Neoadjuvant chemoradiation compared to neoadjuvant radiation alone and surgery alone for Stage II and III soft tissue sarcoma of the extremities

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA).</p> <p>Methods</p> <p>We conducted a retrospective chart review of 112 cases.</p> <p>Results</p> <p>Treatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR.</p> <p>Conclusions</p> <p>NCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.</p

Revised valuation of flood regulation services of existing forest cover to inform natural capital accounts

This report provides updated evidence on the value of existing woodland in England, Scotland and Wales in regulating flood flows and reducing flood risk in downstream communities. This is a ground-breaking area of analysis that is attempting to improve on what was previously a significant evidence gap in the economic value of woodland. The study updates a previous evaluation (Broadmeadow et al., 2018) with improved estimates for the volume of flood water potentially removed by woodland or retained by its hydraulic roughness. The impacts of woodlands are compared with two alternative land uses, short grass and bare soil. The scope of the analysis was also extended to include the contribution of conifer woodlands, small woodlands, and trees outside of woodlands. A companion report (Fitch et al., 2022) is available that applies the approach to other natural capital types, including woodland, although values are not directly comparable due to methodological differences

Multi-Proxy Characterisation of the Storegga Tsunami and Its Impact on the Early Holocene Landscapes of the Southern North Sea

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC funded project No. 670518 LOST FRONTIERS, https://europa.eu/european-union/index_en, https://lostfrontiers.teamapp.com/). The project gratefully acknowledges the support of the Estonian Research Council (https://www.etag.ee/en/estonian-research-council/, Grant number: PUTJD829). PGS (https://www.pgs.com/) is acknowledged through provision of data used in this paper under license CA-BRAD-001-2017.Doggerland was a landmass occupying an area currently covered by the North Sea until marine inundation took place during the mid-Holocene, ultimately separating the British landmass from the rest of Europe. The Storegga Event, which triggered a tsunami reflected in sediment deposits in the northern North Sea, northeast coastlines of the British Isles and across the North Atlantic, was a major event during this transgressive phase. The spatial extent of the Storegga tsunami however remains unconfirmed as, to date, no direct evidence for the event has been recovered from the southern North Sea. We present evidence of a tsunami deposit in the southern North Sea at the head of a palaeo-river system that has been identified using seismic survey. The evidence, based on lithostratigraphy, geochemical signatures, macro and microfossils and sedimentary ancient DNA (sedaDNA), supported by optical stimulated luminescence (OSL) and radiocarbon dating, suggests that these deposits were a result of the tsunami. Seismic identification of this stratum and analysis of adjacent cores showed diminished traces of the tsunami which was largely removed by subsequent erosional processes. Our results confirm previous modelling of the impact of the tsunami within this area of the southern North Sea, and also indicate that these effects were temporary, localized, and mitigated by the dense woodland and topography of the area. We conclude that clear physical remnants of the wave in these areas are likely to be restricted to now buried, palaeo-inland basins and incised river valley systems.Publisher PDFPeer reviewe

Evolution of Anolis Lizard Dewlap Diversity

BACKGROUND: The dewlaps of Anolis lizards provide a classic example of a complex signaling system whose function and evolution is poorly understood. Dewlaps are flaps of skin beneath the chin that are extended and combined with head and body movements for visual signals and displays. They exhibit extensive morphological variation and are one of two cladistic features uniting anoles, yet little is known regarding their function and evolution. We quantified the diversity of anole dewlaps, investigated whether dewlap morphology was informative regarding phylogenetic relationships, and tested two separate hypotheses: (A) similar Anolis habitat specialists possess similar dewlap configurations (Ecomorph Convergence hypothesis), and (B) sympatric species differ in their dewlap morphologies to a greater extent than expected by chance (Species Recognition hypothesis). METHODOLOGY/PRINCIPAL FINDINGS: We found that dewlap configurations (sizes, patterns and colors) exhibit substantial diversity, but that most are easily categorized into six patterns that incorporate one to three of 13 recognizable colors. Dewlap morphology is not phylogenetically informative and, like other features of anoles, exhibits convergence in configurations. We found no support for the Ecomorph Convergence hypothesis; species using the same structural habitat were no more similar in dewlap configuration than expected by chance. With one exception, all sympatric species in four communities differ in dewlap configuration. However, this provides only weak support for the Species Recognition hypothesis because, due to the great diversity in dewlap configurations observed across each island, few cases of sympatric species with identical dewlaps would be expected to co-occur by chance alone. CONCLUSIONS/SIGNIFICANCE: Despite previous thought, most dewlaps exhibit easily characterizable patterns and colorations. Nevertheless, dewlap variation is extensive and explanations for the origin and evolution of this diversity are lacking. Our data do not support two hypothesized explanations for this diversity, but others such as sexual selection remain to be tested

Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance

Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in vitro. In this study, we examine Plasmodium Hb degradation in vivo in mice, using the parasite P. berghei, and show that it is possible to create mutant parasites lacking enzymes involved in the initial steps of Hb proteolysis. These mutants only complete development in reticulocytes and mature into both schizonts and gametocytes. Hb degradation is severely impaired and large amounts of undigested Hb remains in the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce little or no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of drug resistance. These findings have implications for drug development against human-malaria parasites, such as P. vivax and P. ovale, which develop inside reticulocytes

Exploring the Use of Cytochrome Oxidase c Subunit 1 (COI) for DNA Barcoding of Free-Living Marine Nematodes

BackgroundThe identification of free-living marine nematodes is difficult because of the paucity of easily scorable diagnostic morphological characters. Consequently, molecular identification tools could solve this problem. Unfortunately, hitherto most of these tools relied on 18S rDNA and 28S rDNA sequences, which often lack sufficient resolution at the species level. In contrast, only a few mitochondrial COI data are available for free-living marine nematodes. Therefore, we investigate the amplification and sequencing success of two partitions of the COI gene, the M1-M6 barcoding region and the I3-M11 partition.MethodologyBoth partitions were analysed in 41 nematode species from a wide phylogenetic range. The taxon specific primers for the I3-M11 partition outperformed the universal M1-M6 primers in terms of amplification success (87.8% vs. 65.8%, respectively) and produced a higher number of bidirectional COI sequences (65.8% vs 39.0%, respectively). A threshold value of 5% K2P genetic divergence marked a clear DNA barcoding gap separating intra- and interspecific distances: 99.3% of all interspecific comparisons were >0.05, while 99.5% of all intraspecific comparisons were <0.05 K2P distance.ConclusionThe I3-M11 partition reliably identifies a wide range of marine nematodes, and our data show the need for a strict scrutiny of the obtained sequences, since contamination, nuclear pseudogenes and endosymbionts may confuse nematode species identification by COI sequence

Genome-Wide Functional Divergence after the Symbiosis of Proteobacteria with Insects Unraveled through a Novel Computational Approach

Symbiosis has been among the most important evolutionary steps to generate biological complexity. The establishment of symbiosis required an intimate metabolic link between biological systems with different complexity levels. The strict endo-cellular symbiotic bacteria of insects are beautiful examples of the metabolic coupling between organisms belonging to different kingdoms, a eukaryote and a prokaryote. The host (eukaryote) provides the endosymbiont (prokaryote) with a stable cellular environment while the endosymbiont supplements the host's diet with essential metabolites. For such communication to take place, endosymbionts' genomes have suffered dramatic modifications and reconfigurations of proteins' functions. Two of the main modifications, loss of genes redundant for endosymbiotic bacteria or the host and bacterial genome streamlining, have been extensively studied. However, no studies have accounted for possible functional shifts in the endosymbiotic proteomes. Here, we develop a simple method to screen genomes for evidence of functional divergence between two species clusters, and we apply it to identify functional shifts in the endosymbiotic proteomes. Despite the strong effects of genetic drift in the endosymbiotic systems, we unexpectedly identified genes to be under stronger selective constraints in endosymbionts of aphids and ants than in their free-living bacterial relatives. These genes are directly involved in supplementing the host's diet with essential metabolites. A test of functional divergence supports a strong relationship between the endosymbiosis and the functional shifts of proteins involved in the metabolic communication with the insect host. The correlation between functional divergence in the endosymbiotic bacterium and the ecological requirements of the host uncovers their intimate biochemical and metabolic communication and provides insights on the role of symbiosis in generating species diversity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead