Influence of human leukocyte antigen (HLA) alleles and killer cell immunoglobulin-like receptors (KIR) types on heparin-induced thrombocytopenia (HIT)

Objectives Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT.\ud Methods HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina® OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. P values for HLA and KIR association were corrected using a false discovery rate (FDR) q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Results Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81[1.57-5.02], p=2.1x10-4, q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). Conclusions The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary

Exploring the genomic basis of early childhood caries: a pilot study

Objective: A genetic component in early childhood caries (ECC) is theorized, but no genome-wide investigations of ECC have been conducted. This pilot study is part of a long-term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC-associated genetic loci. Methods: The study's community-based sample comprised 212 children (mean age=39 months; range = 30–52 months; males = 55%; Hispanic/Latino = 35%, African-American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%). Approximately 2.4 million single nucleotide polymorphisms (SNPs) were genotyped using DNA purified from saliva. A P &lt; 5 × 10−8 criterion was used for genome-wide significance. SNPs with P &lt; 5 × 10−5 were followed-up in three independent cohorts of 921 preschool-age children with similar ECC prevalence. Results: SNPs with minor allele frequency ≥5% explained 52% (standard error = 54%) of ECC variance (one-sided P = 0.03). Unsurprisingly, given the pilot's small sample size, no genome-wide significant associations were found. An intergenic locus on 4q32 (rs4690994) displayed the strongest association with ECC [P = 2.3 × 10−6; odds ratio (OR) = 3.5; 95% confidence interval (CI) = 2.1–5.9]. Thirteen loci with suggestive associations were followed-up – none showed evidence of association in the replication samples. Conclusion: This study's findings support a heritable component of ECC and demonstrate the feasibility of conducting genomics studies among preschool-age children

Modeling of the condyle elements within a biomechanical knee model

The development of a computational multibody knee model able to capture some of the fundamental properties of the human knee articulation is presented. This desideratum is reached by including the kinetics of the real knee articulation. The research question is whether an accurate modeling of the condyle contact in the knee will lead to reproduction of the complex combination of flexion/extension, abduction/adduction and tibial rotation ob-served in the real knee? The model is composed by two anatomic segments, the tibia and the femur, whose characteristics are functions of the geometric and anatomic properties of the real bones. The biomechanical model characterization is developed under the framework of multibody systems methodologies using Cartesian coordinates. The type of approach used in the proposed knee model is the joint surface contact conditions between ellipsoids, represent-ing the two femoral condyles, and points, representing the tibial plateau and the menisci. These elements are closely fitted to the actual knee geometry. This task is undertaken by con-sidering a parameter optimization process to replicate experimental data published in the lit-erature, namely that by Lafortune and his co-workers in 1992. Then, kinematic data in the form of flexion/extension patterns are imposed on the model corresponding to the stance phase of the human gait. From the results obtained, by performing several computational simulations, it can be observed that the knee model approximates the average secondary mo-tion patterns observed in the literature. Because the literature reports considerable inter-individual differences in the secondary motion patterns, the knee model presented here is also used to check whether it is possible to reproduce the observed differences with reasonable variations of bone shape parameters. This task is accomplished by a parameter study, in which the main variables that define the geometry of condyles are taken into account. It was observed that the data reveal a difference in secondary kinematics of the knee in flexion ver-sus extension. The likely explanation for this fact is the elastic component of the secondary motions created by the combination of joint forces and soft tissue deformations. The proposed knee model is, therefore, used to investigate whether this observed behavior can be explained by reasonable elastic deformations of the points representing the menisci in the model.Fundação para a Ciência e a Tecnologia (FCT) - PROPAFE – Design and Development of a Patello-Femoral Prosthesis (PTDC/EME-PME/67687/2006), DACHOR - Multibody Dynamics and Control of Hybrid Active Orthoses MIT-Pt/BSHHMS/0042/2008, BIOJOINTS - Development of advanced biological joint models for human locomotion biomechanics (PTDC/EME-PME/099764/2008)

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Espécies crípticas em Pagamea coriacea sensu lato (Rubiaceae): evidências morfológicas, ecológicas e de comportamento reprodutivo em um contexto simpátrico

In this study we explore morphological and ecological variation in sympatric populations of Pagamea coriacea s.l. - a species complex from white-sand vegetation in the Amazon. A total of 147 trees were sampled and monitored at three nearby sites in Central Amazon, Brazil. Multivariate analyses of morphology indicated two distinct groups (A and B), which also differed in bark type, each containing subgroups associated with sexual dimorphism. However, a single hermaphroditic individual was observed within group B. As expected, all pistillate plants produced fruits, but 23% of the staminate plants of group B, and 5% of group A also produced fruits. This variation suggests that the sexual systems of both groups are between dioecy and gynodioecy. There was an overlap in flowering phases between the two groups, but the pattern of floral maturation differed. Ecologically, plants of group B were found in more shaded habitats and over sandstone bedrocks, while group A was prevalent in deeper sandy soils as canopy plants. The significances of morphological and environmental differences were tested by a multivariate analysis of variance, and a canonical discriminant analysis assessed the importance of variables. The coexistence in sympatry of two discrete morphological groups in the P. coriacea s.l., with different habitat preferences and reproductive behaviors, indicates they represent distinct species.O objetivo deste estudo foi testar se o complexo de espécies Pagamea coriacea inclui múltiplas espécies, usando evidências morfológicas, ecológicas e de comportamento reprodutivo. Um total de 147 árvores foram amostradas e monitoradas em três locais próximos na Amazônia Central, Brasil. Análises multivariadas de dados morfológicos indicaram dois grupos discretos (A e B), que coincidem com diferenças no tipo de casca, cada um por sua vez com subgrupos que representam dimorfismo sexual. Contudo, um indivíduo distintamente hermafrodita foi encontrado no grupo B. Todas as plantas pistiladas produziram frutos, mas também foram observados frutos para 23% das plantas estaminadas do grupo B, e para 5% das estaminadas do grupo A. Essa variação sugere que ambos grupos possuem um sistema sexual entre dioicia e ginodioicia. Houve sobreposição das fases de floração e frutificação entre os dois grupos, mas o padrão de maturação de flores foi diferente. Quanto ao hábitat, o grupo B predominou em situações de sombra e em solos arenosos rasos sobre lajes de pedra, enquanto o grupo A ocorreu em solos arenosos mais profundos e no dossel da vegetação. A coexistência de dois grupos morfológicos discretos no complexo P. coriacea s.l., com diferenças ecológicas e de comportamento reprodutivo, indica que correspondem a duas espécies distintas