3D Volumetric Modeling and Microvascular Reconstruction of Irradiated Lumbosacral Defects after Oncologic Resection

Background: Locoregional flaps are sufficient in most sacral reconstructions. However, large sacral defects due to malignancy necessitate a different reconstructive approach, with local flaps compromised by radiation and regional flaps inadequate for broad surface areas or substantial volume obliteration. In this report, we present our experience using free muscle transfer for volumetric reconstruction in such cases, and demonstrate 3D haptic models of the sacral defect to aid preoperative planning.Methods: Five consecutive patients with irradiated sacral defects secondary to oncologic resections were included, surface area ranging from 143-600cm2. Latissimus dorsi-based free flap sacral reconstruction was performed in each case, between 2005 and 2011. Where the superior gluteal artery was compromised, the subcostal artery was used as a recipient vessel. Microvascular technique, complications and outcomes are reported. The use of volumetric analysis and 3D printing is also demonstrated, with imaging data converted to 3D images suitable for 3D printing with Osirix software (Pixmeo, Geneva, Switzerland). An office-based, desktop 3D printer was used to print 3D models of sacral defects, used to demonstrate surface area and contour and produce a volumetric print of the dead space needed for flap obliteration. Results: The clinical series of latissimus dorsi free flap reconstructions is presented, with successful transfer in all cases, and adequate soft-tissue cover and volume obliteration achieved. The original use of the subcostal artery as a recipient vessel was successfully achieved. All wounds healed uneventfully. 3D printing is also demonstrated as a useful tool for 3D evaluation of volume and dead-space.Conclusion: Free flaps offer unique benefits in sacral reconstruction where local tissue is compromised by irradiation and tumor recurrence, and dead-space requires accurate volumetric reconstruction. We describe for the first time the use of the subcostal artery as a recipient in free flap sacral reconstruction. 3D printing of haptic bio-models is a rapidly evolving field with a substantial role in preoperative planning

Positional information resolves structural variations and uncovers an evolutionarily divergent genetic locus in accessions of Arabidopsis thaliana.

Genome sequencing of closely related individuals has yielded valuable insights that link genome evolution to phenotypic variations. However, advancement in sequencing technology has also led to an escalation in the number of poor quality–drafted genomes assembled based on reference genomes that can have highly divergent or haplotypic regions. The self-fertilizing nature of Arabidopsis thaliana poses an advantage to sequencing projects because its genome is mostly homozygous. To determine the accuracy of an Arabidopsis drafted genome in less conserved regions, we performed a resequencing experiment on a 3 ~71-kb genomic interval in the Landsberg erecta (Ler-0) accession. We identified novel structural variations (SVs) between Ler-0 and the reference accession Col-0 using a long-range polymerase chain reaction approach to generate an Illumina data set that has positional information, that is, a data set with reads that map to a known location. Positional information is important for accurate genome assembly and the resolution of SVs particularly in highly duplicated or repetitive regions. Sixty-one regions with misassembly signatures were identified from the Ler-0 draft, suggesting the presence of novel SVs that are not represented in the draft sequence. Sixty of those were resolved by iterative mapping using our data set. Fifteen large indels (>100 bp) identified from this study were found to be located either within protein-coding regions or upstream regulatory regions, suggesting the formation of novel alleles or altered regulation of existing genes in Ler-0. We propose future genome-sequencing experiments to follow a clone-based approach that incorporates positional information to ultimately reveal haplotype-specific differences between accessions

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

The perforator territories of the body: an anatomical and clinical study with the use of in-vivo angiography

Background: The cutaneous tissues of the body form the basis for a wide variety of flaps used in tissue transplantation for defects in after cancer resection or traumatic loss. These flaps require an intricate knowledge and fine dissection of the macrovascular and microvascular anatomy, and until recently, individual anatomy was only identifiable intraoperatively. Five years ago, advanced imaging technologies were introduced that enabled high resolution demonstration of this vascular anatomy preoperatively, enabling surgeons to effectively plan such surgery, and has since been shown to reduce a broad range of operative complications and facilitate faster and safer surgery. This imaging was first described for the abdominal wall vasculature, and the current researcher (WMR) was amoung the first to describe the imaging advances in this role. In over 100 peer-reviewed publications and fifty national and international presentations, the current researcher described the use of high resolution ultrasound, computed tomographic angiography (CTA), magnetic resonance angiography (MRA) and image-guided stereotaxy for imaging of the abdominal wall vasculature. With a view to achieving the same operative benefits for a much larger cohort of patients and a broader range of flaps, the current compilation of works investigates the use of advanced imaging technologies in a broad range of body regions. Methods: A clinical study of advanced imaging technologies was undertaken, imaging a range of cutaneous body regions in a cohort of over 500 patients. In all cases, the current researcher described all modifications to imaging protocols and undertook all software reconstructions for generation of three-dimensional reconstructions for use operatively. The reconstructive surgery and imaging was performed across five institutions. Results: The current study was able to accurately identify macrovascular and microvascular anatomy in all patients with a range of advanced imaging modalities. This was achievable using a range of hardware and software imaging modifications, and in particular, high resolution CTA was shown to be optimal in demonstrating such anatomy, and was able to be used throughout the body and in a broad range of patient ages and body habitus types. In addition to demonstrating that the use of such preoperative imaging techniques can result in reduced operative times, reduced donor site morbidity and reduced flap related complications, the imaging was also able to be used to design new flaps in reconstructive surgery. Conclusions: As finer details of the vascular anatomy of the integument of the body wall have become clinically relevant with refinements in surgical technique, individual differences have become increasingly apparent. This study has been able to develop new imaging modalities, CTA and MRA, for use in preoperative imaging, and has enabled the visualization of microvascular anatomy not previously able to be demonstrated in-vivo. Such imaging has since been shown to improve patient outcomes in reconstructive surgery