An introduction to InP-based generic integration technology

Photonic integrated circuits (PICs) are considered as the way to make photonic systems or subsystems cheap and ubiquitous. PICs still are several orders of magnitude more expensive than their microelectronic counterparts, which has restricted their application to a few niche markets. Recently, a novel approach in photonic integration is emerging which will reduce the R&D and prototyping costs and the throughput time of PICs by more than an order of magnitude. It will bring the application of PICs that integrate complex and advanced photonic functionality on a single chip within reach for a large number of small and larger companies and initiate a breakthrough in the application of Photonic ICs. The paper explains the concept of generic photonic integration technology using the technology developed by the COBRA research institute of TU Eindhoven as an example, and it describes the current status and prospects of generic InP-based integration technology

An introduction to InP-based generic integration technology

Photonic integrated circuits (PICs) are considered as the way to make photonic systems or subsystems cheap and ubiquitous. PICs still are several orders of magnitude more expensive than their microelectronic counterparts, which has restricted their application to a few niche markets.Recently, a novel approach in photonic integration is emerging which will reduce the R&D and prototyping costs and the throughput time of PICs by more than an order of magnitude. It will bring the application of PICs that integrate complex and advanced photonic functionality on a single chip within reach for a large number of small and larger companies and initiate a breakthrough in the application of Photonic ICs. The paper explains the concept of generic photonic integration technology using the technology developed by the COBRA research institute of TU Eindhoven as an example, and it describes the current status and prospects of generic InP-based integration technology.Funding is acknowledged by the EU-projects ePIXnet, EuroPIC and PARADIGM and the Dutch projects NRC Photonics, MEMPHIS, IOP Photonic Devices and STW GTIP. Many others have contributed and the authors would like to thank other PARADIGM and EuroPIC partners for their help in discussions, particularly Michael Robertson (CIP).This is the final published version distributed under a Creative Commons Attribution License. It can also be viewed on the publisher's website at: http://iopscience.iop.org/0268-1242/29/8/08300

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

p53 autoantibodies in patients with malignant mesothelioma: stability through disease progression

Malignant mesothelioma (MM) generally occurs as a pleural tumour, related to the inhalation of asbestos fibres. It is highly aggressive and largely unresponsive to treatment. The incidence of MM is particularly high in Western Australia because of the extensive blue asbestos mining operations that occurred in the north of the state until 1966. MM is unusual in that mutations in the tumour suppressor gene p53 are rarely observed, whilst over-expression of p53 protein is common. As the level of antibodies directed against p53 is thought to be of prognostic value in some cancers and as MM is known to be immunogenic, we studied a cohort of Western Australian patients to determine the prevalence of anti-p53 antibodies and their value as diagnostic markers or prognostic indicators. 6/88 (7%) of patients had high titres (>2 SD above the mean of controls) of anti-p53 antibodies. There was no correlation between antibody titre and survival. Although 3/38 (8%) of sera obtained from patients exposed to asbestos but prior to a diagnosis of MM contained antibodies, the same proportion of sera obtained from patients exposed to asbestos but who remained disease free also contained antibodies (2/40; 8%). Sera collected sequentially demonstrated a profound temporal stability in the titre of anti-p53 antibodies in patients with MM throughout the course of their illness. These results show that anti-p53 antibodies are observed only at a low frequency in the sera of MM patients and where they do occur, their elicitation is an early event that may be unrelated to antigen load. The occurrence of anti-p53 antibodies does not serve as either a useful prognostic or diagnostic indicator in MM. © 2001 Cancer Research Campaign http://www.bjcancer.co

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Objective measures for the assessment of post-operative pain in bos indicus bull calves following castration

The aim of the study was to assess pain in Bos indicus bull calves following surgical castration. Forty-two animals were randomised to four groups: no castration (NC, n = 6); castration with pre-operative lidocaine (CL, n = 12); castration with pre-operative meloxicam (CM, n = 12); and, castration alone (C, n = 12). Bodyweight was measured regularly and pedometers provided data on activity and rest from day −7 (7 days prior to surgery) to 13. Blood was collected for the measurement of serum amyloid A (SAA), haptoglobin, fibrinogen, and iron on days 0, 3 and 6. Bodyweight and pedometry data were analysed with a mixed effect model. The blood results were analysed with repeated measure one-way analysis of variance (ANOVA). There was no treatment effect on bodyweight or activity. The duration of rest was greatest in the CM group and lowest in the C group. There was a significant increase in the concentrations of SAA, haptoglobin, and fibrinogen in all of the groups from day 0 to 3. Iron concentrations were not different at the time points it was measured. The results of this study suggest that animals rest for longer periods after the pre-operative administration of meloxicam. The other objective assessments measured in this study were not able to consistently differentiate between treatment groups

Projecting the effect of crop yield increases, dietary change and different price scenarios on land use under two different state security regimes

Peer reviewe

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

This is the final version of the article. Available from the publisher via the DOI in this record.Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways