bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Strain‐Specific and Overall Efficacy of Polyvalent Vaccines Against Recurrent Pathogens From a Cross‐Sectional Study
Authors: Auranen Kari , Rinta‐Kokko Hanna , Halloran M. Elizabeth 
Published: February 2013

SummaryEvaluating vaccine efficacy for protection against colonization with bacterial pathogens is an area of growing interest. Colonization of the nasopharynx is an asymptomatic carrier state responsible for person‐to‐person transmission. It differs from most clinical outcomes in that it is common, recurrent, and observed only in its prevalent state. To estimate rates of acquisition and clearance of colonization requires repeated active sampling of the same individuals over time, an expensive and invasive undertaking. Motivated by feasibility constraints in efficacy trials with colonization endpoints, investigators have been estimating vaccine efficacy from cross‐sectional studies without principled methods. We present two examples of vaccine studies estimating vaccine efficacy from cross‐sectional data on nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus). This study presents a framework for defining and estimating strain‐specific and overall vaccine efficacy for susceptibility to acquisition of colonization () when there is a large number of strains with mutual interactions and recurrent dynamics of colonization. We develop estimators based on one observation of the current status per study subject, evaluate their robustness, and re‐analyze the two vaccine trials. Methodologically, the proposed estimators are closely related to case–control studies with prevalent cases, with appropriate consideration of the at‐risk time in choosing the controls.
An Application of Targeted Maximum Likelihood Estimation to the Meta‐Analysis of Safety Data
Authors: Gruber Susan , van der Laan Mark J. 
Published: February 2013

SummarySafety analysis to estimate the effect of a treatment on an adverse event poses a challenging statistical problem even in randomized controlled trials because these events are typically rare, so studies originally powered for efficacy are underpowered for safety outcomes. A meta‐analysis of data pooled across multiple studies may increase power, but missingness in the outcome or failed randomization can introduce bias. This article illustrates how targeted maximum likelihood estimation (TMLE) can be applied in a meta‐analysis to reduce bias in causal effect estimates, and compares performance with other estimators in the literature. A simulation study in which missingness in the outcome is at random or completely at random highlights the differences in estimators with respect to the potential gains in bias and efficiency. Risk difference, relative risk, and odds ratio of the effect of treatment on 30‐daymortality are estimated from data from eight randomized controlled trials. When an outcome event is rare there may be little opportunity to improve efficiency, and associations between covariates and the outcome may be hard to detect. TMLE attempts to exploit the available information to either meet or exceed the performance of a less sophisticated estimator.
Hierarchical Factor Models for Large Spatially Misaligned Data: A Low‐Rank Predictive Process Approach
Authors: Ren Qian , Banerjee Sudipto 
Published: February 2013

SummaryThis article deals with jointly modeling a large number of geographically referenced outcomes observed over a very large number of locations. We seek to capture associations among the variables as well as the strength of spatial association for each variable. In addition, we reckon with the common setting where not all the variables have been observed over all locations, which leads to spatial misalignment. Dimension reduction is needed in two aspects: (i) the length of the vector of outcomes, and (ii) the very large number of spatial locations. Latent variable (factor) models are usually used to address the former, although low‐rank spatial processes offer a rich and flexible modeling option for dealing with a large number of locations. We merge these two ideas to propose a class of hierarchical low‐rank spatial factor models. Our framework pursues stochastic selection of the latent factors without resorting to complex computational strategies (such as reversible jump algorithms) by utilizing certain identifiability characterizations for the spatial factor model. A Markov chain Monte Carlo algorithm is developed for estimation that also deals with the spatial misalignment problem. We recover the full posterior distribution of the missing values (along with model parameters) in a Bayesian predictive framework. Various additional modeling and implementation issues are discussed as well. We illustrate our methodology with simulation experiments and an environmental data set involving air pollutants in California.
The senior discount: biases against older career changers
Authors: Fritzsche Barbara , Marcus Justin 
Published: February 2013

AbstractThis study examined age discrimination in between‐ vs. within‐career job transitions. We expected that older workers transitioning into a new field would experience greater age discrimination than those who change jobs within the same field, particularly when amount of prior job experience is not made salient, and particularly when decision‐makers were highly prejudiced. Results suggested that younger job applicants received higher suitability ratings than older job applicants, and job applicants making a within‐career transition were rated higher than those making a between‐career transition. As hypothesized, older job applicants making between‐career transitions would receive the lowest ratings of suitability for hire when no information regarding experience was presented, and when decision‐makers were highly prejudiced. Implications for the aging workforce are discussed.
Palatal rugae and their role in forensic odontology
Authors: Jain Anoop , Chowdhary Ramesh 
Published: February 2013

AbstractEstablishing a person's identity can be a difficult task in cases of traffic accidents or in mass disaster situations. The records collected to identify a decedent should be accurate and totally inclusive of objective findings. When a victim has no teeth, information for use in personal identification based on methods available in forensic odontology is much more limited than in the case of dentate victims. Palatal rugae have been considered relevant for human identification due to its stability, which is equivalent to the fingerprint, in that it is unique for each ruga pattern. Palatal rugae appear to possess the features of an ideal forensic identification parameter, that is, uniqueness, postmortem resistance, and stability. The purpose of this article was to review the literature, in order to determine if there is enough evidence to establish the use of palatal rugae in dental identification.
Measuring inbreeding and inbreeding depression on pig growth from pedigree or SNP‐derived metrics
Authors: Silió L. , Rodríguez M.C. , Fernández A. , Barragán C. , Benítez R. , Óvilo C. , Fernández A.I. 
Published: February 2013

SummaryMultilocus homozygosity, measured as the proportion of the autosomal genome in homozygous genotypes or in runs of homozygosity, was compared with the respective pedigree inbreeding coefficients in 64 Iberian pigs genotyped using the Porcine SNP60 Beadchip. Pigs were sampled from a set of experimental animals with a large inbreeding variation born in a closed strain with a completely recorded multi‐generation genealogy. Individual inbreeding coefficients calculated from pedigree were strongly correlated with the different SNP‐derived metrics of homozygosity (r = 0.814–0.919). However, unequal correlations between molecular and pedigree inbreeding were observed at chromosomal level being mainly dependent on the number of SNPs and on the correlation between heterozygosities measured across different loci. A panel of 192 SNPs of intermediate frequencies was selected for genotyping 322 piglets to test inbreeding depression on postweaning growth performance (daily gain and weight at 90 days). The negative effects on these traits of homozygosities calculated from the genotypes of 168 quality‐checked SNPs were similar to those of inbreeding coefficients. The results support that few hundreds of SNPs may be useful for measuring inbreeding and inbreeding depression, when the population structure or the mating system causes a large variance of inbreeding.
Discovering medical conditions associated with periodontitis using linked electronic health records
Authors: Boland Mary Regina , Hripcsak George , Albers David J. , Wei Ying , Wilcox Adam B. , Wei Jin , Li Jianhua , Lin Steven , Breene Michael , Myers Ronnie , Zimmerman John , Papapanou Panos N. , Weng Chunhua 
Published: February 2013

AbstractAimTo use linked electronic medical and dental records to discover associations between periodontitis and medical conditions independent of a priori hypotheses.Materials and MethodsThis case‐control study included 2475 patients who underwent dental treatment at the College of Dental Medicine at Columbia University and medical treatment at NewYork‐Presbyterian Hospital. Our cases are patients who received periodontal treatment and our controls are patients who received dental maintenance but no periodontal treatment. Chi‐square analysis was performed for medical treatment codes and logistic regression was used to adjust for confounders.ResultsOur method replicated several important periodontitis associations in a largely Hispanic population, including diabetes mellitus type I (OR = 1.6, 95% CI 1.30–1.99, p < 0.001) and type II (OR = 1.4, 95% CI 1.22–1.67, p < 0.001), hypertension (OR = 1.2, 95% CI 1.10–1.37, p < 0.001), hypercholesterolaemia (OR = 1.2, 95% CI 1.07–1.38, p = 0.004), hyperlipidaemia (OR = 1.2, 95% CI 1.06–1.43, p = 0.008) and conditions pertaining to pregnancy and childbirth (OR = 2.9, 95% CI: 1.32–7.21, p = 0.014). We also found a previously unreported association with benign prostatic hyperplasia (OR = 1.5, 95% CI 1.05–2.10, p = 0.026) after adjusting for age, gender, ethnicity, hypertension, diabetes, obesity, lipid and circulatory system conditions, alcohol and tobacco abuse.ConclusionsThis study contributes a high‐throughput method for associating periodontitis with systemic diseases using linked electronic records.
Effect of Age on Treatment Outcomes in Clostridium difficile Infection
Authors: Louie Thomas J. , Miller Mark A. , Crook Derrick W. , Lentnek Arnold , Bernard Louis , High Kevin P. , Shue Youe‐Kong , Gorbach Sherwood L. 
Published: February 2013

ObjectivesTo determine the effect of advancing age on the clinical outcomes of Clostridium difficile (CDI) treatment.DesignRegression modeling of results from two double‐blind randomized multicenter studies on the treatment of primary and first recurrent cases of CDI to examine for effects of age and study drug on outcomes of cure (resolution of diarrhea), recurrence within 4 weeks of completing successful therapy, and cure without recurrence.SettingParticipants were randomized into studies in the United States, Canada, and Europe.ParticipantsNine hundred ninety‐nine individuals with toxin‐positive CDI were randomized to receive vancomycin (125 mg 4 times daily) or fidaxomicin (200 mg twice daily) for 10 days.MeasurementsThe effect of advancing age in those aged 18 to 40 years and in 10‐year increments thereafter was examined.ResultsThe model predicts a 17% lower clinical cure, 17% greater recurrence, and 13% lower sustained clinical response by advancing decade than in those younger than 40 (P < .01 each). Clinical cure was similar in the fidaxomicin and vancomycin treatment groups, although fidaxomicin was associated with a more than 50% lower relative risk for recurrence than vancomycin (P < .001). Multivariate regression modeling showed that risk factors accounting for poorer outcomes with advancing age include infection with the BI strain type, inpatient status, renal insufficiency, leukocytosis, hypoalbuminemia, and concomitant medication exposure.ConclusionMeasurable and progressive deterioration in CDI treatment outcomes occurred with advancing age in those aged 40 and older, highlighting the need for prevention and treatment strategies. Fidaxomicin treatment was associated with a 60% lower risk of recurrence than vancomycin after adjusting for age, concomitant antibiotics, and C. difficile strain.
Analytical Propagation of Uncertainty in Life Cycle Assessment Using Matrix Formulation
Authors: Imbeault‐Tétreault Hugues , Jolliet Olivier , Deschênes Louise , Rosenbaum Ralph K. 
Published: February 2013

SummaryInventory data and characterization factors in life cycle assessment (LCA) contain considerable uncertainty. The most common method of parameter uncertainty propagation to the impact scores is Monte Carlo simulation, which remains a resource‐intensive option—probably one of the reasons why uncertainty assessment is not a regular step in LCA. An analytical approach based on Taylor series expansion constitutes an effective means to overcome the drawbacks of the Monte Carlo method. This project aimed to test the approach on a real case study, and the resulting analytical uncertainty was compared with Monte Carlo results. The sensitivity and contribution of input parameters to output uncertainty were also analytically calculated. This article outlines an uncertainty analysis of the comparison between two case study scenarios. We conclude that the analytical method provides a good approximation of the output uncertainty. Moreover, the sensitivity analysis reveals that the uncertainty of the most sensitive input parameters was not initially considered in the case study. The uncertainty analysis of the comparison of two scenarios is a useful means of highlighting the effects of correlation on uncertainty calculation. This article shows the importance of the analytical method in uncertainty calculation, which could lead to a more complete uncertainty analysis in LCA practice.
Insights into the oligomerization of CRMPs: crystal structure of human collapsin response mediator protein 5
Authors: Ponnusamy Rajesh , Lohkamp Bernhard 
Published: February 2013

AbstractCollapsin response mediator protein‐5 (CRMP‐5) is the latest identified member of the CRMP cytosolic phosphoprotein family, which is crucial for neuronal development and repair. CRMPs exist as homo‐ and/or hetero‐tetramers in vivo and participate in signaling transduction, cytoskeleton rearrangements, and endocytosis. CRMP‐5 antagonizes many of the other CRMPs' functions either by directly interacting with them or by competing for their binding partners. We determined the crystal structures of a full length and a truncated version of human CRMP‐5, both of which form a homo‐tetramer similar to those observed in CRMP‐1 and CRMP‐2. However, solution studies indicate that CRMP‐5 and CRMP‐1 form weaker homo‐tetramers compared with CRMP‐2, and that divalent cations, Ca2+ and Mg2+, destabilize oligomers of CRMP‐5 and CRMP‐1, but promote CRMP‐2 oligomerization. On the basis of comparative analysis of the CRMP‐5 crystal structure, we identified residues that are crucial for determining the preference for hetero‐oligomer or homo‐oligomer formation. We also show that in spite of being the CRMP family member most closely related to dihydropyrimidinase, CRMP‐5 does not have any detectable amidohydrolase activity. The presented findings provide new detailed insights into the structure, oligomerization, and regulation of CRMPs.
Polyploidy and microsatellite variation in the relict tree Prunus lusitanica L.: how effective are refugia in preserving genotypic diversity of clonal taxa?
Authors: García‐Verdugo C. , Calleja J. A. , Vargas P. , Silva L. , Moreira O. , Pulido F. 
Published: February 2013

AbstractRefugia are expected to preserve genetic variation of relict taxa, especially in polyploids, because high gene dosages could prevent genetic erosion in small isolated populations. However, other attributes linked to polyploidy, such as asexual reproduction, may strongly limit the levels of genetic variability in relict populations. Here, ploidy levels and patterns of genetic variation at nuclear microsatellite loci were analysed in Prunus lusitanica, a polyploid species with clonal reproduction that is considered a paradigmatic example of a Tertiary relict. Sampling in this study considered a total of 20 populations of three subspecies: mainland lusitanica (Iberian Peninsula and Morocco), and island azorica (Azores) and hixa (Canary Islands and Madeira). Flow cytometry results supported an octoploid genome for lusitanica and hixa, whereas a 16‐ploid level was inferred for azorica. Fixed heterozygosity of a few allele variants at most microsatellite loci resulted in levels of allelic diversity much lower than those expected for a high‐order polyploid. Islands as a whole did not contain higher levels of genetic variation (allelic or genotypic) than mainland refuges, but island populations displayed more private alleles and higher genotypic diversity in old volcanic areas. Patterns of microsatellite variation were compatible with the occurrence of clonal individuals in all but two island populations, and the incidence of clonality within populations negatively correlated with the estimated timing of colonization. Our results also suggest that gene flow has been very rare among populations, and thus population growth following founder events was apparently mediated by clonality rather than seed recruitment, especially in mainland areas. This study extends to clonal taxa the idea of oceanic islands as important refugia for biodiversity, since the conditions for generation and maintenance of clonal diversity (i.e. occasional events of sexual reproduction, mutation and/or seed immigration) appear to have been more frequent in these enclaves than in mainland areas.
Female‐biased dispersal in a bat with a female‐defence mating strategy
Authors: Nagy Martina , Günther Linus , Knörnschild Mirjam , Mayer Frieder 
Published: February 2013

AbstractThe ultimate causes for predominant male‐biased dispersal (MBD) in mammals and female‐biased dispersal (FBD) in birds are still subject to much debate. Studying exceptions to general patterns of dispersal, for example,FBDin mammals, provides a valuable opportunity to test the validity of proposed evolutionary pressures. We used long‐term behavioural and genetic data on individually banded Proboscis bats (Rhynchonycteris naso) to show that this species is one of the rare mammalian exceptions withFBD. Our results suggest that all females disperse from their natal colonies prior to first reproduction and that a substantial proportion of males are philopatric and reproduce in their natal colonies, although male immigration has also been detected. The age of females at first conception falls below the tenure of males, suggesting that females disperse to avoid father–daughter inbreeding. Male philopatry in this species is intriguing becauseProboscis bats do not share the usual mammalian correlates (i.e. resource‐defence polygyny and/or kin cooperation) of male philopatry. They have a mating strategy based on female defence, where local mate competition between male kin is supposedly severe and should prevent the evolution of male philopatry. However, in contrast to immigrant males, philopatric males may profit from acquaintance with the natal foraging grounds and may be able to attain dominance easier and/or earlier in life. Our results onProboscis bats lent additional support to the importance of inbreeding avoidance in shaping sex‐biased dispersal patterns and suggest that resource defence by males or kin cooperation cannot fully explain the evolution of male philopatry in mammals.
A complex life cycle in a warming planet: gene expression in thermally stressed sponges
Authors: Webster N. , Pantile R. , Botté E. , Abdo D. , Andreakis N. , Whalan S. 
Published: February 2013

AbstractSponges are abundant, diverse and functionally important components of aquatic biotopes with crucial associations for many reef fish and invertebrates. Sponges have strict temperature optima, and mass mortality events have occurred after unusually high temperatures. To assess how sponges may adapt to thermal stress associated with a changing climate, we applied gene expression profiling to both stages of their bipartite life cycles. Adult Rhopaloeides odorabile are highly sensitive to thermal stress (32 °C), yet their larvae can withstand temperatures up to 36 °C. Here, we reveal the molecular mechanisms that underpin these contrasting thermal tolerances, which may provide sponges with a means to successfully disperse into cooler waters. Heat shock protein 70 was induced by increasing temperature in adult sponges, and genes involved in important biological functions including cytoskeleton rearrangement, signal transduction, protein synthesis/degradation, oxidative stress and detoxification were all negatively correlated with temperature. Conversely, gene expression in larvae was not significantly affected until 36 °C when a stress response involving extremely rapid activation of heat shock proteins occurred. This study provides the first transcriptomic assessment of thermal stress on both life history stages of a marine invertebrate facilitating better predictions of the long‐term consequences of climate change for sponge population dynamics.
Triton's trident: cryptic Neogene divergences in a marine clam (Lasaea australis) correspond to Australia's three temperate biogeographic provinces
Authors: Li Jingchun , Ó Foighil Diarmaid , Park Joong‐Ki 
Published: February 2013

AbstractThe southern coast of Australia is composed of three distinct biogeographic provinces distinguished primarily by intertidal community composition. Several ecological mechanisms have been proposed to explain their formation and persistence, but no consensus has been reached. The marine clam Lasaea australis is arguably the most common bivalve on southern Australian rocky shores and occurs in all three provinces. Here, we tested if this species exhibits cryptic genetic structuring corresponding to the provinces and if so, what mechanisms potentially drove its divergence. Variation in two mitochondrial genes (16S and COIII) and one nuclear gene (ITS2) was assayed to test for genetic structuring and to reconstruct the clam's phylogenetic history. Our results showed that L. australis is comprised of three cryptic mitochondrial clades, each corresponding almost perfectly to one of the three biogeographic provinces. Divergence time estimates place their cladogenesis in the Neogene. The trident‐like topology and Neogene time frame of L. australis cladogenesis are incongruent with Quaternary vicariance predictions: a two‐clade topology produced by Pleistocene Bass Strait land bridge formation. We hypothesize that the interaction of the Middle Miocene Climate Transition with the specific geography of the southern coastline of Australia was the primary cladogenic driver in this clam lineage. Additional in‐depth studies of the endemic southern Australian marine biota across all three provinces are needed to establish the generality of this proposed older framework for regional cladogenesis.