An evaluation of the structural validity of the Shoulder Pain and Disability Index (SPADI) using the Rasch model

Purpose: The Shoulder Pain and Disability Index (SPADI) has been extensively evaluated for its psychometric properties using classic test theory (CTT). The purpose of this study was to evaluate its structural validity using Rasch model analysis. Methods: Responses to the SPADI from 1030 patients referred for physiotherapy with shoulder pain and enrolled in a prospective cohort study were available for Rasch model analysis. Overall fit, individual person and item fit, response format, dependence, unidimensionality, targeting, reliability and differential item functioning (DIF) were examined. Results: The SPADI pain subscale initially demonstrated a misfit due to DIF by age and gender. After iterative analysis it showed good fit to the Rasch model with acceptable targeting and unidimensionality (overall fit (chi-square statistic 57.2, p=0.1); mean item fit residual 0.19 (1.5) and mean person fit residual 0.44 (1.1); person separation index (PSI) of 0.83). The disability subscale however shows significant misfit due to uniform DIF even after iterative analyses were used to explore different solutions to the sources of misfit (overall fit (chi-square statistic 57.2, p=0.1); mean item fit residual -0.54 (1.26) and mean person fit residual -0.38 (1.0); PSI 0.84). Conclusions: Rasch Model analysis of the SPADI has identified some strengths and limitations not previously observed using CTT methods. The SPADI should be treated as two separate subscales. The SPADI is a widely used outcome measure in clinical practice and research, however the scores derived from it must be interpreted with caution. The pain subscale fits the Rasch model expectations well. The disability subscale does not fit the Rasch model and its current format does not meet the criteria for true interval-level measurement required for use as a primary endpoint in clinical trials. Clinicians should therefore exercise caution when interpreting score changes on the disability subscale and attempt to compare their scores to age and sex stratified data

Return of naturally sourced Pb to Atlantic surface waters

Anthropogenic emissions completely overwhelmed natural marine lead (Pb) sources during the past century, predominantly due to leaded petrol usage. Here, based on Pb isotope measurements, we reassess the importance of natural and anthropogenic Pb sources to the tropical North Atlantic following the nearly complete global cessation of leaded petrol use. Significant proportions of up to 30-50% of natural Pb, derived from mineral dust, are observed in Atlantic surface waters, reflecting the success of the global effort to reduce anthropogenic Pb emissions. The observation of mineral dust derived Pb in surface waters is governed by the elevated atmospheric mineral dust concentration of the North African dust plume and the dominance of dry deposition for the atmospheric aerosol flux to surface waters. Given these specific regional conditions, emissions from anthropogenic activities will remain the dominant global marine Pb source, even in the absence of leaded petrol combustion

Genome-wide repeat dynamics reflect phylogenetic distance in closely related allotetraploid Nicotiana (Solanaceae)

Nicotiana sect. Repandae is a group of four allotetraploid species originating from a single allopolyploidisation event approximately 5 million years ago. Previous phylogenetic analyses support the hypothesis of N. nudicaulis as sister to the other three species. This is concordant with changes in genome size, separating those with genome downsizing (N. nudicaulis) from those with genome upsizing (N. repanda, N. nesophila, N. stocktonii). However, a recent analysis reflecting genome dynamics of different transposable element families reconstructed greater similarity between N. nudicaulis and the Revillagigedo Island taxa (N. nesophila and N. stocktonii), thereby placing N. repanda as sister to the rest of the group. This could reflect a different phylogenetic hypothesis or the unique evolutionary history of these particular elements. Here we re-examine relationships in this group and investigate genome-wide patterns in repetitive DNA, utilising high-throughput sequencing and a genome skimming approach. Repetitive DNA clusters provide support for N. nudicaulis as sister to the rest of the section, with N. repanda sister to the two Revillagigedo Island species. Clade-specific patterns in the occurrence and abundance of particular repeats confirm the original (N. nudicaulis (N. repanda (N. nesophila ? N. stocktonii))) hypothesis. Furthermore, overall repeat dynamics in the island species N. nesophila and N. stocktonii confirm their similarity to N. repanda and the distinctive patterns between these three species and N. nudicaulis. Together these results suggest that broad-scale repeat dynamics do in fact reflect evolutionary history and could be predicted based on phylogenetic distance

Independent, Rapid and Targeted Loss of Highly Repetitive DNA in Natural and Synthetic Allopolyploids of Nicotiana tabacum

Allopolyploidy (interspecific hybridisation and polyploidy) has played a significant role in the evolutionary history of angiosperms and can result in genomic, epigenetic and transcriptomic perturbations. We examine the immediate effects of allopolyploidy on repetitive DNA by comparing the genomes of synthetic and natural Nicotiana tabacum with diploid progenitors N. tomentosiformis (paternal progenitor) and N. sylvestris (maternal progenitor). Using next generation sequencing, a recently developed graph-based repeat identification pipeline, Southern blot and fluorescence in situ hybridisation (FISH) we characterise two highly repetitive DNA sequences (NicCL3 and NicCL7/30). Analysis of two independent high-throughput DNA sequencing datasets indicates NicCL3 forms 1.6–1.9% of the genome in N. tomentosiformis, sequences that occur in multiple, discontinuous tandem arrays scattered over several chromosomes. Abundance estimates, based on sequencing depth, indicate NicCL3 is almost absent in N. sylvestris and has been dramatically reduced in copy number in the allopolyploid N. tabacum. Surprisingly elimination of NicCL3 is repeated in some synthetic lines of N. tabacum in their forth generation. The retroelement NicCL7/30, which occurs interspersed with NicCL3, is also under-represented but to a much lesser degree, revealing targeted elimination of the latter. Analysis of paired-end sequencing data indicates the tandem component of NicCL3 has been preferentially removed in natural N. tabacum, increasing the proportion of the dispersed component. This occurs across multiple blocks of discontinuous repeats and based on the distribution of nucleotide similarity among NicCL3 units, was concurrent with rounds of sequence homogenisation

Independent Origins of Cultivated Coconut (Cocos nucifera L.) in the Old World Tropics

As a portable source of food, water, fuel, and construction materials, the coconut (Cocos nucifera L.) played a fundamental role in human migrations and the development of civilization across the humid tropics. Here we investigated the coconut's domestication history and its population genetic structure as it relates to human dispersal patterns. A sample of 1,322 coconut accessions, representing the geographical and phenotypic diversity of the species, was examined using ten microsatellite loci. Bayesian analyses reveal two highly genetically differentiated subpopulations that correspond to the Pacific and Indo-Atlantic oceanic basins. This pattern suggests independent origins of coconut cultivation in these two world regions, with persistent population structure on a global scale despite long-term human cultivation and dispersal. Pacific coconuts show additional genetic substructure corresponding to phenotypic and geographical subgroups; moreover, the traits that are most clearly associated with selection under human cultivation (dwarf habit, self-pollination, and “niu vai” fruit morphology) arose only in the Pacific. Coconuts that show evidence of genetic admixture between the Pacific and Indo-Atlantic groups occur primarily in the southwestern Indian Ocean. This pattern is consistent with human introductions of Pacific coconuts along the ancient Austronesian trade route connecting Madagascar to Southeast Asia. Admixture in coastal east Africa may also reflect later historic Arab trading along the Indian Ocean coastline. We propose two geographical origins of coconut cultivation: island Southeast Asia and southern margins of the Indian subcontinent

Comparative costs and activity from a sample of UK clinical trials units

Background: The costs of medical research are a concern. Clinical Trials Units (CTUs) need to better understand variations in the costs of their activities. Methods: Representatives of ten CTUs and two grant-awarding bodies pooled their experiences in discussions over 1.5 years. Five of the CTUs provided estimates of, and written justification for, costs associated with CTU activities required to implement an identical protocol. The protocol described a 5.5-year, nonpharmacological randomized controlled trial (RCT) conducted at 20 centres. Direct and indirect costs, the number of full time equivalents (FTEs) and the FTEs attracting overheads were compared and qualitative methods (unstructured interviews and thematic analysis) were used to interpret the results. Four members of the group (funding-body representatives or award panel members) reviewed the justification statements for transparency and information content. Separately, 163 activities common to trials were assigned to roles used by nine CTUs; the consistency of role delineation was assessed by Cohen's κ. Results: Median full economic cost of CTU activities was £769,637 (range: £661,112 to £1,383,323). Indirect costs varied considerably, accounting for between 15% and 59% (median 35%) of the full economic cost of the grant. Excluding one CTU, which used external statisticians, the total number of FTEs ranged from 2.0 to 3.0; total FTEs attracting overheads ranged from 0.3 to 2.0. Variation in directly incurred staff costs depended on whether CTUs: supported particular roles from core funding rather than grants; opted not to cost certain activities into the grant; assigned clerical or data management tasks to research or administrative staff; employed extensive on-site monitoring strategies (also the main source of variation in non-staff costs). Funders preferred written justifications of costs that described both FTEs and indicative tasks for funded roles, with itemised non-staff costs. Consistency in role delineation was fair (κ = 0.21-0.40) for statisticians/data managers and poor for other roles (κ < 0.20). Conclusions: Some variation in costs is due to factors outside the control of CTUs such as access to core funding and levels of indirect costs levied by host institutions. Research is needed on strategies to control costs appropriately, especially the implementation of risk-based monitoring strategies

There's No Place Like Home: Crown-of-Thorns Outbreaks in the Central Pacific Are Regionally Derived and Independent Events

One of the most significant biological disturbances on a tropical coral reef is a population outbreak of the fecund, corallivorous crown-of-thorns sea star, Acanthaster planci. Although the factors that trigger an initial outbreak may vary, successive outbreaks within and across regions are assumed to spread via the planktonic larvae released from a primary outbreak. This secondary outbreak hypothesis is predominantly based on the high dispersal potential of A. planci and the assertion that outbreak populations (a rogue subset of the larger population) are genetically more similar to each other than they are to low-density non-outbreak populations. Here we use molecular techniques to evaluate the spatial scale at which A. planci outbreaks can propagate via larval dispersal in the central Pacific Ocean by inferring the location and severity of gene flow restrictions from the analysis of mtDNA control region sequence (656 specimens, 17 non-outbreak and six outbreak locations, six archipelagos, and three regions). Substantial regional, archipelagic, and subarchipelagic-scale genetic structuring of A. planci populations indicate that larvae rarely realize their dispersal potential and outbreaks in the central Pacific do not spread across the expanses of open ocean. On a finer scale, genetic partitioning was detected within two of three islands with multiple sampling sites. The finest spatial structure was detected at Pearl & Hermes Atoll, between the lagoon and forereef habitats (<10 km). Despite using a genetic marker capable of revealing subtle partitioning, we found no evidence that outbreaks were a rogue genetic subset of a greater population. Overall, outbreaks that occur at similar times across population partitions are genetically independent and likely due to nutrient inputs and similar climatic and ecological conditions that conspire to fuel plankton blooms