Genotype/phenotype correlations in familial hypercholesterolaemia

It is now possible to identify the specific gene defect in the majority of patients with familial hypercholesterolaemia. A potential benefit of this knowledge, in addition to helping with family screens, is to be able to predict the future clinical course. In order to do this, detailed genotype/phenotype correlation studies are required.

Familial exudative vitreoretinopathy associated with nonneovascular chronic angle-closure glaucoma

Purpose: Cases of angle-closure glaucoma in patients with familial exudative vitreoretinopathy have been reported secondary to neovascularization of the anterior segment. Cases secondary to nonneovascular mechanisms have not been previously reported. Methods: Two cases are presented of angle-closure glaucoma as a result of a nonneovascular mechanism. Results: Neovascularization was found to be a very unlikely explanation for the angle closure in these two cases. Conclusion: There may be an association between familial exudative vitreoretinopathy and angle-closure glaucoma as a direct result of a retrolental process or more likely a relative lens-iris pupillary block with a large lens.

Arbuscular mycorrhizal fungi and collembola non-additively increase soil aggregation

Soil aggregation is a principal ecosystem process mediated by soil biota. Collembola and arbuscular mycorrhizal (AM) fungi are important groups in the soil, and can interact in various ways. Few studies have examined collembola effects on soil aggregation, while many have quantified AM effects. Here, we asked if collembola have any effect on soil aggregation, and if they alter AM fungi-mediated effects on soil aggregation.

We carried out a factorial greenhouse study, manipulating the presence of both collembola and AM fungi, using two different plant species, Sorghum vulgare and Daucus carota. We measured root length and biomass, AMF (and non-AMF) soil hyphal length, root colonization, and collembolan populations, and quantified water stable soil aggregates (WSA) in four size classes.

Soil exposed to growth of AMF hyphae and collembola individually had higher WSA than control treatments. Moreover, the interaction effects between AMF and collembola were significant, with nonadditive increases in the combined application compared to the single treatments.

Our findings show that collembola can play a crucial role in maintaining ecological sustainability through promoting soil aggregation, and point to the importance of considering organism interactions in understanding formation of soil structure. (C) 2011 Elsevier Ltd. All rights reserved.

Micro-arthropod communities under human disturbance: is taxonomic aggregation a valuable tool for detecting multivariate change? Evidence from Mediterranean soil oribatid coenoses

Animal communities are sensitive to environmental disturbance, and several multivariate methods have recently been developed to detect changes in community structure. The complex taxonomy of soil invertebrates constrains the use of the community level in monitoring environmental changes, since species identification requires expertise and time. However, recent literature data on marine communities indicate that little multivariate information is lost in the taxonomic aggregation of species data to high rank taxa. In the present paper, this hypothesis was tested on two oribatid mite (oribatida, Acari) assemblages under two different kinds of disturbance: metal pollution and fires. Results indicate that data sets built at the genus and family systematic rank can detect the effects of disturbance with little loss of information. This is an encouraging result in view of the use of the community level as a preliminary tool for describing patterns of human-disturbed soil ecosystems. (c) 2006 Elsevier SAS. All rights reserved.

Familial hypocalciuric hypercalcaemia as a differential diagnosis of hyperparathyroidism:studies in a large kindred and a review of surgical experience in the condition

We have studied 46 members of a large kindred with familial hypocalciuric hypercalcaemia (FHH) after a neck exploration failed to cure hypercalcaemia in an asymptomatic patient. Serum calcium, serum phosphate, plasma parathormone and vitamin D metabolites do not distinguish affected members from patients with hyperparathyroidism. Because of the continuing debate as to whether or not FHH is a variant of, or distinct from, hyperparathyroidism, we have carried out a review of surgical experience with subtotal parathyroidectomy in hyperparathyroidism secondary to parathyroid hyperplasia and in FHH. Whereas the procedure is successful in 90 per cent of the former cases only one case of FHH has been cured by it. This provides evidence for the two conditions being aetiologically distinct. Before patients with asymptomatic hypercalcaemia are referred for parathyroid surgery the calcium:creatinine clearance ratio should be measured using a 2 h urine sample collected after an overnight fast and a fasting blood sample. If this ratio is less than 0.01 then screening of first degree relations should be undertaken before any parathyroid surgery is performed. Unnecessary surgery can therefore be avoided.

Transmission of two novel mutations in a pedigree with familial lecithin:cholesterol acyltransferase deficiency:structure-function relationships and studies in a compound heterozygous proband

Two novel mutations were identified in a compound heterozygous male with lecithin:cholesterol acyltransferase (LCAT) deficiency. Exon sequence determination of the LCAT gene of the proband revealed two novel heterozygous mutations in exons one (C110T) and six (C991T) that predict non-conservative amino acid substitutions (Thr13Met and Pro307Ser, respectively). To assess the distinct functional impact of the separate mutant alleles, studies were conducted in the proband's 3-generation pedigree. The compound heterozygous proband had negligible HDL and severely reduced apolipoprotein A-I, LCAT mass, LCAT activity, and cholesterol esterification rate (CER). The proband's mother and two sisters were heterozygous for the Pro307Ser mutation and had low HDL, markedly reduced LCAT activity and CER, and the propensity for significant reductions in LCAT protein mass. The proband's father and two daughters were heterozygous for the Thr13Met mutation and also displayed low HDL, reduced LCAT activity and CER, and more modest decrements in LCAT mass. Mean LCAT specific activity was severely impaired in the compound heterozygous proband and was reduced by 50% in individuals heterozygous for either mutation, compared to wild type family members. It is also shown that the two mutations impair both catalytic activity and expression of the circulating protein.

How to classify the Oldest Old according to Health Status: A study of 1160 subjects belonging to 552 90+ Italian sibships characterised by familial longevity recruited within the GeHA EU project

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90–106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) ‘‘healthy’’ subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called ‘‘Simple Model of Functional Status’’ (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Opportunistic spectrum aggregation for cognitive communications under collision constraints

We consider a collision-sensitive secondary system that intends to opportunistically aggregate and utilize spectrum of a primary system to achieve higher data rates. In such opportunistic spectrum access, secondary transmission can collide with primary transmission. When the secondary system aggregates more channels for data transmission, more frequent collisions may occur, limiting the performance obtained by the opportunistic spectrum aggregation. In this context, dynamic spectrum aggregation problem is formulated to maximize the ergodic channel capacity under the constraint of collision tolerable level. To solve the problem, we develop the optimal spectrum aggregation approach, deriving closed-form expressions for the collision probability in terms of primary user traffic load, secondary user transmission interval, and the random number of sub-channels aggregated. Our results show that aggregating only a subset of sub-channels will be a better choice, depending on the ratio of collision sensitivity requirement to the primary user traffic.

Ranking Spatial and Temporal Hotspots for Road Safety Interventions Using a Nonlinear Aggregation Approach

In recent years, the concept of a composite performance index, brought from economic and business statistics, has gained popularity in the field of road safety. The construction of the Composite Safety Performance Index (CSPI) involves the following key steps: the selection of the most appropriate indicators to be aggregated and the method used to aggregate them.

Over the last decade, various aggregation methods for estimating the CSPI have been suggested in the literature. However, recent studies indicates that most of these methods suffer from many deficiencies at both the theoretical and operational level; these include the correlation and compensability between indicators, as well as their high “degree of freedom” which enables one to readily manipulate them to produce desired outcomes.

The purpose of this study is to introduce an alternative aggregation method for the estimation of the CSPI, which is free from the aforementioned deficiencies. In contrast with the current aggregation methods, which generally use linear combinations of road safety indicators to estimate a CSPI, the approach advocated in this study is based on non-linear combinations of indicators and can be summarized into the following two main steps: the pairwise comparison of road safety indicators and the development of marginal and composite road safety performance functions. The introduced method has been successfully applied to identify and rank temporal and spatial hotspots for Northern Ireland, using road traffic collision data recorded in the UK STATs19 database. The obtained results highlight the promising features of the proposed approach including its stability and consistency, which enables significantly reduced deficiencies associated with the current aggregation methods. Progressively, the introduced method could evolve into an intelligent support system for road safety assessment.

Functional role of microarthropods in soil aggregation

Soil aggregation has received a lot of attention in the last years; however, the focus was mostly on soil microorganismsor larger soil fauna, especially earthworms. The impact of the large group of microarthropods, e.g. Collembola and Acari, is nearly unknown and hence underrepresented in the literature. Here we propose and discuss potential direct and indirect mechanisms of how microarthropods could influence this process with the focus on collembolans, which are in general a relatively well studied taxon.Indirect mechanisms are likely to have larger impacts on soil aggregation than direct effects. The variety of indirect mechanisms based on the provision of organic material like faecal pellets, molts and necromass as food source for microorganisms is high and given available evidence we propose that these mechanismsare the most influential. We highlight the need for overcoming the challenges of culturing and handling of these animals in order to be able to design small scale experiments and field studies which would enable us to understand the role of the different
functional groups, their interaction with other soil faunaand the impact of land use practices on soil aggregation.

Domestic fridge-freezer load aggregation to support ancillary services

Grid operators and electricity retailers in Ireland manage peak demand, power system balancing and grid congestion by offering relevant incentives to consumers to reduce or shift their load. The need for active consumers in the home using smart appliances has never been greater, due to increased variable renewable generation and grid constraints. In this paper an aggregated model of a single compressor fridge-freezer population is developed. A price control strategy is examined to quantify and value demand response savings during a representative winter and summer week for Ireland in 2020. The results show an average reduction in fridge-freezer operating cost of 8.2% during winter and significantly lower during summer in Ireland. A peak reduction of at least 68% of the average winter refrigeration load is achieved consistently during the week analysed using a staggering control mode. An analysis of the current ancillary service payments confirms that these are insufficient to ensure widespread uptake by the small consumer, and new mechanisms need to be developed to make becoming an active consumer attractive. Demand response is proposed as a new ancillary service called ramping capability, as the need for this service will increase with more renewable energy penetration on the power system.

Practical Spectrum Aggregation for Secondary Networks with Imperfect Sensing

We investigate a collision-sensitive secondary network that intends to opportunistically aggregate and utilize spectrum of a primary network to achieve higher data rates. In opportunistic spectrum access with imperfect sensing of idle primary spectrum, secondary transmission can collide with primary transmission. When the secondary network aggregates more channels in the presence of the imperfect sensing, collisions could occur more often, limiting the performance obtained by spectrum aggregation. In this context, we aim to address a fundamental query, that is, how much spectrum aggregation is worthy with imperfect sensing. For collision occurrence, we focus on two different types of collision: one is imposed by asynchronous transmission; and the other by imperfect spectrum sensing. The collision probability expression has been derived in closed-form with various secondary network parameters: primary traffic load, secondary user transmission parameters, spectrum sensing errors, and the number of aggregated sub-channels. In addition, the impact of spectrum aggregation on data rate is analysed under the constraint of collision probability. Then, we solve an optimal spectrum aggregation problem and propose the dynamic spectrum aggregation approach to increase the data rate subject to practical collision constraints. Our simulation results show clearly that the proposed approach outperforms the benchmark that passively aggregates sub-channels with lack of collision awareness.

Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma:analysis of a clinic-based population

Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history.