Knee Pain Predicts Subsequent Shoulder Pain and the Association Is Mediated by Leg Weakness: Longitudinal Observational Data from the Osteoarthritis Initiative

Objective: To assess whether the ‘spread’ of joint pain is related to pain-associated muscle loss in one joint leading to increased loading and subsequent pain in other joints. Methods: Associations between persistent knee pain (pain in one or two knees over years 0-3 versus no persistent pain) and incident shoulder pain at year 4 were examined in participants from the longitudinal NIH Osteoarthritis Initiative (OAI). Associations were assessed using log multinomial modelling, adjusted for age, sex, BMI, depression score, other lower limb pain and baseline leg weakness (difficulty standing from a sitting position). Results: In older adults with clinically significant knee OA or at risk of knee OA (n=3486), the number of painful joints increased yearly, from 2.1 joints (95% CI 2.0, 2.2) at baseline increasing by 5.2% (95% CI 2.2%, 8.3%) at year 4. Shoulders were the next most commonly affected joint after knees (28.5%). Persistent pain in 1 or 2 knees increased risk of bilateral shoulder pain at year 4 (1 knee RR 1.59 (95% CI 0.97, 2.61); 2 knees RR 2.02 (1.17, 3.49)) after adjustment for confounders. Further adjustment for leg weakness attenuated effect sizes (1 knee RR 1.13 (95% CI 0.60, 2.11); 2 knees RR 1.44 (0.75, 2.77)), indicating mediation by functional leg weakness. Conclusions: Spread of joint pain is not random. Persistently painful knees predict new bilateral shoulder pain, which is likely mediated by leg weakness; suggesting that biomechanical factors influence the spread of pain

Detection of long repeat expansions from PCR-free whole-genome sequence data

Identifying large expansions of short tandem repeats (STRs) such as those that cause amyotrophic lateral sclerosis (ALS) and fragile X syndrome is challenging for short-read whole-genome sequencing (WGS) data. A solution to this problem is an important step towards integrating WGS into precision medicine. We have developed a software tool called ExpansionHunter that, using PCR-free WGS short-read data, can genotype repeats at the locus of interest, even if the expanded repeat is larger than the read length. We applied our algorithm to WGS data from 3,001 ALS patients who have been tested for the presence of the C9orf72 repeat expansion with repeat-primed PCR (RP-PCR). Compared against this truth data, ExpansionHunter correctly classified all (212/212, 95% CI [0.98, 1.00]) of the expanded samples as either expansions (208) or potential expansions (4). Additionally, 99.9% (2,786/2,789, 95% CI [0.997, 1.00]) of the wild type samples were correctly classified as wild type by this method with the remaining three samples identified as possible expansions. We further applied our algorithm to a set of 152 samples where every sample had one of eight different pathogenic repeat expansions including those associated with fragile X syndrome, Friedreich's ataxia and Huntington's disease and correctly flagged all but one of the known repeat expansions. Thus, ExpansionHunter can be used to accurately detect known pathogenic repeat expansions and provides researchers with a tool that can be used to identify new pathogenic repeat expansions. The software is licensed under GPL v3.0 and the source code is freely available on GitHub

Beyond Hybridity to the Politics of Scale: International Intervention and 'Local' Politics

The evident failures of international peacebuilding and statebuilding interventions (PSBIs) have recently prompted a focus on the interaction between interventions and target societies and states. Especially popular has been the ‘hybridity’ approach, which understands forms of peace and governance emerging through the mixing of local and international agendas and institutions. This article argues that hybridity is a highly problematic optic. Despite contrary claims, hybridity scholarship falsely dichotomizes ‘local’ and ‘international’ ideal-typical assemblages, and incorrectly presents outcomes as stemming from conflict and accommodation between them. Scholarship in political geography and state theory provides better tools for explaining PSBIs’ outcomes as reflecting socio-political contestation over power and resources. We theorize PSBIs as involving a politics of scale, where different social forces promote and resist alternative scales and modes of governance, depending on their interests and agendas. Contestation between these forces, which may be located at different scales and involved in complex, tactical, multi-scalar alliances, explains the uneven outcomes of international intervention. We demonstrate this using a case study of East Timor, focusing on decentralization and land policy

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Seismic image reconstruction using complex wavelets

The aim of seismic imaging is to reconstruct subsurface reflectivity from scattered acoustic data. In standard reconstruction techniques, the reflectivity model parameters are usually defined as a grid of point scatterers over the area or volume of the subsurface to be imaged. We propose an approach to subsurface imaging using the Dual Tree Complex Wavelet Transform (DT-CWT) as a basis for the reflectivity. This basis is used in conjunction with an iterative optimization which frames the problem as a linearized inverse scattering problem. We demonstrate the method on synthetic data and a marine seismic data set acquired over the Gippsland Basin near Australia. The technique is shown to reduce noise and processing artifacts while preserving discontinuities. It is likely to be particularly useful in cases where the acquired date is incomplete