Range expansion in an invasive small mammal: influence of life-history and habitat quality.

Invasive species pose a major threat to biodiversity but provide an opportunity to describe the processes that lead to changes in a species’ range. The bank vole (Myodes glareolus) is an invasive rodent that was introduced to Ireland in the early twentieth century. Given its continuing range expansion, the substantial empirical data on its spread thus far, and the absence of any eradication program, the bank vole in Ireland represents a unique model system for studying the mechanisms influencing the rate of range expansion in invasive small mammals. We described the invasion using a reaction–diffusion model informed by empirical data on life history traits and demographic parameters. We subsequently modelled the processes involved in its range expansion using a rule-based spatially explicit simulation. Habitat suitability interacted with density-dependent parameters to influence dispersal, most notably the density at which local populations started to donate emigrating individuals, the number of dispersing individuals and the direction of dispersal. Whilst local habitat variability influenced the rate of spread, on a larger scale the invasion resembled a simple reaction–diffusion process. Our results suggest a Type 1 range expansion where the rate of expansion is generally constant over time, but with some evidence for a lag period following introduction. We demonstrate that a two-parameter empirical model and a rule-based spatially explicit simulation are sufficient to accurately describe the invasion history of a species that exhibits a complex, density-dependent pattern of dispersal.

Genome-Wide Association Study of Multiplex Schizophrenia Pedigrees

OBJECTIVE The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs). METHOD The family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs. RESULTS No genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10-17, explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene [NRXN1]) was similar to previous case-control studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families. CONCLUSIONS Many common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researchers should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied.

Mean shift based gradient vector flow for image segmentation

In recent years, gradient vector flow (GVF) based algorithms have been successfully used to segment a variety of 2-D and 3-D imagery. However, due to the compromise of internal and external energy forces within the resulting partial differential equations, these methods may lead to biased segmentation results. In this paper, we propose MSGVF, a mean shift based GVF segmentation algorithm that can successfully locate the correct borders. MSGVF is developed so that when the contour reaches equilibrium, the various forces resulting from the different energy terms are balanced. In addition, the smoothness constraint of image pixels is kept so that over- or under-segmentation can be reduced. Experimental results on publicly accessible datasets of dermoscopic and optic disc images demonstrate that the proposed method effectively detects the borders of the objects of interest.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II:Schizophrenia

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10,337 cases and 11,174 controls (OR=1.10; p-value=3.79×10(-5)). Thus, it appears that rare and common variants in a single gene - FBN2 - can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.

Biomarkers in nutrition: new frontiers in research and application

Nutritional biomarkers-biochemical, functional, or clinical indices of nutrient intake, status, or functional effects--are needed to support evidence-based clinical guidance and effective health programs and policies related to food, nutrition, and health. Such indices can reveal information about biological or physiological responses to dietary behavior or pathogenic processes, and can be used to monitor responses to therapeutic interventions and to provide information on interindividual differences in response to diet and nutrition. Many nutritional biomarkers are available; yet there has been no formal mechanism to establish consensus regarding the optimal biomarkers for particular nutrients and applications.

Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.

Impact of tooth replacement on the nutritional status of partially dentate elders

OBJECTIVES: The aim of this study was to compare the impact of two different tooth replacement strategies on the nutritional status of partially dentate older patients. Nutritional status was measured using the full version of the Mini Nutritional Assessment (MNA) and the short form of the Mini Nutritional Assessment (MNA-SF).

MATERIALS AND METHODS: A randomised controlled clinical trial was conducted (Trial Registration no. ISRCTN26302774). Partially dentate patients aged 65 years and older were recruited and randomly allocated to the two different treatment groups: the removable partial dentures (RPD) group and the shortened dental arch (SDA) group. Nutritional status was measured using the MNA and MNA-SF administered at baseline and 1, 6 and 12 months after treatment intervention by a research nurse blinded to the treatment group allocation of all participants.

RESULTS: Data collected using the full version of the MNA showed significant improvements in mean MNA scores over the length of the study (p < 0.05). For the entire patient group, there was a mean increase of 0.15 points at 6 months and a further increase of 0.19 points at 12 months. These increases were similar within the treatment groups (p > 0.05). For MNA-SF, the analysis showed that there were no significant differences recorded over the data collection points after treatment intervention (p < 0.05).

CONCLUSION: Tooth replacement using conventional and functionally orientated treatment for the partially dentate elderly showed significant improvements in MNA score 12 months after intervention.

CLINICAL RELEVANCE: Prosthodontic rehabilitation may play an important role in the nutritional status of partially dentate elders.

Two-year survival of ART restorations placed in elderly patients: A randomised controlled clinical trial

OBJECTIVES: Older dentate adults are a high caries risk group who could potentially benefit from the use of the atraumatic restorative treatment (ART). This study aimed to compare the survival of ART and a conventional restorative technique (CT) using rotary instruments and a resin-modified glass-ionomer for restoring carious lesions as part of a preventive and restorative programme for older adults after 2 years.

METHODS: In this randomised controlled clinical trial, 99 independently living adults (65-90 years) with carious lesions were randomly allocated to receive either ART or conventional restorations. The survival of restorations was assessed by an independent and blinded examiner 6 months, 1 year and 2 years after restoration placement.

RESULTS: Ninety-six (67.6%) and 121 (76.6%) restorations were assessed in the ART and CT groups, respectively, after 2 years. The cumulative restoration survival percentages after 2 years were 85.4% in the ART and 90.9% in the CT group. No statistically significant between group differences were detected (p=0.2050, logistic regression analysis).

CONCLUSIONS: In terms of restoration survival, ART was as effective as a conventional restorative approach to treat older adults after 2 years. This technique could be a useful tool to provide dental care for older adults particularly in the non-clinical setting. (Trial Registration number: ISRCTN 76299321).

CLINICAL SIGNIFICANCE: The results of this study show that ART presented survival rates similar to conventional restorations in older adults. ART appears to be a cost-effective way to provide dental care to elderly patients, particularly in out of surgery facilities, such as nursing homes.

Implant-retained overdentures did not have a significant improvement in dietary intake

DESIGN: Randomised controlled trial.

INTERVENTION: Patients aged 65 or above edentate for a minimum of five years, with sufficient bone for two implants in the anterior mandible, were recruited. Those with systemic disease that contraindicated implants or had a low mini-mental state evaluation score were excluded. Patients in both groups had a standard maxillary complete denture fabricated. Patients randomised to the treatment group received a two-implant mandibular overdenture while those in the control group received a standard mandibular complete denture. Three 24-hour dietary recalls were collected by telephone interviews at baseline and at 12 months.

RESULTS: 255 patients were randomised: 128 received a standard complete denture (CD) and 127 a two-implant mandibular overdenture (IOD). 127 patients were available at 12-month follow up, 114 in the CD group and 103 in the IOD group. No significant between-group differences were found.

CONCLUSIONS: Although there is much evidence supporting the adoption of two-implant mandibular overdenture (IOD) treatment as the standard of care for edentate patients, this evidence does not include an improvement in dietary intake at one year for medically healthy independent edentate elders when given no specific dietary counselling.