Meta-analysis of 32 genome-wide linkage studies of schizophrenia

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P-SR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. Molecular Psychiatry (2009) 14, 774-785; doi:10.1038/mp.2008.135; published online 30 December 2008

Plasma cell polyp of the vocal fold

Plasma cell polyps of the vocal fold (plasma cell granulomas) are rare inflammatory polyps of the larynx. They should be included in the clinical and histological differential diagnosis of laryngeal polyps. Histologically they are polyclonal aggregates of plasma cells. It is essential to distinguish them from monoclonal, neoplastic plasma cell proliferations. The treatment of choice is surgical resection, although radiotherapy, laser ablation, antibiotics and steroids have been used successfully. We present a case of plasma cell granuloma presenting as a vocal fold polyp, treated surgically.

The use of process simulation methods in support of organisational learning in availability contracting

Traditional business models in the aerospace industry are based on a conventional supplier to customer relationship based on the design, manufacture and subsequent delivery of the physical product. Service provision, from the manufacturer's perspective, is typically limited to the supply of procedural documentation and the provision of spare parts to the end user as the product passes through the latter stages of its intended lifecycle. Challenging economic and political conditions have resulted in end users re-structuring their core business activities, particularly in the defence sector. This has resulted in the need for original equipment manufacturers (OEMs) to integrate and manage support service activities in partnership with the customer to deliver platform availability. This improves the probability of commercial sustainability for the OEM through shared operational risks while reducing the cost of platform ownership for the customer. The need for OEMs to evolve their design, manufacture and supply strategies by focusing on customer requirements has revealed a need for reconstruction of traditional internal behaviours and design methodologies. Application of organisational learning is now a well recognised principle for innovative companies to achieve long term growth and sustained technical development, and hence, greater market command. It focuses on the process by which the organisation's knowledge and value base changes, leading to improved problem solving ability and capacity for action. From the perspective of availability contracting, knowledge and the processes by which it is generated, used and retained, become primary assets within the learning organisation. This paper will introduce the application of digital methods to asset management by demonstrating how the process of learning can benefit from a digital approach, how product and process design can be integrated within a virtual framework and finally how the approach can be applied in a service context.

Evaluation of cement stresses in finite element analyses of cemented orthopaedic implants

Stress analysis of the cement fixation of orthopaedic implants to bone is frequently? carried out using finite element analysis. However, the stress distribution in the cement laver is usually intricate, and it is difficult to report it in a way that facilitates comparison of implants for pre-clinical testing. To study this problem, and make recommendations for stress reporting, a finite element analysis of a hip prosthesis implanted into a synthetic composite femur is developed. Three cases are analyzed: a fully bonded implant, a debonded implant, and a debonded implant where the cement is removed distal to the stein tip. In addition to peak stresses, and contour and vector plots, a stressed volume and probability-of-failure analysis is reported. It is predicted that the peak stress is highest for the debonded stem, and that removal of the distal cement more than halves this peak stress. This would suggest that omission of the distal cement is good for polished prostheses (as practiced for the Exeter design). However; if the percentage of cement stressed above a certain threshold (say 3 MPa) is considered, then the removal of distal cement is shown to be disadvantageous because a higher volume of cement is stressed to above the threshold. Vector plots clearly demonstrate the different load transfer for bonded and debonded prostheses: A bonded stein generates maximum tensile stresses in the longitudinal direction, whereas a debonded stem generates most tensile stresses in the hoop direction, except near the tip where tensile longitudinal stresses occur due to subsidence of the stein. Removal of the cement distal to the tip allows greater subsidence but alleviates these large stresses at the tip, albeit at the expense of increased hoop stresses throughout the mantle. It is concluded that a thorough analysis of cemented implants should not report peak stress, which can be misleading, but rather stressed volume, and that vector plots should be reported if a precise analysis of the load transfer mechanism is required.

Distribution of the Demmel Condition Number of Wishart Matrices

This paper studies the Demmel condition number of Wishart matrices, a quantity which has numerous applications to wireless communications, such as adaptive switching between beamforming and diversity coding, link adaptation, and spectrum sensing. For complex Wishart matrices, we give an exact analytical expression for the probability density function (p.d.f.) of the Demmel condition number, and also derive simplified expressions for the high tail regime. These results indicate that the condition of complex Wishart matrices is dominantly decided by the difference between the matrix dimension and degree of freedom (DoF), i.e., the probability of drawing a highly ill conditioned matrix decreases considerably when the difference between the matrix dimension and DoF increases. We further investigate real Wishart matrices, and derive new expressions for the p.d.f. of the smallest eigenvalue, when the difference between the matrix dimension and DoF is odd. Based on these results, we succeed to obtain an exact p.d.f. expression for the Demmel condition number, and simplified expressions for the high tail regime.

On the Performance of Eigenvalue-Based Cooperative Spectrum Sensing for Cognitive Radio

In this paper, the distribution of the ratio of extreme eigenvalues of a complex Wishart matrix is studied in order to calculate the exact decision threshold as a function of the desired probability of false alarm for the maximum-minimum eigenvalue (MME) detector. In contrast to the asymptotic analysis reported in the literature, we consider a finite number of cooperative receivers and a finite number of samples and derive the exact decision threshold for the probability of false alarm. The proposed exact formulation is further reduced to the case of two receiver-based cooperative spectrum sensing. In addition, an approximate closed-form formula of the exact threshold is derived in terms of a desired probability of false alarm for a special case having equal number of receive antennas and signal samples. Finally, the derived analytical exact decision thresholds are verified with Monte-Carlo simulations. We show that the probability of detection performance using the proposed exact decision thresholds achieves significant performance gains compared to the performance of the asymptotic decision threshold.

Time-resolved optical spectroscopy of the pulsating DA white dwarf HS0507+0434B - New constraints on mode identification and pulsation properties

We present a detailed analysis of time-resolved optical spectra of the ZZ Ceti white dwarf, HS 0507+0434B. Using the wavelength dependence of observed mode amplitudes, we deduce the spherical degree, l, of the modes, most of which have l = 1. The presence of a large number of combination frequencies (linear sums or differences of the real modes) enabled us not only to test theoretical predictions but also to indirectly infer spherical and azimuthal degrees of real modes that had no observed splittings. In addition to the above, we measure line-of-sight velocities from our spectra. We find only marginal evidence for periodic modulation associated with the pulsation modes: at the frequency of the strongest mode in the lightcurve, we measure an amplitude of 2.6 +/- 1.0 kms(-1), which has a probability of 2% of being due to chance; for the other modes, we find lower values. Our velocity amplitudes and upper limits are smaller by a factor of two compared to the amplitudes found in ZZ Psc. We find that this is consistent with expectations based on the position of HS 0507+0434B in the instability strip. Combining all the available information from data such as ours is a first step towards constraining atmospheric properties in a convectionally unstable environment from an observational perspective.

Monitoring and population estimation of the European badger (Meles meles) in Northern Ireland

The estimation of animal abundance has a central role in wildlife management and research, including the role of badgers Meles meles in bovine tuberculosis transmission to cattle. This is the first study to examine temporal change in the badger population of Northern Ireland over amedium- to long-term time frame of 14-18 years by repeating a national survey first conducted during 1990-1993. A total of 212 1-km2 squares were surveyed during 2007-2008 and the number, type and activity of setts therein recorded. Badgers were widespread with 75% of squares containing at least one sett. The mean density of activemain setts,which was equivalent to badger social group density, was 0.56 (95%CI: 0.46-0.67) active main setts per km2 during 2007-2008. Social group density varied significantly among landclass groups and counties. The total number of social groups was estimated at 7,600 (95%CI: 6,200-9,000) and, not withstanding probable sources of error in estimating social group size, the total abundance of badgers was estimated to be 34,100 (95% CI: 26,200-42,000). There was no significant change in the badger population from that recorded during 1990-1993. A resource selection model provided a relative probability of sett construction at a spatial scale of 25m. Sett locations were negatively associated with elevation and positively associated with slope, aspect, soil sand content, the presence of cover, and the area of improved grassland and arable agriculture within 300 m.

Complex fiber bundle model for optimization of heterogeneous materials

We propose a complex fiber bundle model for the optimization of heterogeneous materials, which consists of many simple bundles. We also present an exact and compact recursion relation for the failure probability of a simple fiber bundle model with local load sharing, which is more efficient than the ones reported previously. Using a ''renormalization method'' and the recursion relation developed for the simple bundle, we calculate the failure probabilities of the complex fiber bundle. When the total number of fibers is given, we find that there exists an optimum way to organize the complex bundle, in which one gets a stronger bundle than in other ways.

Why is housing tenure associated with a lower risk of admission to a nursing or residential home? Wealth, health and the incentive to keep 'my home'

Background Previous research has shown that home ownership is associated with a reduced risk of admission to institutional care. The extent to which this reflects associations between wealth and health, between wealth and ability to buy in care or increased motivation to avoid admission related to policies on charging is unclear. Taking account of the value of the home, as well as housing tenure, may provide some clarification as to the relative importance of these factors.
Aims To analyse the probability of admission to residential and nursing home care according to housing tenure and house value.
Methods Cox regression was used to examine the association between home ownership, house value and risk of care home admissions over 6 years of follow-up among a cohort of 51 619 people aged 65 years or older drawn from the Northern Ireland Longitudinal Study, a representative sample of approximate to 28% of the population of Northern Ireland.
Results 4% of the cohort (2138) was admitted during follow-up. Homeowners were less likely than those who rented to be admitted to care homes (HR 0.77, 95% CI 0.70 to 0.85, after adjusting for age, sex, health, living arrangement and urban/rural differences). There was a strong association between house value/tenure and health with those in the highest valued houses having the lowest odds of less than good health or limiting long-term illness. However, there was no difference in probability of admission according to house value; HRs of 0.78 (95% CI 0.67 to 0.90) and 0.81 (95% CI 0.70 to 0.95), respectively, for the lowest and highest value houses compared with renters.
Conclusions The requirement for people in the UK with capital resources to contribute to their care is a significant disincentive to institutional admission. This may place an additional burden on carers.

Platinum and Palladium in Semiconductor Photocatalytic Systems FACTORS AFFECTING THE PURIFICATION OF WATER AND AIR

A wide range of organic pollutants can be destroyed by semiconductor photocatalysis using titania. The purification of water and air contaminated with organic pollutants has been investigated by semiconductor photocatalysis for many years and in attempts to improve the purification rate platinum and palladium have been deposited, usually as fine particles, on the titania surface. Such deposits are expected to improve the rate of reduction of oxygen and so reduce the probability of electron-hole recombination and increase the overall rate of the reaction. The effectiveness of the deposits is reviewed here and appears very variable with reported rate enhancement factors ranging from 8 to 0.1. Semiconductor photocatalysis can be used to purify air (at temperatures > 100 degrees C) and Pt deposits can markedly improve the overall rate of mineralisation. However, volatile organic compounds containing an heteroatom can deactivate the photocatalyst completely and irreversibly. Factors contributing to the success of the processes are considered. The use of chloro-Pt(IV)-titania and other chloro-platinum group metals-titania complexes as possible visible light sensitisers for water and air purification is briefly reviewed.

Behavioural and cognitive behavioural training interventions for assisting foster carers in the management of difficult behaviour.

Background The provision of training for foster carers is now seen as an important factor contributing to the successful outcome of foster care placements. Since the late 1960s, foster carer training programs have proliferated, and few of the many published and unpublished training curricula have been systematically evaluated. The advent of cognitive-behavioural therapy (CBT) and the research evidence demonstrating its effectiveness as a psychotherapeutic treatment of choice for a range of emotional and behavioural problems, has prompted the development of CBT-based training programmes. CBT approaches to foster care training derive from a ’skill-based’ training format that also seeks to identify and correct problematic thinking patterns that are associated with dysfunctional behaviour by changing and/or challenging maladaptive thoughts and beliefs. Objectives To assess the effectiveness of cognitive-behavioural training interventions in improving a) looked-after children’s behavioural/relationship problems, b) foster carers’ psychological well-being and functioning, c) foster family functioning, d) foster agency outcomes. Search methods We searched databases including: CENTRAL (Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to September 2006), EMBASE (January 1980 to September 2006), CINAHL (January 1982 to September 2006), PsycINFO (January 1872 to September 2006), ASSIA (January 1987 to September 2006), LILACS (up to September 2006), ERIC (January 1965 to September 2006), Sociological Abstracts (January 1963 to September 2006), and the National Research Register 2006 (Issue 3).We contacted experts in the field concerning current research. Selection criteria Random or quasi randomised studies comparing behavioural or cognitive-behavioural-base Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main results Six trials involving 463 foster carers were included. Behavioural and cognitive-behavioural training interventions evaluated to date appear to have very little effect on outcomes relating to looked-after children, assessed in relation to psychological functioning, extent of behavioural problems and interpersonal functioning. Results relating to foster carer(s) outcomes also show no evidence of effectiveness in measures of behavioural management skills, attitudes and psychological functioning. Analysis pertaining to fostering agency outcomes did not show any significant results. However, caution is needed in interpreting these findings as their confidence intervals are wide. Authors’ conclusions There is currently little evidence about the efficacy of behavioural or cognitive-behavioural training intervention for foster carers. The need for further research in this area is highlighted.

Post-mortem examination of a wild muntjac from Northern Ireland.

1. Deer are of major concern with regards to impacts on biodiversity, forestry and agriculture as well as human health. The invasive Reeves’ muntjac deer Muntiacus reevesi, native to Asia but established in Great Britain, has recently appeared in the wild in Ireland.

2. The first verified record in the wild in Northern Ireland was confirmed during June 2009 as a result of a road traffic accident near Newtownards, Co. Down. The second record was a culled animal shot in the grounds of Mount Stewart, Co. Down during June 2011.

3. The current report aimed to perform a detailed investigation of the most recently obtained animal to establish a) its age, b) its genetic relationship with the first animal and c) the threat it might pose in terms of carrying endo- or ecto-parasites or other micro-pathogens, principally viruses and bacteria.

4. Analysis of its dentition suggested the culled animal was 56 weeks old (range 55-57 weeks).

5. Genetic analysis indicated that there was no possibility of a father-son relationship with the buck killed in 2009. There was a 6.25% probability of both individuals being full-sibs and a 25% probability of a half-sib relationship.

6. The deer was free from all the major pathogens. Most significantly, a novel species of Gammaherpesvirus was detected most closely matching type 2 ruminant rhadinovirus (Gammaherpesvirinae) from mule deer. Further sequencing is required to provide a definitive classification. There is no evidence suggesting this virus is pathogenic but its detection is nonetheless of concern.

7. During late 2009 (after the first animal was recovered) and early 2010, there were a number of sightings of muntjac within the vicinity of Mount Stewart. Our results indicate that the animal shot in June 2011 could not have been this same animal, as the shot animal must have been born in spring 2010. Moreover, genetic analysis indicates that the two recovered individuals were highly unlikely to share the same mother and father, suggesting they were the offspring of a minimum of three breeding adults (two fathers and one mother or two mothers and one father). This brings the total number of known individuals to 5 including the two offspring. The location of the breeding adults is unknown and may be either in captivity with subsequent escapees, or deliberate releases, or be free living in the wild. However, a further sighting during early 2012 may suggest a wild origin.

An investigation of clustered radiation-induced lesions in DNA

Recent track structure modelling studies indicate that radiation induced damage to DNA consists of a spectrum of different lesions of varying complexity. There is considerable evidence to suggest that, in repair-proficient systems, it is only the small proportion of more complex forms that is responsible for most of the biological effect. The complex lesions induced consist initially of clustered radical sites and a knowledge of their special chemistry is important in modelling how they react to form the more stable products that are processed by the repair systems. However, much of the current understanding of the chemical stage of radiation has developed from single-radical systems and there is a need to translate this to the more complex reactions that are likely to occur at the important multiple radical sites. With low LET radiation, DNA dsb may derive either from single-radical attack that damages both strands by a transfer mechanism, or from pairs of radical sites induced in close proximity, with one or more radical on each strand. With high LET radiation, modelling studies indicate that there is an increased probability of dsb arising from sites with more than two radical centres, leading to a greater frequency of more complex types of break. The spectrum of these lesions depends on the overall outcome of consecutive physical and chemical processes. The initial pattern of radical damage is determined by the energy depositions on and around the DNA, according to the type of radiation. This pattern is then modified by scavengers that inhibit the formation of radicals on the DNA, and by agents that either chemically repair (e.g. thiols) or fix (e.g. oxygen) a large fraction of these radicals. The reaction kinetics associated with clustered radical sites will differ from those of single sites: (1) because of the opportunities for interactions between the radicals themselves; and (2) because certain endpoints, e.g. a dsb, may require a combination of the products of two or more radicals. Fast response techniques using pulsed low and high LET irradiation have been established to measure the reactions of radical sites on pBR322 plasmid DNA with oxygen and thiols with a view to obtaining information about cluster size. This paper describes experimental approaches to explore the role of the chemical stage of the radiation effect in relation to lesion complexity.

A comparison of the chemical repair rates of free radical precursors of DNA damage and cell killing in Chinese hamster V79 cells.

One of the important temporal stages of radiation action in cellular systems is the chemical phase, where oxygen fixation reactions compete with chemical repair reactions involving reducing agents such as GSH. Using the gas explosion technique it is possible to follow the kinetics of these fast (> 1 ms) reactions in intact cells. We have compared the chemical repair kinetics of the oxygen-dependent free radical precursors leading to DNA single-strand and double-strand breaks, measured using filter elution techniques, with those leading to cell killing in V79 cells. The chemical repair rates for DNA dsb (670s-1 at pH 7.2 and 380s-1 at pH 9.6) and cell killing (530s-1) were similar. This is in agreement with the important role of DNA dsb in radiation induced cell lethality. The rate for DNA ssb precursors was significantly slower (210s-1). The difference in rate between DNA ssb and dsb precursors may be explained on the basis of a dsb free radical precursor consisting of a paired radical, one radical on each strand. The instantaneous probability of one or other of these radicals being chemically repaired and not proceeding to form a dsb will be twice that of a ssb radical precursor. This agrees well with the concept of locally multiply damaged sites (LMDS) produced from clusters of ionizations in DNA (Ward 1985).