An approximate binary-black-hole metric

An approximate solution to Einstein's equations representing two widely-separated non-rotating black holes in a circular orbit is constructed by matching a post-Newtonian metric to two perturbed Schwarzschild metrics. The spacetime metric is presented in a single coordinate system valid up to the apparent horizons of the black holes. This metric could be useful in numerical simulations of binary black holes. Initial data extracted from this metric have the advantages of being linked to the early inspiral phase of the binary system, and of not containing spurious gravitational waves.Comment: 20 pages, 1 figure; some changes in Sec. IV B,C and Sec.

Retarded coordinates based at a world line, and the motion of a small black hole in an external universe

In the first part of this article I present a system of retarded coordinates based at an arbitrary world line of an arbitrary curved spacetime. The retarded-time coordinate labels forward light cones that are centered on the world line, the radial coordinate is an affine parameter on the null generators of these light cones, and the angular coordinates are constant on each of these generators. The spacetime metric in the retarded coordinates is displayed as an expansion in powers of the radial coordinate and expressed in terms of the world line's acceleration vector and the spacetime's Riemann tensor evaluated at the world line. The formalism is illustrated in two examples, the first involving a comoving world line of a spatially-flat cosmology, the other featuring an observer in circular motion in the Schwarzschild spacetime. The main application of the formalism is presented in the second part of the article, in which I consider the motion of a small black hole in an empty external universe. I use the retarded coordinates to construct the metric of the small black hole perturbed by the tidal field of the external universe, and the metric of the external universe perturbed by the presence of the black hole. Matching these metrics produces the MiSaTaQuWa equations of motion for the small black hole.Comment: 20 pages, revtex4, 2 figure

Radiation reaction and the self-force for a point mass in general relativity

A point particle of mass m moving on a geodesic creates a perturbation h, of the spacetime metric g, that diverges at the particle. Simple expressions are given for the singular m/r part of h and its quadrupole distortion caused by the spacetime. Subtracting these from h leaves a remainder h^R that is C^1. The self-force on the particle from its own gravitational field corrects the worldline at O(m) to be a geodesic of g+h^R. For the case that the particle is a small non-rotating black hole, an approximate solution to the Einstein equations is given with error of O(m^2) as m approaches 0.Comment: 4 pages, RevTe

Reconciling social norms with personal interests: indigenous styles of identity formation among Pakistani youth

Research on identity formation has been conducted mostly in Western contexts. We extend and complement such research by exploring qualitatively the strategies and styles of identity formation employed by emerging adults in Pakistan. Whereas Western theories of identity formation often provide a negative view of normative orientation as “blind obedience” without exploring alternatives, our thematic analysis of semi-structured interviews with 12 Pakistani emerging adults suggests a much more complex interplay between personal interests and normative influences on identity formation. Participants described various ways of reconciling normative expectations (parental, religious, and cultural) with their personal interests, preferences, and explorations, when deciding about their careers, relationships, and values. In Pakistani culture, normative influences seem to play a more positive and flexible role in identity formation than is suggested by previous Western research

From Geometry to Numerics: interdisciplinary aspects in mathematical and numerical relativity

This article reviews some aspects in the current relationship between mathematical and numerical General Relativity. Focus is placed on the description of isolated systems, with a particular emphasis on recent developments in the study of black holes. Ideas concerning asymptotic flatness, the initial value problem, the constraint equations, evolution formalisms, geometric inequalities and quasi-local black hole horizons are discussed on the light of the interaction between numerical and mathematical relativists.Comment: Topical review commissioned by Classical and Quantum Gravity. Discussion inspired by the workshop "From Geometry to Numerics" (Paris, 20-24 November, 2006), part of the "General Relativity Trimester" at the Institut Henri Poincare (Fall 2006). Comments and references added. Typos corrected. Submitted to Classical and Quantum Gravit

Evolving Spatio-temporal Data Machines Based on the NeuCube Neuromorphic Framework: Design Methodology and Selected Applications

The paper describes a new type of evolving connectionist systems (ECOS) called evolving spatio-temporal data machines based on neuromorphic, brain-like information processing principles (eSTDM). These are multi-modular computer systems designed to deal with large and fast spatio/spectro temporal data using spiking neural networks (SNN) as major processing modules. ECOS and eSTDM in particular can learn incrementally from data streams, can include ‘on the fly’ new input variables, new output class labels or regression outputs, can continuously adapt their structure and functionality, can be visualised and interpreted for new knowledge discovery and for a better understanding of the data and the processes that generated it. eSTDM can be used for early event prediction due to the ability of the SNN to spike early, before whole input vectors (they were trained on) are presented. A framework for building eSTDM called NeuCube along with a design methodology for building eSTDM using this are presented. The implementation of this framework in MATLAB, Java, and PyNN (Python) is presented. The latter facilitates the use of neuromorphic hardware platforms to run the eSTDM. Selected examples are given of eSTDM for pattern recognition and early event prediction on EEG data, fMRI data, multisensory seismic data, ecological data, climate data, audio-visual data. Future directions are discussed, including extension of the NeuCube framework for building neurogenetic eSTDM and also new applications of eSTDM

PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.Peer reviewe

Exome-wide somatic mutation characterization of small bowel adenocarcinoma

Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe

Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis

Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions.  Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated.  Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels.  Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months

Gender-sensitive Risks and Options Assessment for Decision making (ROAD) to support WiF2

The Gender-Sensitive Risks and Options Assessment for Decision Making (ROAD) to Support WiF-2 (ROAD migration project), a partnership coordinated by the International Food Policy Research Institute (IFPRI), Australian National University, American University Beirut, Lincoln University, and University of Dhaka, evaluated the ILO-DFID Partnership Programme on Fair Recruitment and Decent Work for Women Migrant Workers in South Asia and the Middle East (Work in Freedom, Phase 2 project [WiF-2]), which operated from 2018 to 2023. The WiF-2 project specifically aimed “to reduce vulnerability to trafficking and forced labour of women and girls across migration pathways leading to the care sector and textiles, clothing, leather and footwear industries (TCLFI) of South Asia and Arab States” (ToC WiF-2)