The efficacy of continuous-flow cryo and cyclic compression therapy after hip fracture surgery on postoperative pain: design of a prospective, open-label, parallel, multicenter, randomized controlled, clinical trial

10.1186/s12891-016-1000-4BMC MUSCULOSKELETAL DISORDERS17

A high-quality human reference panel reveals the complexity and distribution of genomic structural variants

Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority of studies provide neither a global view of the full spectrum of these variants nor integrate them into reference panels of genetic variation. Here, we analyse whole genome sequencing data of 769 individuals from 250 Dutch families, and provide a haplotype-resolved map of 1.9 million genome variants across 9 different variant classes, including novel forms of complex indels, and retrotransposition-mediated insertions of mobile elements and processed RNAs. A large proportion are previously under reported variants sized between 21 and 100 bp. We detect 4 megabases of novel sequence, encoding 11 new transcripts. Finally, we show 191 known, trait-associated SNPs to be in strong linkage disequilibrium with SVs and demonstrate that our panel facilitates accurate imputation of SVs in unrelated individuals

Characteristics of de novo structural changes in the human genome.

Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions, and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1-20 bp) and 0.16 SVs (>20 bp) per generation. De novo structural changes affect on average 4.1 kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a nonuniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations

Whole-genome sequence variation, population structure and demographic history of the Dutch population

Whole-genome sequencing enables complete characterization of genetic variation, but geographic clustering of rare alleles demands many diverse populations be studied. Here we describe the Genome of the Netherlands (GoNL) Project, in which we sequenced the whole genomes of 250 Dutch parent-offspring families and constructed a haplotype map of 20.4 million single-nucleotide variants and 1.2 million insertions and deletions. The intermediate coverage (similar to 13x) and trio design enabled extensive characterization of structural variation, including midsize events (30-500 bp) previously poorly catalogued and de novo mutations. We demonstrate that the quality of the haplotypes boosts imputation accuracy in independent samples, especially for lower frequency alleles. Population genetic analyses demonstrate fine-scale structure across the country and support multiple ancient migrations, consistent with historical changes in sea level and flooding. The GoNL Project illustrates how single-population whole-genome sequencing can provide detailed characterization of genetic variation and may guide the design of future population studies

Tension band wiring for simple olecranon fractures: evaluation of surgical technique

Background: In some settings, specific techniques for open reduction and internal fixation are preferred based on the eminence of a surgeon or professional organization. An emphasis on technical aspects of surgery that are not proved superior and vary substantially from surgeon to surgeon can be confusing for trainees. This study applied a numerical grading of the technical aspects of tension band wire (TBW) fixation for olecranon fracture; assessed the interobserver agreement of each criterion; and measured the correlation of the technical grading and objective and subjective long-term outcomes. Materials and methods Forty observers were invited to rate the technical aspects of TBW fixation of the olecranon on 26 post-operative radiographs. The interobserver reliability of the rating was measured using the intra-class correlation coefficient. The correlation between the rating and motion, Mayo elbow performance index, and disabilities of the arm, shoulder and hand score was tested with the Spearman’s rank correlation test. Results: None of the figure-of-eight TBW constructs were considered perfect according to the numerical grading: the majority of observers found three deviations per fixation. The interobserver agreement was only fair for the total number of deviations and no correlation between the number of deviations and long-term objective and subjective outcome was found. Conclusions: A rating of the technical aspects of TBW for olecranon fractures was unreliable and did not correlate with subjective and objective outcomes. Emphasis on specific technical aspects of fixation might be confusing for trainees and could distract them from the principles of effective treatment. Level of evidence Level IV diagnostic study