Showing papers by "University of Western Australia published in 2010"

Global threats to human water security and river biodiversity

Abstract: Protecting the world’s freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts for downstream impacts. We find that nearly 80% of the world’s population is exposed to high levels of threat to water security. Massive investment in water technology enables rich nations to offset high stressor levels without remedying their underlying causes, whereas less wealthy nations remain vulnerable. A similar lack of precautionary investment jeopardizes biodiversity, with habitats associated with 65% of continental discharge classified as moderately to highly threatened. The cumulative threat framework offers a tool for prioritizing policy and management responses to this crisis, and underscores the necessity of limiting threats at their source instead of through costly remediation of symptoms in order to assure global water security for both humans and freshwater biodiversity.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

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.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Abstract: We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

International network of cancer genome projects

Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

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.

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

Abstract: 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.

Lipoprotein(a) as a cardiovascular risk factor: current status

Abstract: AIMS: The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies. METHODS AND RESULTS: The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1-3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a). CONCLUSION: We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.

Doctor-patient communication: a review.

Abstract: Effective doctor-patient communication is a central clinical function in building a therapeutic doctor-patient relationship, which is the heart and art of medicine. This is important in the delivery of high-quality health care. Much patient dissatisfaction and many complaints are due to breakdown in the doctor-patient relationship. However, many doctors tend to overestimate their ability in communication. Over the years, much has been published in the literature on this important topic. We review the literature on doctor-patient communication.

Is gold a safe haven? International evidence

Abstract: The aim of this paper is to examine the role of gold in the global financial system. We test the hypothesis that gold represents a safe haven against stocks of major emerging and developing countries. A descriptive and econometric analysis for a sample spanning a 30 year period from 1979 to 2009 shows that gold is both a hedge and a safe haven for major European stock markets and the US but not for Australia, Canada, Japan and large emerging markets such as the BRIC countries. We also distinguish between a weak and strong form of the safe haven and argue that gold may act as a stabilizing force for the financial system by reducing losses in the face of extreme negative market shocks. Looking at specific crisis periods, we find that gold was a strong safe haven for most developed markets during the peak of the recent financial crisis.

THE STRUCTURE AND KINEMATICS OF THE CIRCUMGALACTIC MEDIUM FROM FAR-ULTRAVIOLET SPECTRA OF z ≃ 2-3 GALAXIES*

Abstract: We present new results on the kinematics and spatial distribution of metal-enriched gas within ~125 kpc of star-forming ("Lyman break") galaxies at redshifts 2 ≲ z ≲ 3 In particular, we focus on constraints provided by the rest-frame far-ultraviolet (far-UV) spectra of faint galaxies, and demonstrate how galaxy spectra can be used to obtain key spatial and spectral information more efficiently than possible with QSO sightlines Using a sample of 89 galaxies with z = 23 ± 03 and with both rest-frame far-UV and Hα spectra, we re-calibrate the measurement of accurate galaxy systemic redshifts using only survey-quality rest-UV spectra We use the velocity-calibrated sample to investigate the kinematics of the galaxy-scale outflows via the strong interstellar (IS) absorption lines and Lyα emission (when present), as well as their dependence on other physical properties of the galaxies We construct a sample of 512 close (1"-15") angular pairs of z ~ 2-3 galaxies with redshift differences indicating a lack of physical association Sightlines to the background galaxies provide new information on the spatial distribution of circumgalactic gas surrounding the foreground galaxies The close pairs sample galactocentric impact parameters 3-125 kpc (physical) at = 22, providing for the first time a robust map of cool gas as a function of galactocentric distance for a well-characterized population of galaxies We propose a simple model of circumgalactic gas that simultaneously matches the kinematics, depth, and profile shape of IS absorption and Lyα emission lines, as well as the observed variation of absorption line strength (H I and several metallic species) versus galactocentric impact parameter Within the model, cool gas is distributed symmetrically around every galaxy, accelerating radially outward with v_(out)(r) increasing with r (ie, the highest velocities are located at the largest galactocentric distances r) The inferred radial dependence of the covering fraction of cool gas (which modulates the absorption line strength) is f_c(r) ∝ r^(–γ) with 02 ≲ γ ≲ 06 depending on transition We discuss the results of the observations in the context of "cold accretion," in which cool gas is accreting via filamentary streams directly onto the central regions of galaxies At present, we find little observational evidence for cool infalling material, while evidence supporting the large-scale effects of superwind outflows is strong This "pilot" study using faint galaxy spectra demonstrates the potential of using galaxies to trace baryons within galaxies, in the circumgalactic medium, and ultimately throughout the intergalactic medium

Fluorescence spectroscopy opens new windows into dissolved organic matter dynamics in freshwater ecosystems: A review

Abstract: The biochemical composition of dissolved organic matter (DOM) strongly influences its biogeochemical role in freshwater ecosystems, yet DOM composition measurements are not routinely incorporated into ecological studies. To date, the majority of studies of freshwater ecosystems have relied on bulk analyses of dissolved organic carbon and nitrogen to obtain information about DOM cycling. The problem with this approach is that the biogeochemical significance of DOM can only partially be elucidated using bulk analyses alone because bulk measures cannot detect most carbon and nitrogen transformations. Advances in fluorescence spectroscopy provide an alternative to traditional approaches for characterizing aquatic DOM, and allow for the rapid and precise characterization of DOM necessary to more comprehensively trace DOM dynamics. It is within this context that we discuss the use of fluorescence spectroscopy to provide a novel approach to tackling a longstanding problem: understanding the dynamics and biogeochemical role of DOM. We highlight the utility of fluorescence characterization of DOM and provide examples of the potential range of applications for incorporating DOM fluorescence into ecological studies in the hope that this rapidly evolving technique will further our understanding of the biogeochemical role of DOM in freshwater ecosystems.

Taking Stock: Integrating and Differentiating Multiple Proactive Behaviors

Abstract: The authors aimed to clarify the similarities, differences, and interrelationships among multiple types of proactive behavior. Factor analyses of managers’ self-ratings (N = 622) showed concepts were distinct from each other but related via a higher-order structure. Three higher-order proactive behavior categories were identified—proactive work behavior, proactive strategic behavior, and proactive person-environment fit behavior—each corresponding to behaviors aimed at bringing about change in the internal organization (e.g., voice), the fit between the organization and its environment (e.g., issue selling), and the fit between the individual and the organization (e.g., feedback seeking), respectively. Further analyses on a subsample (n = 319) showed similarities and differences in the antecedents of these behaviors.

Predictions for the rates of compact binary coalescences observable by ground-based gravitational-wave detectors

Abstract: We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Linear Regression for Face Recognition

Abstract: In this paper, we present a novel approach of face identification by formulating the pattern recognition problem in terms of linear regression. Using a fundamental concept that patterns from a single-object class lie on a linear subspace, we develop a linear model representing a probe image as a linear combination of class-specific galleries. The inverse problem is solved using the least-squares method and the decision is ruled in favor of the class with the minimum reconstruction error. The proposed Linear Regression Classification (LRC) algorithm falls in the category of nearest subspace classification. The algorithm is extensively evaluated on several standard databases under a number of exemplary evaluation protocols reported in the face recognition literature. A comparative study with state-of-the-art algorithms clearly reflects the efficacy of the proposed approach. For the problem of contiguous occlusion, we propose a Modular LRC approach, introducing a novel Distance-based Evidence Fusion (DEF) algorithm. The proposed methodology achieves the best results ever reported for the challenging problem of scarf occlusion.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

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.

The generation and evolution of the continental crust

Abstract: The continental crust is the archive of the geological history of the Earth. Only 7% of the crust is older than 2.5 Ga, and yet significantly more crust was generated before 2.5 Ga than subsequently. Zircons offer robust records of the magmatic and crust-forming events preserved in the continental crust. They yield marked peaks of ages of crystallization and of crust formation. The latter might reflect periods of high rates of crust generation, and as such be due to magmatism associated with deep-seated mantle plumes. Alternatively the peaks are artefacts of preservation, they mark the times of supercontinent formation, and magmas generated in some tectonic settings may be preferentially preserved. There is increasing evidence that depletion of the upper mantle was in response to early planetary differentiation events. Arguments in favour of large volumes of continental crust before the end of the Archaean, and the thickness of felsic and mafic crust, therefore rely on thermal models for the progressively cooling Earth. They are consistent with recent estimates that the rates of crust generation and destruction along modern subduction zones are strikingly similar. The implication is that the present volume of continental crust was established 2–3 Ga ago.

The ABC of physical activity for health: A consensus statement from the British Association of Sport and Exercise Sciences

Abstract: Our understanding of the relationship between physical activity and health is constantly evolving. Therefore, the British Association of Sport and Exercise Sciences convened a panel of experts to review the literature and produce guidelines that health professionals might use. In the ABC of Physical Activity for Health, A is for All healthy adults, B is for Beginners, and C is for Conditioned individuals. All healthy adults aged 18-65 years should aim to take part in at least 150 min of moderate-intensity aerobic activity each week, or at least 75 min of vigorous-intensity aerobic activity per week, or equivalent combinations of moderate- and vigorous-intensity activities. Moderate-intensity activities are those in which heart rate and breathing are raised, but it is possible to speak comfortably. Vigorous-intensity activities are those in which heart rate is higher, breathing is heavier, and conversation is harder. Aerobic activities should be undertaken in bouts of at least 10 min and, ideally, should be performed on five or more days a week. All healthy adults should also perform muscle-strengthening activities on two or more days a week. Weight training, circuit classes, yoga, and other muscle-strengthening activities offer additional health benefits and may help older adults to maintain physical independence. Beginners should work steadily towards meeting the physical activity levels recommended for all healthy adults. Even small increases in activity will bring some health benefits in the early stages and it is important to set achievable goals that provide success, build confidence, and increase motivation. For example, a beginner might be asked to walk an extra 10 min every other day for several weeks to slowly reach the recommended levels of activity for all healthy adults. It is also critical that beginners find activities they enjoy and gain support in becoming more active from family and friends. Conditioned individuals who have met the physical activity levels recommended for all healthy adults for at least 6 months may obtain additional health benefits by engaging in 300 min or more of moderate-intensity aerobic activity per week, or 150 min or more of vigorous-intensity aerobic activity each week, or equivalent combinations of moderate- and vigorous-intensity aerobic activities. Adults who find it difficult to maintain a normal weight and adults with increased risk of cardiovascular disease or type 2 diabetes may in particular benefit from going beyond the levels of activity recommended for all healthy adults and gradually progressing towards meeting the recommendations for conditioned individuals. Physical activity is beneficial to health with or without weight loss, but adults who find it difficult to maintain a normal weight should probably be encouraged to reduce energy intake and minimize time spent in sedentary behaviours to prevent further weight gain. Children and young people aged 5-16 years should accumulate at least 60 min of moderate-to-vigorous-intensity aerobic activity per day, including vigorous-intensity aerobic activities that improve bone density and muscle strength.

Evolution of halophytes: multiple origins of salt tolerance in land plants

Abstract: The evolution of salt tolerance is interesting for several reasons. First, since salt-tolerant plants (halophytes) employ several different mechanisms to deal with salt, the evolution of salt tolerance represents a fascinating case study in the evolution of a complex trait. Second, the diversity of mechanisms employed by halophytes, based on processes common to all plants, sheds light on the way that a plant’s physiology can become adapted to deal with extreme conditions. Third, as the amount of salt-affected land increases around the globe, understanding the origins of the diversity of halophytes should provide a basis for the use of novel species in bioremediation and conservation. In this review we pose the question, how many times has salt tolerance evolved since the emergence of the land plants some 450–470 million years ago? We summarise the physiological mechanisms underlying salt-tolerance and provide an overview of the number and diversity of salt-tolerant terrestrial angiosperms (defined as plants that survive to complete their life cycle in at least 200 mM salt). We consider the evolution of halophytes using information from fossils and phylogenies. Finally, we discuss the potential for halophytes to contribute to agriculture and land management and ask why, when there are naturally occurring halophytes, it is proving to be difficult to breed salt-tolerant crops.

Meta-analysis of drug-related deaths soon after release from prison.

Abstract: Aims The transition from prison back into the community is particularly hazardous for drug-using offenders whose tolerance for heroin has been reduced by imprisonment. Studies have indicated an increased risk of drug-related death soon after release from prison, particularly in the first 2 weeks. For precise, up-to-date understanding of these risks, a meta-analysis was conducted on the risk of drug-related death in weeks 1 + 2 and 3 + 4 compared with later 2-week periods in the first 12 weeks after release from prison.Methods English-language studies were identified that followed up adult prisoners for mortality from time of index release for at least 12 weeks. Six studies from six prison systems met the inclusion criteria and relevant data were extracted independently. Results These studies contributed a total of 69 093 person-years and 1033 deaths in the first 12 weeks after release, of which 612 were drug-related. A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3-12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7-9.9); Australia, 4.0 (95% CI: 3.4-4.8); Washing- ton State, USA, 8.4 (95% CI: 5.0-14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3-7.1). Comparing weeks 3 + 4 with weeks 5-12, the pooled relative risk was: 1.7 (95% CI: 1.3-2.2). Conclusions These findings confirm that there is an increased risk of drug-related death during the first 2 weeks after release from prison and that the risk remains elevated up to at least the fourth week.

Genome-wide association study identifies five loci associated with lung function.

Abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Information from Pharmaceutical Companies and the Quality, Quantity, and Cost of Physicians' Prescribing: A Systematic Review

Abstract: Background Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing.

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Abstract: To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.

DUST OBSCURATION AND METALLICITY AT HIGH REDSHIFT: NEW INFERENCES FROM UV, Hα, AND 8 μm OBSERVATIONS OF z ∼ 2 STAR-FORMING GALAXIES*

Abstract: We use a sample of 90 spectroscopically confirmed Lyman break galaxies with Hα measurements and Spitzer MIPS 24 μm observations to constrain the relationship between rest-frame 8 μm luminosity (L_8) and star formation rate (SFR) for L* galaxies at z ~ 2. We find a tight correlation with 0.24 dex scatter between L_8 and Hα luminosity/SFR for z ~ 2 galaxies with 10^(10) L_☉ ≲ L_(IR) ≲ 10^(12) L_☉. Employing this relationship with a larger sample of 392 galaxies with spectroscopic redshifts, we find that the UV slope β can be used to recover the dust attenuation of the vast majority of moderately luminous L* galaxies at z ~ 2 to within a 0.4 dex scatter using the local correlation. Separately, young galaxies with ages ≲100 Myr appear to be less dusty than their UV slopes would imply based on the local trend and may follow an extinction curve that is steeper than what is typically assumed. Consequently, very young galaxies at high redshift may be significantly less dusty than inferred previously. Our results provide the first direct evidence, independent of the UV slope, for a correlation between UV and bolometric luminosity (L_(bol)) at high redshift, in the sense that UV-faint galaxies are on average less infrared and less bolometrically luminous than their UV-bright counterparts. The L_(bol)-L_(UV) relation indicates that as the SFR increases, L_(UV) turns over (or "saturates") around the value of L* at z ~ 2, implying that dust obscuration may be largely responsible for modulating the bright end of the UV luminosity function. Finally, dust attenuation is found to correlate with oxygen abundance at z ~ 2. Accounting for systematic differences in local and high-redshift metallicity calibrations, we find that L* galaxies at z ~ 2, while at least an order of magnitude more bolometrically luminous, exhibit ratios of metals to dust that are similar to those of local starbursts. This result is expected if high-redshift galaxies are forming their stars in a less metal-rich environment compared to local galaxies of the same luminosity, thus naturally leading to a redshift evolution in both the bolometric luminosity-metallicity and bolometric luminosity-obscuration relations.

Iron Oxide Copper-Gold (IOCG) Deposits through Earth History: Implications for Origin, Lithospheric Setting, and Distinction from Other Epigenetic Iron Oxide Deposits

Abstract: The iron oxide copper-gold (IOCG) group of deposits, initially defined following discovery of the giant Olympic Dam Cu-U-Au deposit, has progressively become too-embracing when associated deposits and potential end members or analogs are included. The broader group includes several low Ti iron oxide-associated deposits that include iron oxide (P-rich), iron oxide (F- and REE-rich), Fe or Cu-Au skarn, high-grade iron oxide-hosted Au ± Cu, carbonatite-hosted (Cu-, REE-, and F-rich), and IOCG sensu stricto deposits. Consideration of this broad group as a whole obscures the critical features of the IOCG sensu stricto deposits, such as their temporal distribution and tectonic environment, thus leading to difficulties in developing a robust exploration model. The IOCG sensu stricto deposits are magmatic-hydrothermal deposits that contain economic Cu and Au grades, are structurally controlled, commonly contain significant volumes of breccia, are commonly associated with presulfide sodic or sodic-calcic alteration, have alteration and/or brecciation zones on a large, commonly regional, scale relative to economic mineralization, have abundant low Ti iron oxides and/or iron silicates intimately associated with, but generally paragenetically older than, Fe-Cu sulfides, have LREE enrichment and low S sulfides (lack of abundant pyrite), lack widespread quartz veins or silicification, and show a clear temporal, but not close spatial, relationship to major magmatic intrusions. These intrusions, where identified, are commonly alkaline to subalkaline, mixed mafic (even ultramafic) to felsic in composition, with evidence for mantle derivation of at least the mafic end members of the suite. The giant size of many of the deposits and surrounding alteration zones, the highly saline ore fluids, and the available stable and radiogenic isotope data indicate release of deep, volatile-rich magmatic fluids through devolatization of causative, mantle-derived magmas and variable degrees of mixing of these magmatic fluids with other crustal fluids along regional-scale fluid flow paths. Precambrian deposits are the dominant members of the IOCG group in terms of both copper and gold resources. The 12 IOCG deposits with >100 tonnes (t) resources are located in intracratonic settings within about 100 km of the margins of Archean or Paleoproterozoic cratons or other lithospheric boundaries, and formed 100 to 200 m.y. after supercontinent assembly. Their tectonic setting at formation was most likely anorogenic, with magmatism and associated hydrothermal activity driven by mantle underplating and/or plumes. Limited amounts of partial melting of volatile-rich and possibly metal-enriched metasomatized early Precambrian subcontinental lithospheric mantle (SCLM), fertilized during earlier subduction, probably produced basic to ultrabasic magmas that melted overlying continental crust and mixed with resultant felsic melts, with devolatilization and some penecontemporaneous incorporation of other lower to middle crustal fluids to produce the IOCG deposits. Preservation of near-surface deposits, such as Olympic Dam, is probably due to their formation above buoyant and refractory SCLM, which resisted delamination and associated uplift. Most Precambrian iron oxide (P-rich) or magnetite-apatite (Kiruna-type) deposits have a different temporal distribution, apparently forming in convergent margin settings prior to or following supercontinent assembly. It is only in the Phanerozoic that IOCG and magnetite-apatite deposits are roughly penecontemporaneous in convergent margin settings. The Phanerozoic IOCG deposits, such as Candelaria, Chile, occur in anomalous extensional to transtensional zones in the Coastal Cordillera, which are also the sites of mantle-derived mafic to felsic intrusions that are anomalous in an Andean context. This implies that special conditions, possibly detached slabs of metasomatized SCLM, may be required in convergent margin settings to generate world-class IOCG deposits. It is likely that formation of giant IOCG deposits was mainly a Precambrian phenomenon related to the extensive mantle underplating that impacted on buoyant metasomatized SCLM. Generally smaller and rarer Phanerozoic IOCG deposits formed in tectonic settings where conditions similar to those in the Precambrian were replicated.