Showing papers by "University of Iceland published in 2008"

Large recurrent microdeletions associated with schizophrenia

Abstract: Reduced fecundity, associated with severe mental disorders, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism, schizophrenia and mental retardation. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation and autism. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

Abstract: Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

Spectral and Spatial Classification of Hyperspectral Data Using SVMs and Morphological Profiles

Abstract: A method is proposed for the classification of urban hyperspectral data with high spatial resolution. The approach is an extension of previous approaches and uses both the spatial and spectral information for classification. One previous approach is based on using several principal components (PCs) from the hyperspectral data and building several morphological profiles (MPs). These profiles can be used all together in one extended MP. A shortcoming of that approach is that it was primarily designed for classification of urban structures and it does not fully utilize the spectral information in the data. Similarly, the commonly used pixelwise classification of hyperspectral data is solely based on the spectral content and lacks information on the structure of the features in the image. The proposed method overcomes these problems and is based on the fusion of the morphological information and the original hyperspectral data, i.e., the two vectors of attributes are concatenated into one feature vector. After a reduction of the dimensionality, the final classification is achieved by using a support vector machine classifier. The proposed approach is tested in experiments on ROSIS data from urban areas. Significant improvements are achieved in terms of accuracies when compared to results obtained for approaches based on the use of MPs based on PCs only and conventional spectral classification. For instance, with one data set, the overall accuracy is increased from 79% to 83% without any feature reduction and to 87% with feature reduction. The proposed approach also shows excellent results with a limited training set.

A multi-temporal InSAR method incorporating both persistent scatterer and small baseline approaches

Abstract: Synthetic aperture radar (SAR) interferometry is a technique that provides high-resolution measurements of the ground displacement associated with many geophysical processes. Advanced techniques involving the simultaneous processing of multiple SAR acquisitions in time increase the number of locations where a deformation signal can be extracted and reduce associated error. Currently there are two broad categories of algorithms for processing multiple acquisitions, persistent scatterer and small baseline methods, which are optimized for different models of scattering. However, the scattering characteristics of real terrains usually lay between these two end-member models. I present here a new method that combines both approaches, to extract the deformation signal at more points and with higher overall signal-to-noise ratio than can either approach alone. I apply the combined method to data acquired over Eyjafjallajokull volcano in Iceland, and detect time-varying ground displacements associated with two intrusion events.

Birth Weight and Risk of Type 2 Diabetes: A Systematic Review

Abstract: Context Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. Objective To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. Data Sources and Study Selection Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. Data Extraction Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. Data Synthesis Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight–type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I 2 = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight–type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. Conclusion In most populations studied, birth weight was inversely related to type 2 diabetes risk.

The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Abstract: Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation

Abstract: Objectives: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. Material and Methods: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. Results: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37‐4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4‐96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21‐11.38%), translating to 10.5% (95% CI: 3.6‐28.9%) of the subjects experiencing implant loss over 3 years. Conclusion: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively.

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

Abstract: Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two populationbased cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The yearto-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28–0.53, over 4 y, and 0.35, 95% CI 0.23–0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29–1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45–3.15) with long-term average (‘‘usual’’) IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42–1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45–4.56] per 2 SD increase in usual [long-term average] IL-6 levels).

The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli

Abstract: The number and scope of methods developed to interrogate and use metabolic network reconstructions has significantly expanded over the past 15 years. In particular, Escherichia coli metabolic network reconstruction has reached the genome scale and been utilized to address a broad spectrum of basic and practical applications in five main categories: metabolic engineering, model-directed discovery, interpretations of phenotypic screens, analysis of network properties and studies of evolutionary processes. Spurred on by these accomplishments, the field is expected to move forward and further broaden the scope and content of network reconstructions, develop new and novel in silico analysis tools, and expand in adaptation to uses of proximal and distal causation in biology. Taken together, these efforts will solidify a mechanistic genotype-phenotype relationship for microbial metabolism.

Mineral Carbonation of CO2

Abstract: A survey of the global carbon reservoirs suggests that the most stable, long-term storage mechanism for atmospheric CO2 is the formation of carbonate minerals such as calcite, dolomite and magnesite. The feasibility is demonstrated by the proportion of terrestrial carbon bound in these minerals: at least 40,000 times more carbon is present in carbonate rocks than in the atmosphere. Atmospheric carbon can be transformed into carbonate minerals either ex situ, as part of an industrial process, or in situ, by injection into geological formations where the elements required for carbonate-mineral formation are present. Many challenges in mineral carbonation remain to be resolved. They include overcoming the slow kinetics of mineral-fluid reactions, dealing with the large volume of source material required and reducing the energy needed to hasten the carbonation process. To address these challenges, several pilot studies have been launched, including the CarbFix program in Iceland. The aim of CarbFix is to inject CO2 into permeable basaltic rocks in an attempt to form carbonate minerals directly through a coupled dissolution-precipitation process.

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions.

Abstract: Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).

Solid Lipid Nanoparticles as Delivery Systems for Bioactive Food Components

Abstract: The inclusion of bioactive compounds, such as carotenoids, omega-3 fatty acids, or phytosterols, is an essential requisite for the production of functional foods designed to improve the long-term health and well-being of consumers worldwide. To incorporate these functional components successfully in a food system, structurally sophisticated encapsulation matrices have to be engineered, which provide maximal physical stability, protect ingredients against chemical degradation, and allow for precise control over the release of encapsulated components during mastication and digestion to maximize adsorption. A novel encapsulation system initially developed in the pharmaceutical industries to deliver lipophilic bioactive compounds is solid lipid nanoparticles (SLN). SLN consist of crystallized nanoemulsions with the dispersed phase being composed of a solid carrier lipid–bioactive ingredient mixture. Contrary to larger colloidal solid lipid particles, specific crystal structures can be “dialed-in” in SLN by using specific surfactant mixtures and ensuring that mean particle sizes are below 100–200 nm. Moreover, in SLN, microphase separations of the bioactive compound from the solidifying lipid matrix can be prevented resulting in an even dispersion of the encapsulated compound in the solid matrix thereby improving chemical and physical stability of the bioactive. In this review article, we will briefly introduce the structure, properties, stability, and manufacturing of solid lipid particles and discuss their emerging use in food science.

Sequence Variant on 8q24 Confers Susceptibility to Urinary Bladder Cancer

Abstract: We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7)).

Standardizing assessment of elderly people in acute care: the interRAI Acute Care instrument.

Abstract: OBJECTIVES: To examine the frequency distributions and interrater reliability of individual items of the interRAI Acute Care instrument DESIGN: Observational study of a representative sample of older inpatients; duplicate assessments conducted on a subsample by independent assessors to examine interrater reliability SETTING: Acute medical, acute geriatric and orthopedic units in 13 hospitals in nine countries PARTICIPANTS: Five hundred thirty-three patients aged 70 and older (mean age 824, range 70–102) with an anticipated stay of 48 hours or longer of whom 161 received duplicate assessments MEASUREMENTS: Sixty-two clinical items across 11 domains Premorbid (3-day observation period before onset of the acute illness) and admission (the first 24 hours of hospital stay) assessments were conducted RESULTS: The frequency of deficits exceeded 30% for most items, ranging from 1% for physically abusive behavior to 86% for the need for support in activities of daily living after discharge Common deficits were in cognitive skills for daily decision-making (38% premorbid, 54% at admission), personal hygiene (37%, 65%), and walking (39%, 71%) Interrater reliability was substantial in the premorbid period (average κ=061) and admission period (average κ=066) Of the 69 items tested, less than moderate agreement (κ 08) for nine (13%) CONCLUSION: Initial assessment of the psychometric properties of the interRAI Acute Care instrument provided evidence that item selection and interrater reliability are appropriate for clinical application Further studies are required to examine the validity of embedded scales, diagnostic algorithms, and clinical protocols

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation. Part II: transalveolar technique.

Abstract: Objectives: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. Material and Methods: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. Results: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37–4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4–96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21–11.38%), translating to 10.5% (95% CI: 3.6–28.9%) of the subjects experiencing implant loss over 3 years. Conclusion: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively.

Positive Development in Adolescence: The Development and Role of Intentional Self-Regulation.

Abstract: Adolescence is a period of marked change in the person’s cognitive, physical, psychological, and social development and in the individual’s relations with the people and institutions of the social wor

Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke

Abstract: Objective To find sequence variants that associate with the risk for ischemic stroke (IS), we performed a genome-wide association study. Methods We genotyped 1,661 Icelandic IS patients and 10,815 control subjects using the Infinium HumanHap300 chip (Illumina, San Diego, CA). A total of 310,881 single nucleotide polymorphisms (SNPs) were tested for association with IS, and the most significant signals were replicated in two large European IS sample sets (2,224 cases/2,583 control subjects). Two SNPs, rs2200733 and rs10033464, were tested further in additional European IS samples (2,327 patients and 16,760 control subjects). Results In the Icelandic samples and the two replication sets combined, rs2200733 associated significantly with cardioembolic stroke (CES) (odds ratio [OR], 1.54; p = 8.05 × 10−9). No other variants associated with IS or any of its subtypes. rs2200733 associated significantly with IS in all sample sets combined (OR, 1.26; p = 2.18 × 10−10), and both rs2200733 and its neighbour, rs10033464 associated strongly with CES (rs2200733: OR, 1.52; p = 5.8 × 10−12; rs10033464: OR, 1.27; p = 6.1 × 10−4). Interestingly, rs2200733 also showed significant association to IS not classified as CES. Interpretation We discovered that variants previously shown to associate with atrial fibrillation (AF), rs2200733 and rs10033464, significantly associated with IS, with the strongest risk for CES. The association with noncardiogenic stroke is intriguing and suggests that atrial fibrillation may be underdiagnosed in patients presenting with stroke. This discovery may have implications for workup and treatment of IS. Ann Neurol 2008;64:402–409

Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data.

Abstract: Background Large-scale prospective data are needed to determine whether associations between lipoprotein(a) (Lp[a]) and coronary heart disease (CHD) risk are independent of established risk factors, to characterize the shape of this relationship, and to quantify associations in relevant subgroups. Methods Levels of Lp(a) were measured in samples obtained at baseline from 2047 patients who had first-ever nonfatal myocardial infarction or who died of CHD during the study and from 3921 control participants in the Reykjavik Study (n = 18 569), as well as in paired samples obtained 12 years apart from 372 participants to quantify within-person fluctuations. Results Baseline Lp(a) levels had little or no correlation with known cardiovascular risk factors, such as age, sex, total cholesterol level, and blood pressure. The Lp(a) values were highly consistent from decade to decade, with a regression dilution ratio (calculated on the log scale) of 0.92 (95% confidence interval, 0.85-0.99). The odds ratio for CHD, unaltered after adjustment for several established risk factors (age, sex, smoking status, blood pressure, total cholesterol, triglycerides level, diabetes mellitus, and body mass index), was 1.60 (95% confidence interval, 1.38-1.85) in a comparison of extreme thirds of baseline Lp(a) levels. Odds ratios were progressively higher with increasing Lp(a) levels and did not vary materially by several individual- or study-level characteristics. Conclusions There are independent, continuous associations between Lp(a) levels and risk of future CHD in a broad range of individuals. Levels of Lp(a) are highly stable within individuals across many years and are only weakly correlated with known risk factors. Further assessment of their possible role in CHD prevention is warranted.

Risk of second primary cancer among patients with head and neck cancers: A pooled analysis of 13 cancer registries

Abstract: The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age-, sex- and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking.

Novel MITF Targets Identified Using a Two-Step DNA Microarray Strategy

Abstract: Malignant melanoma is a chemotherapy-resistant cancer with high mortality. Recent advances in our understanding of the disease at the molecular level have indicated that it shares many characteristics with developmental precursors to melanocytes, the mature pigment-producing cells of the skin and hair follicles. The development of melanocytes absolutely depends on the action of the microphthalmia-associated transcription factor (MITF). MITF has been shown to regulate a broad variety of genes, whose functions range from pigment production to cell-cycle regulation, migration and survival. However, the existing list of targets is not sufficient to explain the role of MITF in melanocyte development and melanoma progression. DNA microarray analysis of gene expression offers a straightforward approach to identify new target genes, but standard analytical procedures are susceptible to the generation of false positives and require additional experimental steps for validation. Here, we introduce a new strategy where two DNA microarray-based approaches for identifying transcription factor targets are combined in a cross-validation protocol designed to help control false-positive generation. We use this two-step approach to successfully re-identify thirteen previously recorded targets of MITF-mediated upregulation, as well as 71 novel targets. Many of these new targets have known relevance to pigmentation and melanoma biology, and further emphasize the critical role of MITF in these processes.

Plate boundaries, rifts and transforms in Iceland

Abstract: The Iceland hotspot has a pronounced effect on the appearance and structure of the plate boundary between the North America and Eurasia Plates that crosses the island. The thick crust produced by the excess magmatism of the hotspot leads to a wider and more complicated plate boundary deformation zone than is observed along normal oceanic plate boundaries. Furthermore, the relative movement of the boundary with re- spect to the roots of the hotspot leads to unstable boundaries and rift jumps, when crustal blocks or microplates are transferred from one major plate to the other. The plate boundary zone can be divided into segments that are physiographically relatively homogeneous and possess distinct tectonic characteristics. The segments are more or less oblique to the relative spreading direction of the two major plates. The divergent componentof the movements is taken up by diking and normal faulting and is usually concentrated in the fissure swarms of the volcanic systems. The transcurrent component of the movements is often accommodated by strike-slip faulting on faults that are transverse to the plate boundary segment, so-called bookshelf faults, witnessing to the tran- sient nature of the segments. In highly oblique segments, such as the Reykjanes Peninsula Rift and the Grimsey Oblique Rift, both types of active structures occur superimposed on each other. In the South Iceland Seismic Zone, that is almost parallel to the local spreading direction, the bookshelf faults dominate the structure, pro- ducing earthquakes as large as magnitude 7. More mature transform zones, such as the Husavik-Flatey faults, have developed strike-slip faults that are sub-parallel to the plate movements. The activity on this transform zone, however, appears to be declining because of transfer of movement over to the Grimsey zone. This is supported by the lack of Holocene volcanism along the Eyjafjarðarall Rift that connects the transform to the Kolbeinsey Ridge plate boundary off shore. A ridge-jump appears to be in progress in South Iceland, where rifting is occurring in two sub-parallel rift zones, the very active Eastern Volcanic Zone and the less active Western Volcanic Zone. The block between them is seismically and volcanically inert and may be defined as a microplate, the Hreppar Microplate. It is rotating in response to the southward propagation of the Eastern Volcanic Zone and corresponding recess of the Western Volcanic Zone. Poles of relative rotation with respect to the North America and Eurasia Plates are suggested near 65.2 ◦ N, 20.1 ◦ W, and 62.8 ◦ N, 21.3 ◦ W, respectively.

Optical circuits based on polariton neurons in semiconductor microcavities.

Abstract: By exploiting the polarization multistability of polaritons, we show that polarized signals can be conducted in the plane of a semiconductor microcavity along controlled channels or "neurons." Furthermore, because of the interaction of polaritons with opposite spins it is possible to realize binary logic gates operating on the polarization degree of freedom. Multiple gates can be integrated together to form an optical circuit contained in a single semiconductor microcavity.

Obesity in psoriasis: leptin and resistin as mediators of cutaneous inflammation.

Abstract: Summary Background Obesity is a significant risk factor for psoriasis and body mass index (BMI) correlates with disease severity. Objectives To investigate the relationship between obesity and psoriasis, focusing on the role of adipokines such as leptin and resistin. Patients/methods Patients with psoriasis (n = 30) were recruited and their BMI, waist circumference and disease severity [Psoriasis Area and Severity Index (PASI)] were recorded. Fasting serum samples were obtained on enrolment and after a course of ultraviolet (UV) B treatment. Age-, sex- and BMI-matched healthy controls were also recruited. Results On enrolment, serum leptin and soluble leptin receptor levels were not raised compared with the controls. However, resistin, interleukin (IL)-1β, IL-6, and chemokines CCL2, CXCL8 and CXCL9 were all significantly elevated in the patient group and serum resistin correlated with disease severity (r = 0·372, P = 0·043). Improvement after UVB treatment was accompanied by decreased serum CXCL8. In vitro, both leptin and resistin could induce CXCL8 and tumour necrosis factor-α production by blood monocytes, and leptin could additionally induce IL-1β and IL-1 receptor antagonist production. Leptin also dose dependently increased secretion of the growth factor amphiregulin by ex vivo-cultured lesional psoriasis skin. Conclusions These data support the view that leptin and resistin may be involved in the pathogenesis of psoriasis in overweight individuals, possibly by augmenting the cytokine expression by the inflammatory infiltrate.

Classifying Multilevel Imagery From SAR and Optical Sensors by Decision Fusion

Abstract: A strategy for the joint classification of multiple segmentation levels from multisensor imagery is introduced by using synthetic aperture radar and optical data. At first, the two data sets are separately segmented, creating independent aggregation levels at different scales. Each individual level from the two sensors is then preclassified by a support vector machine (SVM). The original outputs of each SVM, i.e., images showing the distances of the pixels to the hyperplane fitted by the SVM, are used in a decision fusion to determine the final classes. The fusion strategy is based on the application of an additional classifier, which is applied on the preclassification results. Both a second SVM and random forests (RF) were tested for the decision fusion. The results are compared with SVM and RF applied to the full data set without preclassification. Both the integration of multilevel information and the use of multisensor imagery increase the overall accuracy. It is shown that the classification of multilevel-multisource data sets with SVM and RF is feasible and does not require a definition of ideal aggregation levels. The proposed decision fusion approach that applies RF to the preclassification outperforms all other approaches.

Prosthetic treatment planning on the basis of scientific evidence.

Abstract: The objective of this report is to summarize the results on survival and complication rates of different designs of fixed dental prostheses (FDP) published in a series of systematic reviews. Moreover, the various parameters for survival and risk assessment are to be used in attempt to perform treatment planning on the basis of scientific evidence. Three electronic searches complemented by manual searching were conducted to identify prospective and retrospective cohort studies on FDP and implant-supported single crowns (SC) with a mean follow-up time of at least 5 years. Patients had to have been examined clinically at the follow-up visit. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates of 5- and 10-year survival proportions. Meta-analysis of the studies included indicated an estimated 5-year survival of conventional tooth-supported FDP of 93.8%, cantilever FDP of 91.4%, solely implant-supported FDP of 95.2%, combined tooth-implant-supported FDP of 95.5% and implant-supported SC of 94.5% as well as resin-bonded bridges 87.7%. Moreover, after 10 years of function the estimated survival decreased to 89.2% for conventional FDP, to 80.3% for cantilever FDP, to 86.7% for implant-supported FDP, to 77.8% for combined tooth-implant-supported FDP, to 89.4% for implant-supported SC and to 65% for resin-bonded bridges. When planning prosthetic rehabilitations, conventional end-abutment tooth-supported FDP, solely implant-supported FDP or implant-supported SC should be the first treatment option. Only as a second option, because of reasons such as financial aspects patient-centered preferences or anatomical structures cantilever tooth-supported FDP, combined tooth-implant-supported FDP or resin-bonded bridges should be chosen.

The Artiodactyl APOBEC3 Innate Immune Repertoire Shows Evidence for a Multi-Functional Domain Organization that Existed in the Ancestor of Placental Mammals

Abstract: Background: APOBEC3 (A3) proteins deaminate DNA cytosines and block the replication of retroviruses and retrotransposons. Each A3 gene encodes a protein with one or two conserved zinccoordinating motifs (Z1, Z2 or Z3). The presence of one A3 gene in mice (Z2–Z3) and seven in humans, A3A-H (Z1a, Z2a-Z1b, Z2b, Z2c-Z2d, Z2e-Z2f, Z2g-Z1c, Z3), suggests extraordinary evolutionary flexibility. To gain insights into the mechanism and timing of A3 gene expansion and into the functional modularity of these genes, we analyzed the genomic sequences, expressed cDNAs and activities of the full A3 repertoire of three artiodactyl lineages: sheep, cattle and pigs. Results: Sheep and cattle have three A3 genes, A3Z1, A3Z2 and A3Z3, whereas pigs only have two, A3Z2 and A3Z3. A comparison between domestic and wild pigs indicated that A3Z1 was deleted in the pig lineage. In all three species, read-through transcription and alternative splicing also produced a catalytically active double domain A3Z2-Z3 protein that had a distinct cytoplasmic localization. Thus, the three A3 genes of sheep and cattle encode four conserved and active proteins. These data, together with phylogenetic analyses, indicated that a similar, functionally modular A3 repertoire existed in the common ancestor of artiodactyls and primates (i.e., the ancestor of placental mammals). This mammalian ancestor therefore possessed the minimal A3 gene set, Z1-Z2-Z3, required to evolve through a remarkable series of eight recombination events into the present day eleven Z domain human repertoire. Conclusion: The dynamic recombination-filled history of the mammalian A3 genes is consistent with the modular nature of the locus and a model in which most of these events (especially the expansions) were selected by ancient pathogenic retrovirus infections.