Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Essential Oil Composition of Diploid and Tetraploid Clones of Ginger (Zingiber officinale Roscoe) Grown in Australia

Ginger oil, obtained by steam distillation of the rhizome of Zingiber officinale Roscoe, is used in the beverage and fragrance industries. Ginger oil displays considerable compositional diversity, but is typically characterized by a high content of sesquiterpene hydrocarbons, including zingiberene, arcurcumene, â-bisabolene, and â-sesquiphellandrene. Australian ginger oil has a reputation for possessing a particular “lemony” aroma, due to its high content of the isomers neral and geranial, often collectively referred to as citral. Fresh rhizomes of 17 clones of Australian ginger, including commercial cultivars and experimental tetraploid clones, were steam distilled 7 weeks post-harvest, and the resulting oils were analyzed by GC-MS. The essential oils of 16 of the 17 clones, including the tetraploid clones and their parent cultivar, were found to be of substantially similar composition. These oils were characterized by very high citral levels (51-71%) and relatively low levels of the sesquiterpene hydrocarbons typical of ginger oil. The citral levels of most of these oils exceeded those previously reported for ginger oils. The neral-to-geranial ratio was shown to be remarkably constant (0.61 ( 0.01) across all 17 clones. One clone, the cultivar “Jamaican”, yielded oil with a substantially different composition, lower citral content and higher levels of sesquiterpene hydrocarbons. Because this cultivar also contains significantly higher concentrations of pungent gingerols, it possesses unique aroma and flavor characteristics, which should be of commercial interest.

Growth and species interactions of Eucalyptus pellita in a mixed and monoculture plantation in the humid tropics of north Queensland

This study investigated whether mixed-species designs can increase the growth of a tropical eucalypt when compared to monocultures. Monocultures of Eucalyptus pellita (E) and Acacia peregrina (A) and mixtures in various proportions (75E:25A, 50E:50A, 25E:75A) were planted in a replacement series design on the Atherton Tablelands of north Queensland, Australia. High mortality in the establishment phase due to repeated damage by tropical cyclones altered the trial design. Effects of experimental designs on tree growth were estimated using a linear mixed-effects model with restricted maximum likelihood analysis (REML). Volume growth of individual eucalypt trees were positively affected by the presence of acacia trees at age 5 years and this effect generally increased with time up to age 10 years. However, the stand volume and basal area increased with increasing proportions of E. pellita, due to its larger individual tree size. Conventional analysis did not offer convincing support for mixed-species designs. Preliminary individual-based modelling using a modified Hegyi competition index offered a solution and an equation that indicates acacias have positive ecological interactions (facilitation or competitive reduction) and definitely do not cause competition like a eucalypt. These results suggest that significantly increased in growth rates could be achieved with mixed-species designs. This statistical methodology could enable a better understanding of species interactions in similarly altered experiments, or undesigned mixed-species plantations.

Raman Spectroscopic study of valinomycin-metal complexes

Valinomycin, an ionophore of considerable interest for its ion selectivity, and its K+, Mg2+, Ba2+, and Ca2+ complexes were studied by Raman spectroscopy. Each complex has a characteristic spectrum which differs from that of uncomplexed valinomycin, suggesting several distinct structures for each of the metal-valinomycin complexes. The biologically active potassium complex shows the most significant changes in its spectrum, especially in the intensity of the symmetric C---H stretching vibration of CH3 and the convergence of the two ester carbonyl stretching vibration bands into one complex formation. These results are due to the unique orientation of the ester carbonyl groups toward the caged potassium ion and the resulting more free rotation of isopropyl side chains. The divalent cation-valinomycin complexes examined showed spectra which differed in each case uniquely from both valinomycin and its complex with potassium.

Effects of methyl eugenol feeding on mating compatibility of Asian population of Bactrocera dorsalis (Diptera: Tephritidae) with African population and with B. carambolae

Males of some species included in the Bactrocera dorsalis complex are strongly attracted to methyl eugenol (ME) (1,2-dimethoxy-4-(2-propenyl) benzene), a natural compound occurring in a variety of plant species. ME feeding of males of the B. dorsalis complex is known to enhance their mating competitiveness. Within B. dorsalis, recent studies show that Asian and African populations of B. dorsalis are sexually compatible, while populations of B. dorsalis and Bactrocera carambolae are relatively incompatible. The objectives of this study were to examine whether ME feeding by males affects mating compatibility between Asian and African populations of B. dorsalis and ME feeding reduces male mating incompatibility between B. dorsalis (Asian population) and B. carambolae. The data confirmed that Asian and African populations of B. dorsalis are sexually compatible for mating and showed that ME feeding only increased the number of matings. Though ME feeding also increased the number of matings of B. dorsalis (Asian population) and B. carambolae males but the sexual incompatibility between both species was not reduced by treatment with ME. These results conform to the efforts resolving the biological species limits among B. dorsalis complex and have implications for fruit fly control programs in fields and horticultural trade.

Trapping to monitor tephritid movement: Results, best practice, and assessment of alternatives

Movement of tephritid flies underpins their survival, reproduction, and ability to establish in new areas and is thus of importance when designing effective management strategies. Much of the knowledge currently available on tephritid movement throughout landscapes comes from the use of direct or indirect methods that rely on the trapping of individuals. Here, we review published experimental designs and methods from mark-release-recapture (MRR) studies, as well as other methods, that have been used to estimate movement of the four major tephritid pest genera (Bactrocera, Ceratitis, Anastrepha, and Rhagoletis). In doing so, we aim to illustrate the theoretical and practical considerations needed to study tephritid movement. MRR studies make use of traps to directly estimate the distance that tephritid species can move within a generation and to evaluate the ecological and physiological factors that influence dispersal patterns. MRR studies, however, require careful planning to ensure that the results obtained are not biased by the methods employed, including marking methods, trap properties, trap spacing, and spatial extent of the trapping array. Despite these obstacles, MRR remains a powerful tool for determining tephritid movement, with data particularly required for understudied species that affect developing countries. To ensure that future MRR studies are successful, we suggest that site selection be carefully considered and sufficient resources be allocated to achieve optimal spacing and placement of traps in line with the stated aims of each study. An alternative to MRR is to make use of indirect methods for determining movement, or more correctly, gene flow, which have become widely available with the development of molecular tools. Key to these methods is the trapping and sequencing of a suitable number of individuals to represent the genetic diversity of the sampled population and investigate population structuring using nuclear genomic markers or non-recombinant mitochondrial DNA markers. Microsatellites are currently the preferred marker for detecting recent population displacement and provide genetic information that may be used in assignment tests for the direct determination of contemporary movement. Neither MRR nor molecular methods, however, are able to monitor fine-scale movements of individual flies. Recent developments in the miniaturization of electronics offer the tantalising possibility to track individual movements of insects using harmonic radar. Computer vision and radio frequency identification tags may also permit the tracking of fine-scale movements by tephritid flies by automated resampling, although these methods come with the same problems as traditional traps used in MRR studies. Although all methods described in this chapter have limitations, a better understanding of tephritid movement far outweighs the drawbacks of the individual methods because of the need for this information to manage tephritid populations.

The complexities of knowing what it is you are trapping

The effectiveness of any trapping system is highly dependent on the ability to accurately identify the specimens collected. For many fruit fly species, accurate identification (= diagnostics) using morphological or molecular techniques is relatively straightforward and poses few technical challenges. However, nearly all genera of pest tephritids also contain groups of species where single, stand-alone tools are not sufficient for accurate identification: such groups include the Bactrocera dorsalis complex, the Anastrepha fraterculus complex and the Ceratitis FAR complex. Misidentification of high-impact species from such groups can have dramatic consequences and negate the benefits of an otherwise effective trapping program. To help prevent such problems, this chapter defines what is meant by a species complex and describes in detail how the correct identification of species within a complex requires the use of an integrative taxonomic approach. Integrative taxonomy uses multiple, independent lines of evidence to delimit species boundaries, and the underpinnings of this approach from both the theoretical speciation literature and the systematics/taxonomy literature are described. The strength of the integrative approach lies in the explicit testing of hypotheses and the use of multiple, independent species delimitation tools. A case is made for a core set of species delimitation tools (pre- and post-zygotic compatibility tests, multi-locus phylogenetic analysis, chemoecological studies, and morphometric and geometric morphometric analyses) to be adopted as standards by tephritologists aiming to resolve economically important species complexes. In discussing the integrative approach, emphasis is placed on the subtle but important differences between integrative and iterative taxonomy. The chapter finishes with a case study that illustrates how iterative taxonomy applied to the B. dorsalis species complex led to incorrect taxonomic conclusions, which has had major implications for quarantine, trade, and horticultural pest management. In contrast, an integrative approach to the problem has resolved species limits in this taxonomically difficult group, meaning that robust diagnostics are now available.

Seed persistence in the field may be predicted by laboratory-controlled aging

Weed management is complicated by the presence of soil seed banks. The complexity of soil-seed interactions means that seed persistence in the field is often difficult to measure, let alone predict. Field trials, although accurate in their context, are time-consuming and expensive to conduct for individual species. Some ex situ techniques for estimating seed life expectancy have been proposed, but these fail to simulate the environmental complexity of the field. Also, it has been questioned whether techniques such as the controlled aging test (CAT) are useful indicators of field persistence. This study aimed to test the validity of the standard CAT (seed aging at 45 C and 60% relative humidity) in use at the Royal Botanic Gardens, Kew, U.K., for predicting field seed-persistence. Comparison of seed persistence and CAT data for 27 northwest European species suggested a significant positive correlation of 0.31. Subsequently, 13 species of emerging and common weeds of Queensland were assessed for their seed longevity using the CAT. The seed longevity data of these species in the CAT were linked with field seed-persistence data according to three broad seed-persistence categories: <1 yr, 1 to 3 yr, and >3 yr. We discuss the scope for using the CAT as a tool for rapid assignment of species to these categories. There is a need for further studies that compare predictions of seed persistence based on the CAT with seed persistence in the field for a larger range of species and environments.

Recovery of the red-finned blue-eye: An endangered fish from springs of the Great Artesian Basin

The red-finned blue-eye (Scaturiginichthys vermeilipinnis) is endemic to a single complex of springs emanating from the Great Artesian Basin, Australia. The species has been recorded as naturally occurring in eight separate very shallow (generally <20 mm) springs, with a combined wetland area of ~0.3 ha. Since its discovery in 1990, five red-finned blue-eye (RFBE) populations have been lost and subsequent colonisation has occurred in two spring wetlands. Current population size is estimated at <3000 individuals. Artesian bores have reduced aquifer pressure, standing water levels and spring-flows in the district. There is evidence of spatial separation within the spring pools where RFBE and the introduced fish gambusia (Gambusia holbrooki) co-occur, although both species are forced together when seasonal extremes affect spring size and water temperature. Gambusia was present in four of the five springs where RFBE populations have been lost. Four out of the five remaining subpopulations of RFBE are Gambusia free. Circumstantial evidence suggests that gambusia is a major threat to red-finned blue-eyes. The impact of Gambusia is probably exacerbated by domestic stock (cattle and sheep), feral goats and pigs that utilise the springs and can negatively affect water quality and flow patterns. Three attempts to translocate RFBE to apparently suitable springs elsewhere within the complex have failed. Opportunities to mitigate threats are discussed, along with directions for future research to improve management of this extremely threatened fish and habitat.

Weed spread prevention: simple activities for field operations.

This paper discusses how spread of weeds can be minimised by improved knowledge of the weed’s ecology and dispersal, and by better surveillance and treatment methods. Undertaking simple prevention activities reduces the risk of spreading weeds with minimal costs to projects and they noted that field staff and researchers can inadvertently become vectors of weed spread if they do not take adequate precautions. The authors describe several techniques that can be adopted and reference their observations to the eradication program for Siam weed, Chromolaena odorata.

Processes leading to the detection of tropical weed infestations during an eradication program.

The authors identify and track processes that have resulted in the detection of six tropical weeds targeted for eradication. The habitats and distributions of these species make detection by field officers and members of the public more likely than targeted searches. The eradication program is increasing the scope of detection processes by conducting and documenting activities to improve weed recognition amongst public, government and industry stakeholders.