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Showing papers by "University of Southern Denmark published in 2010"


Journal ArticleDOI
TL;DR: In this article, the authors summarized the basic principles and major achievements of plasmon guiding, and details the current state-of-the-art in subwavelength PLASmonic waveguides, passive and active nanoplasmonic components for the generation, manipulation and detection of radiation, and configurations for the nanofocusing of light.
Abstract: Recent years have seen a rapid expansion of research into nanophotonics based on surface plasmon–polaritons. These electromagnetic waves propagate along metal–dielectric interfaces and can be guided by metallic nanostructures beyond the diffraction limit. This remarkable capability has unique prospects for the design of highly integrated photonic signal-processing systems, nanoresolution optical imaging techniques and sensors. This Review summarizes the basic principles and major achievements of plasmon guiding, and details the current state-of-the-art in subwavelength plasmonic waveguides, passive and active nanoplasmonic components for the generation, manipulation and detection of radiation, and configurations for the nanofocusing of light. Potential future developments and applications of nanophotonic devices and circuits are also discussed, such as in optical signals processing, nanoscale optical devices and near-field microscopy with nanoscale resolution.

3,481 citations


Journal ArticleDOI
TL;DR: Genetic loci associated with body mass index map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor, which may provide new insights into human body weight regulation.
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

2,632 citations


Journal ArticleDOI
Josée Dupuis1, Josée Dupuis2, Claudia Langenberg, Inga Prokopenko3  +336 moreInstitutions (82)
TL;DR: It is demonstrated that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

2,022 citations


Journal ArticleDOI
TL;DR: This is the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre-KRAS selection era and confirmed that, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA population response rates confirmed that.
Abstract: Background Following the discovery that mutant KRAS is associated with resistance to anti-epidermal growth factor receptor (EGFR) antibodies, the tumours of patients with metastatic colorectal cancer are now profiled for seven KRAS mutations before receiving cetuximab or panitumumab. However, most patients with KRAS wild-type tumours still do not respond. We studied the effect of other downstream mutations on the efficacy of cetuximab in, to our knowledge, the largest cohort to date of patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab plus chemotherapy in the pre-KRAS selection era. Methods 1022 tumour DNA samples (73 from fresh-frozen and 949 from formalin-fixed, paraffin-embedded tissue) from patients treated with cetuximab between 2001 and 2008 were gathered from 11 centres in seven European countries. 773 primary tumour samples had sufficient quality DNA and were included in mutation frequency analyses; mass spectrometry genotyping of tumour samples for KRAS, BRAF, NRAS, and PIK3CA was done centrally. We analysed objective response, progression-free survival (PFS), and overall survival in molecularly defined subgroups of the 649 chemotherapy-refractory patients treated with cetuximab plus chemotherapy. Findings 40.0% (299/747) of the tumours harboured a KRAS mutation, 14.5% (108/743) harboured a PIK3CA mutation (of which 68.5% [74/108] were located in exon 9 and 20.4% [22/108] in exon 20), 4.7% (36/761) harboured a BRAF mutation, and 2.6% (17/644) harboured an NRAS mutation. KRAS mutants did not derive benefit compared with wild types, with a response rate of 6.7% (17/253) versus 35.8% (126/352; odds ratio [OR] 0.13, 95% CI 0.07-0.22; p<0.0001), a median PFS of 12. weeks versus 24 weeks (hazard ratio [HR] 1 98, 1.66-2.36; p<0.0001), and a median overall survival of 32 weeks versus 50 weeks (1.75, 1.47-2.09; p<0.0001). In KRAS wild types, carriers of BRAF and NRAS mutations had a significantly lower response rate than did BRAF and NRAS wild types, with a response rate of 8.3% (2/24) in carriers of BRAF mutations versus 38.0% in BRAF wild types (124/326; OR 0.15, 95% CI 0.02-0.51; p=0.0012); and 7.7% (1/13) in carriers of NRAS mutations versus 38.1% in NRAS wild types (110/289; OR 0.14, 0.007-0.70; p=0.013). PIK3CA exon 9 mutations had no effect, whereas exon 20 mutations were associated with a worse outcome compared with wild types, with a response rate of 0.0% (0/9) versus 36.8% (121/329; OR 0.00,0.00-0.89; p=0.029), a median PFS of 11.5 weeks versus 24 weeks (HR 2.52, 1.33-4.78; p=0.013), and a median overall survival of 34 weeks versus 51 weeks (3.29, 1.60-6.74; p=0.0057). Multivariate analysis and conditional inference trees confirmed that, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about outcome. Objective response rates in our series were 24.4% in the unselected population, 36.3% in the KRAS wild-type selected population, and 41.2% in the KRAS, BRAF, NRAS, and PIK3CA exon 20 wild-type population. Interpretation While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA,exon 20 mutations are significantly associated with a low response rate. Objective response rates could be improved by additional genotyping of BRAF, NRAS, and PIK3CA exon 20 mutations in a KRAS wild-type population.

1,940 citations


Journal ArticleDOI
08 Oct 2010-Science
TL;DR: Humans must modify their behavior or risk causing irreversible changes to life on Earth, as the damage done by humans to the nitrogen economy of the planet will persist for decades, possibly centuries, if active intervention and careful management strategies are not initiated.
Abstract: Atmospheric reactions and slow geological processes controlled Earth's earliest nitrogen cycle, and by ~2.7 billion years ago, a linked suite of microbial processes evolved to form the modern nitrogen cycle with robust natural feedbacks and controls. Over the past century, however, the development of new agricultural practices to satisfy a growing global demand for food has drastically disrupted the nitrogen cycle. This has led to extensive eutrophication of fresh waters and coastal zones as well as increased inventories of the potent greenhouse gas nitrous oxide (N(2)O). Microbial processes will ultimately restore balance to the nitrogen cycle, but the damage done by humans to the nitrogen economy of the planet will persist for decades, possibly centuries, if active intervention and careful management strategies are not initiated.

1,882 citations


Journal ArticleDOI
TL;DR: By combining genome-wide association data from 8,130 individuals with type 2 diabetes and 38,987 controls of European descent and following up previously unidentified meta-analysis signals, 12 new T2D association signals are identified with combined P < 5 × 10−8.
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

1,785 citations


Journal ArticleDOI
TL;DR: In this article, the authors reviewed the research contributions of innovation in tourism and identified the important determinants of innovation, including the role of entrepreneurship, technology push and the existence of territorial industry clusters.

1,228 citations


Journal ArticleDOI
Iris M. Heid1, Anne U. Jackson2, Joshua C. Randall3, Tthomas W. Winkler1  +352 moreInstitutions (90)
TL;DR: A meta-analysis of genome-wide association studies for WHR adjusted for body mass index provides evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

869 citations


Journal ArticleDOI
TL;DR: No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation, and a multicentre study is needed to establish whether this effect can be reproduced in other facilities.

708 citations


Journal ArticleDOI
TL;DR: The data strongly suggest that the cold-induced emergence of brown adipocytes in WAT predominantly reflects beta(3)-adrenoceptor-mediated transdifferentiation.
Abstract: The origin of brown adipocytes arising in white adipose tissue (WAT) after cold acclimatization is unclear. Here, we demonstrate that several UCP1-immunoreactive brown adipocytes occurring in WAT a...

684 citations


Journal ArticleDOI
Richa Saxena1, Richa Saxena2, Claudia Langenberg, Toshiko Tanaka3  +170 moreInstitutions (52)
TL;DR: A meta-analysis of nine genome-wide association studies and a follow-up of 29 independent loci found three newly implicated loci to be associated with type 2 diabetes: GIPR, ADCY5 and VPS13C.
Abstract: Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).

Journal ArticleDOI
TL;DR: Strength training appears to elicit effective countermeasures in elderly individuals even at a very old age by evoking muscle hypertrophy along with substantial changes in neuromuscular function, respectively, and leads to an improved functional capacity during activities of daily living.
Abstract: Aging is characterized by loss of spinal motor neurons (MNs) due to apoptosis, reduced insulin-like growth factor I signaling, elevated amounts of circulating cytokines, and increased cell oxidative stress. The age-related loss of spinal MNs is paralleled by a reduction in muscle fiber number and size (sarcopenia), resulting in impaired mechanical muscle performance that in turn leads to a reduced functional capacity during everyday tasks. Concurrently, maximum muscle strength, power, and rate of force development are decreased with aging, even in highly trained master athletes. The impairment in muscle mechanical function is accompanied and partly caused by an age-related loss in neuromuscular function that comprise changes in maximal MN firing frequency, agonist muscle activation, antagonist muscle coactivation, force steadiness, and spinal inhibitory circuitry. Strength training appears to elicit effective countermeasures in elderly individuals even at a very old age (>80 years) by evoking muscle hypertrophy along with substantial changes in neuromuscular function, respectively. Notably, the training-induced changes in muscle mass and nervous system function leads to an improved functional capacity during activities of daily living.

Journal ArticleDOI
03 Dec 2010-Science
TL;DR: It is shown that both sulfate reduction and sulfide oxidation contribute to energy flux and elemental cycling in oxygen-free waters off the coast of northern Chile, suggesting that it may influence biogeochemical cycling in the global ocean.
Abstract: Nitrogen cycling is normally thought to dominate the biogeochemistry and microbial ecology of oxygen-minimum zones in marine environments. Through a combination of molecular techniques and process rate measurements, we showed that both sulfate reduction and sulfide oxidation contribute to energy flux and elemental cycling in oxygen-free waters off the coast of northern Chile. These processes may have been overlooked because in nature, the sulfide produced by sulfate reduction immediately oxidizes back to sulfate. This cryptic sulfur cycle is linked to anammox and other nitrogen cycling processes, suggesting that it may influence biogeochemical cycling in the global ocean.

Journal ArticleDOI
TL;DR: In this paper, case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate, and two previously identified regions (at chromosome 8q24 and IRF6) attained genomewide significance.
Abstract: Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 x 10(-12)) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development.

Journal ArticleDOI
TL;DR: An overview of the prescription databases established in the Nordic countries is presented, as well as to elaborate on their unique potential for record linkage and cross-national comparison of drug utilization, to assist in resolving safety issues of international interest.
Abstract: The Nordic countries have a long tradition of registry-based epidemiological research. Many population-based health registries were established in the 1960s, with use of unique personal identifiers facilitating linkage between registries. In recent years, each country has established a national database to track prescription drugs dispensed to individuals in ambulatory care. The objectives were to present an overview of the prescription databases established in the Nordic countries, as well as to elaborate on their unique potential for record linkage and cross-national comparison of drug utilization. Five Nordic countries collect drug exposure data based on drugs dispensed at pharmacies and have the potential to link these data to health outcomes. The databases together cover 25 million inhabitants (Denmark: 5.5 million; Finland: 5.3 million; Iceland: 0.3 million; Norway: 4.8 million; and Sweden: 9.2 million). In 2007, the registries encompassed 17 million prescription drug users (68% of the total population). We provide examples of how these databases have been used for descriptive drug utilization studies and analytical pharmacoepidemiological studies linking drug exposure to other health registries. Comparisons are facilitated by many similarities among the databases, including data source, content, coverage and methods used for drug utilization studies and record linkage. There are, however, some differences in coding systems and validity, as well as in some access and technical issues. To perform cross-national pharmacoepidemiological studies, resources, networks and time are needed, as well as methods for pooling data. Interpretation of results needs to account for inter-country heterogeneity and the possibility of spurious relationships. The Nordic countries have a unique potential for collaborative high-quality cross-national pharmacoepidemiological studies with large populations. This research may assist in resolving safety issues of international interest, thus minimizing the risk of either over-reacting on possible signals or underestimating drug safety issues.

Journal ArticleDOI
TL;DR: Recommendations are provided to improve information exchange on newly developed serum-free media and the formulation of a basic serum- free medium is suggested.

Journal ArticleDOI
TL;DR: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission in patients with rheumatoid arthritis.
Abstract: Objective To compare tumor necrosis factor α inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. Methods The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). Results Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52–2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28–2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82–1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63–2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15–1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20–1.80). Conclusion Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.

Journal ArticleDOI
TL;DR: In this article, the authors provided a comprehensivesynthesis of available data to obtain a better understanding of the relative contribution of seagrass and other possible sources of organic matter that accumulate in the sediment of the seafloor seagranthus meadows.
Abstract: Seagrass meadows are highly productive habitats found along many of the world’scoastline, providing important services that support the overall functioning of the coastalzone. The organic carbon that accumulates in seagrass meadows is derived not only fromseagrass production but from the trapping of other particles, as the seagrass canopiesfacilitate sedimentation and reduce resuspension. Here we provide a comprehensivesynthesis of the available data to obtain a better understanding of the relative contributionof seagrass and other possible sources of organic matter that accumulate in the sedimentsof seagrass meadows. The data set includes 219 paired analyses of the carbon isotopiccomposition of seagrass leaves and sediments from 207 seagrass sites at 88 locationsworldwide. Using a three source mixing model and literature values for putative sources,we calculate that the average proportional contribution of seagrass to the surfacesediment organic carbon pool is ∼50%. When using the best available estimates ofcarbon burial rates in seagrass meadows, our data indicate that between 41 and66 gC m

Journal ArticleDOI
28 Jan 2010-Nature
TL;DR: In this article, heat shock protein 70 (Hsp70) is shown to stabilize lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for acid sphingomyelin metabolism.
Abstract: Heat shock protein 70 (Hsp70) is an evolutionarily highly conserved molecular chaperone that promotes the survival of stressed cells by inhibiting lysosomal membrane permeabilization, a hallmark of stress-induced cell death. Clues to its molecular mechanism of action may lay in the recently reported stress- and cancer-associated translocation of a small portion of Hsp70 to the lysosomal compartment. Here we show that Hsp70 stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential co-factor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (Trp90Phe), as well as the pharmacological and genetic inhibition of ASM, effectively revert the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease (NPD) A and B-severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase 1 gene (SMPD1) encoding for ASM-is also associated with a marked decrease in lysosomal stability, and this phenotype can be effectively corrected by treatment with recombinant Hsp70. Taken together, these data open exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway.

Journal ArticleDOI
TL;DR: Findings show SIRT3 regulates ketone body production during fasting and provide molecular insight into how protein acetylation can regulate enzymatic activity.

Journal ArticleDOI
TL;DR: It is argued that the study of twin pairs discordant on exposure, and in particular discordant monozygotic twins, provides a useful analog to the idealized counterfactual design and is concluded that twin researchers could make greater use of the discordant-twin design to strengthen causal inferences in observational research.
Abstract: Valid causal inference is central to progress in theoretical and applied psychology. Although the randomized experiment is widely considered the gold standard for determining whether a given exposure increases the likelihood of some specified outcome, experiments are not always feasible and in some cases can result in biased estimates of causal effects. Alternatively, standard observational approaches are limited by the possibility of confounding, reverse causation, and the nonrandom distribution of exposure (i.e., selection). We describe the counterfactual model of causation and apply it to the challenges of causal inference in observational research, with a particular focus on aging. We argue that the study of twin pairs discordant on exposure, and in particular discordant monozygotic twins, provides a useful analog to the idealized counterfactual design. A review of discordant-twin studies in aging reveals that they are consistent with, but do not unambiguously establish, a causal effect of lifestyle factors on important late-life outcomes. Nonetheless, the existing studies are few in number and have clear limitations that have not always been considered in interpreting their results. It is concluded that twin researchers could make greater use of the discordant-twin design as one approach to strengthen causal inferences in observational research.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the association between potential predictor factors and visits to green space at least a few times per week and found that 66.9% of the respondents live within 300 m of green space, 43.0% visit green space every day and 91.5% visit Green Space at least once a week.

Journal ArticleDOI
12 Jan 2010-BMJ
TL;DR: In this article, individual patient data analysis using pooled data from randomised trials was performed to identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and assess the influence of dosing regimens and co-administration of calcium.
Abstract: Objectives: To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design: Individual patient data analysis using pooled data from randomised trials. Data sources: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis: Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion: This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.

Journal ArticleDOI
TL;DR: The isotopic composition and concentration of molybdenum in sedimentary rocks are used to couple the redox history of the atmosphere and oceans to major events in animal evolution, suggesting two episodes of global ocean oxygenation and suggesting that early metazoans evolved in a relatively low oxygen environment.
Abstract: The evolution of Earth’s biota is intimately linked to the oxygenation of the oceans and atmosphere. We use the isotopic composition and concentration of molybdenum (Mo) in sedimentary rocks to explore this relationship. Our results indicate two episodes of global ocean oxygenation. The first coincides with the emergence of the Ediacaran fauna, including large, motile bilaterian animals, ca. 550–560 million year ago (Ma), reinforcing previous geochemical indications that Earth surface oxygenation facilitated this radiation. The second, perhaps larger, oxygenation took place around 400 Ma, well after the initial rise of animals and, therefore, suggesting that early metazoans evolved in a relatively low oxygen environment. This later oxygenation correlates with the diversification of vascular plants, which likely contributed to increased oxygenation through the enhanced burial of organic carbon in sediments. It also correlates with a pronounced radiation of large predatory fish, animals with high oxygen demand. We thereby couple the redox history of the atmosphere and oceans to major events in animal evolution.

Journal ArticleDOI
TL;DR: In this paper, the authors developed a multi echelon, multi period, multi product closed loop supply chain network model for product returns and the decisions are made regarding material procurement, production, distribution, recycling and disposal.

Journal ArticleDOI
TL;DR: Interestingly, these analyses show that PPARγ and C/EBPα binding sites are associated with most genes that are induced during adipogenesis suggesting direct activation of many more adipocyte genes than previously anticipated.

Journal ArticleDOI
TL;DR: In this article, the authors used iron and sulphur systematics to reconstruct oceanic redox conditions from the 1.88- to 1.83-billion-year-old Animikie group from the Superior region, North America, finding that surface waters were oxygenated, whereas at mid-depths, anoxic and sulphidic (euxinic) conditions extended over 100 km from the palaeoshoreline.
Abstract: The deposition of iron formations ceased about 1.84 billion years ago. Reconstructions of ocean chemistry suggest that the advent of euxinic conditions along ocean margins preferentially removed dissolved iron from the water column in the form of the mineral pyrite, inhibiting widespread iron-oxide mineral deposition. The evolution of ocean chemistry during the Proterozoic eon (2.5–0.542 billion years ago) is thought to have played a central role in both the timing and rate of eukaryote evolution1,2. The timing of the deposition of iron formations implies that, early in the Earth’s history, oceans were predominantly anoxic and rich in dissolved iron3. However, global deposition of iron formations ceased about 1.84 billion years ago. This termination indicates a major upheaval in ocean chemistry4, but the precise nature of this change remains debated5,6,7,8. Here we use iron and sulphur systematics to reconstruct oceanic redox conditions from the 1.88- to 1.83-billion-year-old Animikie group from the Superior region, North America. We find that surface waters were oxygenated, whereas at mid-depths, anoxic and sulphidic (euxinic) conditions extended over 100 km from the palaeoshoreline. The spatial extent of euxinia varied through time, but deep ocean waters remained rich in dissolved iron. Widespread euxinia along continental margins would have removed dissolved iron from the water column through the precipitation of pyrite, which would have reduced the supply of dissolved iron and resulted in the global cessation of the deposition of ‘Superior-type’ iron formations. We suggest that incursions of sulphide from the mid-depths into overlying oxygenated surface waters may have placed severe constraints on eukaryotic evolution.

Journal ArticleDOI
TL;DR: An association between distance to a green space and health and health-related quality of life was found and indicates awareness among Danes that green spaces may be of importance in managing stress and that green Spaces may play an important role as health-promoting environments.
Abstract: Aims: To investigate the associations between green space and health, health-related quality of life and stress, respectively. Methods: Data were derived from the 2005 Danish Health Interview Survey and are based on a region-stratified random sample of 21,832 adults. Data were collected via face-to-face interviews followed by a self-administered questionnaire, including the SF-36, which measures eight dimensions of health and the Perceived Stress Scale, which measures self-reported stress. A total of 11,238 respondents completed the interview and returned the questionnaire. Multiple logistic regression analyses were performed to investigate the association between distance to green space and self-perceived stress. Results: Danes living more than 1 km away from the nearest green space report poorer health and health-related quality of life, i.e. lower mean scores on all eight SF-36 dimensions of health than respondents living closer. Respondents living more than 1 km away from a green space have 1.42 highe...

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TL;DR: In this article, a review of the separation technologies used for animal slurry treatment and the physical and chemical processes involved in separation is presented, and a simple separation efficiency expression can be used to assess the efficiency of slurry separation.
Abstract: Animal slurry contains plant nutrients that are essential for crop production. However, intensive livestock production may lead to a surplus of plant nutrients on farms and, as a consequence, discharge or emission to the environment. In order to ensure that the slurry applied to fields matches the nutrient requirements of the crops, techniques have been developed to reduce the nutrient content of slurry by means of separation. This review discusses the separation technologies used for animal slurry treatment and the physical and chemical processes involved in separation. These processes need to be understood before efficient, reliable and cheap separation technologies that take into account the actual properties of slurry and the likely end-use of the separation products can be developed. A simple separation efficiency expression can be used to assess the efficiency of slurry separation. It is indeed important to measure the amount and composition of the slurry before treatment, the dry-matter-rich fraction and the liquid fraction. The separation efficiency of mechanical separators for the removal of dry matter and phosphorus (P) is ranked as follows: centrifugation > sedimentation > non-pressurized filtration > pressurized filtration. In general, the separation of total N and NH + follows the same pattern, but the separation efficiency is lower than for dry matter and P. Treatment with a flocculant before separation improves separation efficiency significantly. Of the polyacrylamide polymers tested, high-molecular-weight, linear cationic polymers with a medium charge density (20-40 mol%) were found to be the most efficient flocculants. The best mechanical separation techniques for flocculated slurry are screens or filter belts. The separation efficiency of polyacrylamide-treated slurry can be improved by adding a multivalent ion to coagulate particles and for precipitation of phosphorus. Aluminium sulfate (Al2(SO4)3 )o r ferric chloride (FeCl 3) seem to be very efficient for improving the mechanical separators. Alternatively, the mineral struvite (MgNH4PO4) may be formed by changing the slurry characteristics, such as by the addition of magnesium (Mg) or by increasing the pH to 9. The struvite crystals are removed during solid-liquid separation. The products of the solid-liquid separation may be further treated by evaporation, membrane filtration or ammonia stripping in order to obtain the desired end-products; however, low-maintenance and/or cost-efficient operation of these post-treatments has not yet been demonstrated. The separation should be developed as a whole-system approach, paying attention to parameters such as the value of end-products, environmental consequences and economy.

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TL;DR: In this article, a case study of the Danish national 49er sailing team is presented, where the authors focus on the overall athletic talent development environment (ATDE) and examine key factors behind its success in creating top athletes.