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The mid-infrared transmission spectra of Antarctic ureilites.

The mid-infrared (4000-450 cm-1; 2.5-22.2 micrometers) transmission spectra of seven Antarctic ureilites and 10 Antarctic H-5 ordinary chondrites are presented. The ureilite spectra show a number of absorption bands, the strongest of which is a wide, complex feature centered near 1000 cm-1 (10 micrometers) due to Si-O stretching vibrations in silicates. The profiles and positions of the substructure in this feature indicate that Mg-rich olivines and pyroxenes are the main silicates responsible. The relative abundances of these two minerals, as inferred from the spectra, show substantial variation from meteorite to meteorite, but generally indicate olivine is the most abundant (olivine:pyroxene = 60:40 to 95:5). Both the predominance of olivine and the variable olivine-to-pyroxene ratio are consistent with the known composition and heterogeneity of ureilites. The H-5 ordinary chondrites spanned a range of weathering classes and were used to provide a means of addressing the extent to which the ureilite spectra may have been altered by weathering processes. It was found that, while weathering of these meteorites produces some weak bands due to the formation of small amounts of carbonates and hydrates, the profile of the main silicate feature has been little affected by Antarctic exposure in the meteorites studied here. The mid-infrared ureilite spectra provide an additional means of testing potential asteroidal parent bodies for the ureilites. At present, the best candidates include the subset of S-type asteroids having low albedos and weak absorption features in the near infrared.

Antarctic Regions↗

The Phanerozoic record of global sea-level change.

We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 +/- 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 10(4)- to 10(6)-year scale, but a link between oxygen isotope and sea level on the 10(7)-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present).

Journal Article↗

Continuous tracking of the Australian National Tobacco Campaign: advertising effects on recall, recognition, cognitions, and behaviour.

OBJECTIVES: To relate Australian National Tobacco Campaign advertising to outcome measures such as smokers' awareness of and reaction to the campaign, and indicators of interest in smoking cessation. DESIGN: Continuous tracking was used to survey random cross sectional samples of the target audience via telephone interviews. Baseline measures were collected preceding each advertising phase, whereafter subjects were interviewed on a weekly basis for the entire period of each phase. Changes in outcomes could thus be inferred on a weekly basis allowing variations in advertising intensity to be monitored for effect. Three phases were evaluated variously in Melbourne, Sydney, and Adelaide. SUBJECTS: A total of 9033 subjects aged 18-40 years were interviewed. Age and sex of the sample were evenly distributed. RESULTS: In general, it was found that the greater the media weight, the greater the recall and recognition mediated by the message of the advertisement and the creative execution-advertisements with a clear figure ground executional format appeared more memorable than those without, and health effects advertisements were more memorable than those encouraging calls to a quitline. The relationship between various communication effects and media weight was limited by the confounding of prior activities in two of the phases. CONCLUSIONS: Advertisements with clear figure ground executional formats and those illustrating health effects of smoking have high memorability. Future campaigns that are continuously tracked are recommended to systematically vary media weight, flighting schedules, and advertisement type, so as to maximise information about these variables and their interactions.

Adolescent↗

Adjusting craniofacial correlations for technical error.

Reliability estimates provide a means of adjusting observed correlations for technical error. The results show that the true correlations among 11 craniofacial landmarks are consistently higher than observed values. Consequently, the regression slopes defining these relationships are also increased. The less reliable two measures are, and the closer their joint reliability approximates the observed correlation, the greater the expected change in true correlation. Adjusting craniofacial relationships for technical error may substantially increase the proportion of variation explained, and thereby alter statistical inferences drawn from results.

Cephalometry↗

An initial survey for Wolbachia (Rickettsiales: Rickettsiaceae) infections in selected California mosquitoes (Diptera: Culicidae).

Knowledge of biogeographic variation in Wolbachia infection rates and inferred susceptibility to infection among different mosquito taxa has fundamental implications for the design and successful application of Wolbachia-based vector-borne disease control strategies. Using a Wolbachia-specific polymerase chain reaction assay, we tested 14 North American mosquito species in five genera (Aedes, Anopheles, Culiseta, Culex, and Ochlerotatus) for Wolbachia infection. Wolbachia infections were only detected in members of the Culex pipiens (L.) species complex.

Animals↗

[How does model- and situation-specific lack of knowledge affect causal inferences?].

A model proposed by Thüring (1991) for inferences based on causal knowledge was empirically tested. According to this model, two variables affect the certainty with which a causal inference is concluded: insufficiency (model-specific uncertainty) and ambiguity (situation-specific uncertainty). Within an experiment these two variables were manipulated. Both had a very significant (p < .01) influence on causal inferences. In respect to its quantity, variation of ambiguity had the effect predicted in the model. Concerning insufficiency, distinct differences between predicted and empirical ratings were found. Reasons for these deviations and model modifications resulting therefrom are discussed.

Adult↗

The healthcare cost and utilization project: an overview.

DATABASE: . Healthcare Cost and Utilization Project (HCUP)-a family of databases including the State Inpatient Databases (SID), the Nationwide Inpatient Sample (NIS), the Kids' Inpatient Database (KID), and the outpatient databases State Ambulatory Surgery Data (SASD) and State Emergency Department Data (SEDD). DESCRIPTION: Multistate, inpatient (SID, NIS, KID) and outpatient (SASD, SEDD) discharge records on insured and uninsured patients. SOURCE: Partnership between the Agency for Healthcare Research and Quality (AHRQ) and public and private statewide data organizations. AVAILABLE DATA: Selected data elements from inpatient and outpatient discharge records, including patient demographic, clinical, disposition and diagnostic/procedural information; hospital identification (ID); facility charges; and other facility information. DATA YEARS AVAILABLE: Varies by database: NIS 1988-2000; SID 1995-2000; KID 1997 and 2000; SASD 1995-2000; and SEDD in pilot phase. Future data years anticipated for all datasets and back years for SID and SASD. UNITS OF ANALYSIS: Patient (in states with encrypted patient identification), physician, market, and state. RESEARCH QUESTIONS: Quality assessment, use and cost of hospital services, medical treatment variations, use of ambulatory surgery services, diffusion of medical technology, impact of health policy changes, access to care (inference), study of rare illness or procedures, small area variations, and care of special populations. STRENGTHS: Largest collection of all-payer, uniform, state-based inpatient and ambulatory surgery administrative data. LIMITATIONS: Lacks clinical detail (e.g., stage of disease, vital statistics) and laboratory and pharmacy data. Ability to track patients across time and setting varies by state. ACCESS TO DATA: Access available to all users who sign and abide by the Data Use Agreement. Application kits available at www.ahrq.gov/data/hcup. HCUPnet, an on-line interactive query tool, allows access to data without purchase (www.ahrq. gov/data/hcup/hcupnet.htm).

Ambulatory Care↗

Processor quality assurance using digital imaging.

The purpose of this study was to develop and test a computer imaging method for assessing longitudinal processor variability. A technique called adaptive histogram equalization was used to test deviation in automatic processing when a test film is compared with a time-temperature processed standard at two different kVp's and film speeds. In a 14-day study we found that the density ranges for the standard film did not change, while the density range of the automatically processed films changed by a factor of two. These results suggest that if automatic processing is to be used for films taken as part of a longitudinal study-for example, subtraction-then processor variation can potentially lead to incorrect inference of bone gain or loss.

Absorptiometry, Photon↗

Genetic isolation by distance in Arabidopsis thaliana: biogeography and postglacial colonization of Europe.

Arabidopsis thaliana provides a useful model system for functional, evolutionary and ecological studies in plant biology. We have analysed natural genetic variation in A. thaliana in order to infer its biogeographical and historical distribution across Eurasia. We analysed 79 amplified fragment length polymorphism (AFLP) markers in 142 accessions from the species' native range, and found highly significant genetic isolation by distance among A. thaliana accessions from Eurasia and southern Europe. These spatial patterns of genetic variation suggest that A. thaliana colonized central and northern Europe from Asia and from Mediterranean Pleistocene refugia, a trend which has been identified in other species. Statistically significant levels of multilocus linkage disequilibrium suggest intermediate levels of disequilibrium among subsets of loci, and analysis of genetic relationships among accessions reveal a star or bush-like dendrogram with low bootstrap support. Taken together, it appears that there has been sufficient historical recombination in the A. thaliana genome such that accessions do not conform to a tree-like, bifurcating pattern of evolution - there is no 'ecotype phylogeny.' Nonetheless, significant isolation by distance provides a framework upon which studies of natural variation in A. thaliana may be designed and interpreted.

Arabidopsis↗

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have largely been understudied in medical research due to their complex genetic ancestries. However, the consideration of admixture can help identify ancestry-enriched genetic associations, delineating some of the genetic underpinnings of cross-population phenotypic variation. To this end, we performed local ancestry inference within the All of Us Research Program to identify individuals with recent admixture between African (AFR) and European (EUR) populations (N=48,921). We identified evidence of local AFR ancestry enrichment at the HLA locus, suggestive of putative selection since admixture. Furthermore, we performed the largest admixture mapping (ADM) efforts in AFR-EUR Admixed individuals for 22 traits, identifying 71 associations between inferred local AFR ancestries and a trait. Variants from published GWAS could only account for 18 (25%) of the ADM associations, highlighting novel loci where ancestral haplotypes explained some phenotypic variation. Previous studies likely have not identified these loci due to the low availability of high-powered GWAS in populations genetically similar to AFR. One such loci was 9q21.33, associated with 1.4-fold risk of end-stage kidney disease (ESKD) for carriers of inferred local AFR ancestries at the region. This locus contains the gene SLC28A3, which has previously been linked to kidney function but has never been associated with cross-population ESKD prevalence differences. Together, our results expand upon the existing literature on phenotypic differences between populations, highlighting loci where genetic ancestries play a critical role in the genetic architecture of disease.

Journal Article↗

A comprehensive model of mutations affecting fitness and inferences for Arabidopsis thaliana.

As the ultimate source of genetic variation, spontaneous mutation is essential to evolutionary change. Theoretical studies over several decades have revealed the dependence of evolutionary consequences of mutation on specific mutational properties, including genomic mutation rates, U, and the effects of newly arising mutations on individual fitness, s. The recent resurgence of empirical effort to infer these properties for diverse organisms has not achieved consensus. Estimates, which have been obtained by methods that assume mutations are unidirectional in their effects on fitness, are imprecise. Both because a general approach must allow for occurrence of fitness-enhancing mutations, even if these are rare, and because recent evidence demands it, we present a new method for inferring mutational parameters. For the distribution of mutational effects, we retain Keightley's assumption of the gamma distribution, to take advantage of the flexibility of its shape. Because the conventional gamma is one sided, restricting it to unidirectional effects, we include an additional parameter, rho, as an amount it is displaced from zero. Estimation is accomplished by Markov chain Monte Carlo maximum likelihood. Through a limited set of simulations, we verify the accuracy of this approach. We apply it to analyze data on two reproductive fitness components from a 17-generation mutation-accumulation study of a Columbia accession of Arabidopsis thaliana in which 40 lines sampled in three generations were assayed simultaneously. For these traits, U approximately/= 0.1-0.2, with distributions of mutational effects broadly spanning zero, such that roughly half the mutations reduce reproductive fitness. One evolutionary consequence of these results is lower extinction risks of small populations of A. thaliana than expected from the process of mutational meltdown. A comprehensive view of the evolutionary consequences of mutation will depend on quantitatively accounting for fitness-enhancing, as well as fitness-reducing, mutations.

Algorithms↗

Re-interpreting conventional interval estimates taking into account bias and extra-variation.

BACKGROUND: The study design with the smallest bias for causal inference is a perfect randomized clinical trial. Since this design is often not feasible in epidemiologic studies, an important challenge is to model bias properly and take random and systematic variation properly into account. A value for a target parameter might be said to be "incompatible" with the data (under the model used) if the parameter's confidence interval excludes it. However, this "incompatibility" may be due to bias and/or extra-variation. DISCUSSION: We propose the following way of re-interpreting conventional results. Given a specified focal value for a target parameter (typically the null value, but possibly a non-null value like that representing a twofold risk), the difference between the focal value and the nearest boundary of the confidence interval for the parameter is calculated. This represents the maximum correction of the interval boundary, for bias and extra-variation, that would still leave the focal value outside the interval, so that the focal value remained "incompatible" with the data. We describe a short example application concerning a meta analysis of air versus pure oxygen resuscitation treatment in newborn infants. Some general guidelines are provided for how to assess the probability that the appropriate correction for a particular study would be greater than this maximum (e.g. using knowledge of the general effects of bias and extra-variation from published bias-adjusted results). SUMMARY: Although this approach does not yet provide a method, because the latter probability can not be objectively assessed, this paper aims to stimulate the re-interpretation of conventional confidence intervals, and more and better studies of the effects of different biases.

Bias↗

Species-wide gene editing of a flowering regulator reveals hidden phenotypic variation.

Genes do not act in isolation, and the effects of a specific variant at one locus can often be greatly modified by polymorphic variants at other loci. A good example is FLOWERING LOCUS C (FLC), which has been inferred to explain much of the flowering time variation in Arabidopsis thaliana. We use a set of 62 flc species-wide mutants to document pleiotropic, genotype-dependent effects for FLC on flowering as well as several other traits. Time to flowering was greatly reduced in all mutants, with the remaining variation explained mainly by allelic variation at the FLC target FT. Analysis of FT sequence variation suggested that extremely early combinations of FLC and FT alleles should exist in the wild, which we confirmed by targeted collections. Our study provides a proof of concept on how pan-genetic analysis of hub genes can reveal the true extent of genetic networks in a species.

Gene Editing↗

A comprehensive study of genic variation in natural populations of Drosophila melanogaster. IV. Mitochondrial DNA variation and the role of history vs. selection in the genetic structure of geographic populations.

Preliminary studies with restriction fragment length polymorphisms of mitochondrial DNA (mtDNA) in natural populations of Drosophila melanogaster revealed considerable variation in terms of nucleotide sequence and overall size. In this report we present data from more isofemale lines and more restriction enzymes, and explore the utility of the data in inferring a colonization history of this species. Size variation in the noncoding A + T-rich region is particularly plentiful, with size variants occurring in all restriction site haplotypes in all populations. We report here classes of small-scale mobility polymorphisms (apparent range of 20 bp) in specific restriction fragments in the coding region. The variation in one such fragment appears to be generated even more rapidly than in the noncoding region. On the basis of the distribution of restriction site haplotypes, the species range can be divided into three major regions along longitudinal lines: Euro-African populations are the most diverse and are taken to be oldest; Far East populations have a complex distribution of haplotypes; Western Hemisphere populations are the least diverse and are interpreted to be the youngest. The history inferred from mtDNA alone is remarkably similar to one based on several nuclear markers. The mtDNA haplotype distribution is also very different from that of allozymes in these same populations. We interpret this as further evidence that natural selection is still the most parsimonious explanation for the parallel latitudinal allozyme clines in this species.

Animals↗

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N&#x2009;=&#x2009;48,921). Across 22 traits, we identified 71 ancestry-trait associations, including loci where ancestral haplotypes explained phenotypic variation yet were missed by single-variant association testing due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries are associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in explaining differences between populations. Together, our results expand upon the phenotypic differences between populations and characterize loci where genetic ancestries play a critical role in the architecture of disease.

Humans↗

Geological barriers and restricted gene flow in the holarctic skipper Hesperia comma (Hesperiidae).

Patterns of genetic variation within a species may be a consequence of historical factors, such as past fragmentation, as well as current barriers to gene flow. Using sequence data from the mitochondrial cytochrome oxidase subunit II region (COII) and the nuclear gene wingless, we conducted a phylogeographical study of the holarctic skipper Hesperia comma to elucidate patterns of genetic diversity and to infer historical and contemporary processes maintaining genetic variation. One hundred and fifty-one individuals were sampled from throughout North America and Eurasia, focusing on California and adjacent regions in the western United States where morphological diversity is highest compared to the rest of the range. Analyses of sequence data obtained from both genes revealed a well-supported division between the Old and New World. Within western North America, wingless shows little geographical structure, while a hierarchical analysis of genetic diversity of COII sequences indicates three major clades: a western clade in Oregon and Northern California, an eastern clade including the Great Basin, Rocky Mountains and British Columbia, and a third clade in southern California. The Sierra Nevada and the Transverse Ranges appear to be the major barriers to gene flow for H. comma in the western United States. Relatively reduced haplotype diversity in Eurasia compared to North America suggests that populations on the two continents have been affected by different historical processes.

Animals↗

Cryptic species of rockfishes (Sebastes: Scorpaenidae) in the southern hemisphere inferred from mitochondrial lineages.

We used mitochondrial DNA sequence variation of Sebastes from the southeastern Pacific and three localities in the South Atlantic to address long-standing systematic and evolutionary issues regarding the number of species in the Southern Hemisphere. Sequences of the hypervariable mitochondrial control region were obtained from 10 specimens of S. capensis from South Africa (n = 5) and from Tristan da Cunha Island (n = 5) and 27 of S. oculatus from Valparaiso, Chile (n = 10), and the Falkland Islands (n = 17). Results of the study include (1) significant levels of genetic differentiation among the sampled populations (phi ST = 0.225, P < .000001), thus indicating limited gene flow; (2) corroboration of the existence of two different lineages of austral Sebastes corresponding to S. capensis and S. oculatus; (3) finding that S. capensis is not restricted to Tristan da Cunha and South Africa, but is widespread across the South Atlantic; (4) the position of S. capensis as the ancestral lineage of the austral Sebastes; (5) the existence of a third evolutionary lineage with high levels of genetic divergence, particularly abundant in the south-western Atlantic, which may be recognized as a third austral species of Sebastes.

Animals↗

Statistical properties of the variation at linked microsatellite loci: implications for the history of human Y chromosomes.

It has recently been suggested that observed levels of variation at microsatellite loci can be used to infer patterns of selection in genomes and to assess demographic history. In order to evaluate the feasibility of these suggestions it is necessary to know something about how levels of variation at microsatellite loci are expected to fluctuate due simply to stochasticity in the processes of mutation and inheritance (genetic sampling). Here we use recently derived properties of the stepwise mutation model to place confidence intervals around the variance in repeat score that is expected at mutation-drift equilibrium and outline a statistical test for whether an observed value differs significantly from expectation. We also develop confidence intervals for the time course of the buildup of variation following a complete elimination of variation, such as might be caused by a selective sweep or an extreme population bottleneck. We apply these methods to the variation observed at human Y-specific microsatellites. Although a number of authors have suggested the possibility of a very recent sweep, our analyses suggest that a sweep or extreme bottleneck is unlikely to have occurred anytime during the last approximately 74,000 years. To generate this result we use a recently estimated mutation rate for microsatellite loci of 5.6 x 10(-4) along with the variation observed at autosomal microsatellite loci to estimate the human effective population size. This estimate is 18,000, implying an effective number of 4,500 Y chromosomes. One important general conclusion to emerge from this study is that in order to reject mutation-drift equilibrium at a set of linked microsatellite loci it is necessary to have an unreasonably large number of loci unless the observed variance is far below that expected at mutation-drift equilibrium.

Biological Evolution↗