longitudinal questionnaire study conducted at one of the world’s largest collective events – the Magh Mela (a month-long Hindu religious festival in north India). Data gathered from pilgrims and comparable others who did not attend the event show that one month after this mass gathering was over, those who had participated (but not controls) exhibited a heightened social identification as Hindu and increased levels of religious activity (e.g., performing prayer rituals). Additional data gathered from the pilgrim respondents during the festival show that the pilgrims’ perceptions of sharing a common identity with other pilgrims, and of being able to enact their social identity in this event, predicted these outcomes.

Assessing Historical and Current Threats to Common Frog (Rana Temporaria) Populations in Ireland

Ponds are an ephemeral feature of the landscape but their large-scale loss can have profound implications for biodiversity and the persistence of amphibian populations. We quantified rates of pond loss throughout Ireland over a period of approximately 125 yr. Environmental parameters and perceived risk factors associated with the current occurrence and density of the Common Frog, Rana temporaria, were also analyzed. The numbers of farmland ponds declined by 54% between 1887–1913 and 2005–11, with most ponds and the greatest losses
in the East, coincident with agricultural intensification and human habitation. The decline of pond numbers was significant but, at approximately 0.5% per annum, was substantially less than losses recorded in other European countries. Losses were coincident with major changes to the agricultural landscape including extensive land drainage. However, losses of pond and natural wetland habitats throughout Ireland may have been partially or wholly mitigated by a synchronous expansion of artificial field margin ditches associated with drainage projects during the mid-20th Century. The ecology of the Common Frog in Ireland was similar to its ecology elsewhere and it appears largely unaffected by pollution and disturbance. Consequently, the conservation status of the frog in Ireland was judged ‘‘favorable’’ and should remain so for the foreseeable future.