438 research outputs found

    Identification of Birds through DNA Barcodes

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    Short DNA sequences from a standardized region of the genome provide a DNA barcode for identifying species. Compiling a public library of DNA barcodes linked to named specimens could provide a new master key for identifying species, one whose power will rise with increased taxon coverage and with faster, cheaper sequencing. Recent work suggests that sequence diversity in a 648-bp region of the mitochondrial gene, cytochrome c oxidase I (COI), might serve as a DNA barcode for the identification of animal species. This study tested the effectiveness of a COI barcode in discriminating bird species, one of the largest and best-studied vertebrate groups. We determined COI barcodes for 260 species of North American birds and found that distinguishing species was generally straightforward. All species had a different COI barcode(s), and the differences between closely related species were, on average, 18 times higher than the differences within species. Our results identified four probable new species of North American birds, suggesting that a global survey will lead to the recognition of many additional bird species. The finding of large COI sequence differences between, as compared to small differences within, species confirms the effectiveness of COI barcodes for the identification of bird species. This result plus those from other groups of animals imply that a standard screening threshold of sequence difference (10× average intraspecific difference) could speed the discovery of new animal species. The growing evidence for the effectiveness of DNA barcodes as a basis for species identification supports an international exercise that has recently begun to assemble a comprehensive library of COI sequences linked to named specimens

    Hepatitis C virus dynamics among intravenous drug users suggest that an annual treatment uptake above 10% would eliminate the disease by 2030.

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    In Switzerland, the prevalence of hepatitis C virus (HCV) among people who inject drugs (PWID) has been decreasing owing to active harm reduction efforts and an aging population. Recent advances in HCV therapeutics may provide an opportunity to direct treatment to high-risk populations, with a goal of reducing HCV prevalence and preventing new infections. In order to guide these efforts, the current project was undertaken with the following aims: (1) to develop a simple model to estimate the number of new HCV infections using available data on PWID; (2) to examine the impact of intervention strategies (prevention and treatment) on new and total HCV infections among PWID. A dynamic HCV transmission model was used to track HCV incidence and prevalence among active PWID according to their harm reduction status. The relative impact of treating 1, 5, 10 or 15% of HCV+ PWID with new oral direct acting antivirals was considered. In 2015, there were an estimated 10 160 active PWID in Switzerland, more than 85% of whom were engaged in harm reduction programmes. Approximately 42% of active PWID were HCV-RNA+, with 55 new viraemic infections occurring annually. By 2030, a 60% reduction in the HCV+ PWID population would be expected. In the absence of behavioural changes, the number of secondary infections would increase under all treatment scenarios. With high level treatment, the number of secondary infections would peak and then drop, corresponding to depletion of the viral pool. In Switzerland, 5% treatment of the 2015 HCV+ PWID population per year would result in a 95% reduction in total cases by 2030, whereas ≥10% treatment would result in a >99% reduction. Timely treatment of hepatitis C virus among people who inject drugs is necessary to reduce the prevalence and prevent new infections in Switzerland

    Soft tissue sarcomas of the trunk wall (STS-TW): a study of 343 patients from the French Sarcoma Group (FSG) database

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    Background: Soft tissue sarcomas of the trunk wall (STS-TW) are usually studied together with soft tissue sarcomas of other locations. We report a study on STS-TW forming part of the French Sarcoma Group database. Patients and methods: Three hundred and forty-three adults were included. We carried out univariate and multivariate analysis for overall survival (OS), metastasis-free survival (MFS) and local recurrence-free survival (LRFS). Results: Tumor locations were as follows: thoracic wall, 82.5%; abdominal wall, 12.3% and pelvic wall, 5.2%. Median tumor size was 6.0 cm. The most frequent tumor types were unclassified sarcoma (27.7%) and myogenic sarcoma (19.2%). A total of 44.6% of cases were grade 3. In all, 21.9% of patients had a previous medical history of radiotherapy (PHR). Median follow-up was 7.6 years. The 5-year OS, MFS and LRFS rates were 60.4%, 68.9% and 58.4%, respectively. Multivariate analysis retained PHR and grade for predicting LRFS and PHR, size and grade as prognostic factors of MFS. Factors influencing OS were age, size, PHR, depth, grade and surgical margins. The predictive factors of incomplete response were PHR, size and T3. Conclusions: Our results suggest similar classical prognostic factors as compared with sarcomas of other locations. However, a separate analysis of STS-TW revealed a significant poor prognosis subgroup of patients with PH

    Limb salvage with isolated perfusion for soft tissue sarcoma: could less TNF-α be better?

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    Background: The optimal dose of TNF-α delivered by isolated limb perfusion (ILP) in patients with locally advanced soft tissue sarcoma is still unknown. Patients and methods: Randomised phase II trial comparing hyperthermic ILP (38-40°) with melphalan and one of the four assigned doses of TNF-α: 0.5 mg, 1 mg, 2 mg, and 3/4 mg upper/lower limb. The main end point was objective tumour response on MRI. Secondary end points were histological response, rate of amputation and toxicity. Resection of the remnant tumour was performed 2-3 months after ILP. The sample size was calculated assuming a linear increase of 10% in the objective response rates between each dose level group. Results: One hundred patients (25 per arm) were included. Thirteen per cent of patients had a systemic leakage with a cardiac toxicity in six patients correlated with high doses of TNF-α. Objective tumour responses were: 68%, 56%, 72% and 64% in the 0.5 mg, 1 mg, 2 mg and 3 or 4 mg arms, respectively (NS). Sixteen per cent of patients were not operated, 71% had a conservative surgery and 13% were amputated with no difference between the groups. With a median follow-up of 24 months, the 2 year overall and disease-free survival rates (95% CI) were 82% (73% to 89%) and 49% (39% to 59%), respectively. Conclusion: At the range of TNF-α doses tested, there was no dose effect detected for the objective tumour response, but systemic toxicity was significantly correlated with higher TNF-α doses. Efficacy and safety of low-dose TNF-α could greatly facilitate ILP procedures in the near futur

    Oxaliplatin-dacarbazine combination chemotherapy for the treatment of advanced soft tissue sarcoma of the limbs

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    <p>Abstract</p> <p>Background</p> <p>This study was designed to explore the feasibility, safety, and outcomes of pre-operative oxaliplatin-dacarbazine combination therapy for the treatment of advanced soft tissue sarcoma (STS) of the limb.</p> <p>Patients and Methods</p> <p>Between November 2005 and November 2008, 31 patients with advanced limb STS classified with stage IV STS were randomly assigned into experimental or control groups, and both were given 2 cycles of chemotherapy before undergoing surgery. The regimen for the experimental group was oxaliplatin (120 mg/m<sup>2</sup>, d<sub>1</sub>) in combination with dacarbazine (175 mg/m<sup>2</sup>, d<sub>13</sub>), while that for the control group was a standard vincristine, epirubicin, cyclophosphamide therapy. Operations were carried out four weeks after the second chemotherapy cycle, followed by another 24 more chemotherapy cycles of the previous regimen.</p> <p>Results</p> <p>Following preoperative chemotherapy, the experimental group exhibited a significant improvement in tumor regression compared to controls. Both regimens were well-tolerated, and no significant differences in adverse reactions were noted. At a median follow-up of 24 months, 28 patients were still alive and had normal limb function. The progression free survival rate of the experimental group was significantly higher than that of the control group (10/15 vs. 4/16, <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Oxaliplatin- dacarbazine neoadjuvant/adjuvant chemotherapy improved the prognosis of patients with advanced limb STS in comparison with vincristine, epirubicin, cyclophosphamide combination therapy.</p

    Real-Life Therapeutic Concentration Monitoring of Long-Acting Cabotegravir and Rilpivirine: Preliminary Results of an Ongoing Prospective Observational Study in Switzerland.

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    SHCS#879 is an ongoing Switzerland-wide multicenter observational study conducted within the Swiss HIV Cohort Study (SHCS) for the prospective follow-up of people living with HIV (PLWH) receiving long-acting injectable cabotegravir-rilpivirine (LAI-CAB/RPV). All adults under LAI-CAB/RPV and part of SHCS are enrolled in the project. The study addresses an integrated strategy of treatment monitoring outside the stringent frame of controlled clinical trials, based on relevant patient characteristics, clinical factors, potential drug-drug interactions, and measurement of circulating blood concentrations. So far, 91 blood samples from 46 PLWH have been collected. Most individuals are less than 50 years old, with relatively few comorbidities and comedications. The observed concentrations are globally in accordance with the available values reported in the randomized clinical trials. Yet, low RPV concentrations not exceeding twice the reported protein-adjusted 90% inhibitory concentration have been observed. Data available at present confirm a considerable between-patient variability overall. Based on the growing amount of PK data accumulated during this ongoing study, population pharmacokinetic analysis will characterize individual concentration-time profiles of LAI-CAB/RPV along with their variability in a real-life setting and their association with treatment response and tolerability, thus bringing key data for therapeutic monitoring and precision dosage adjustment of this novel long-acting therapy

    DNA barcoding of Brazilian sea turtles (Testudines)

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    Five out of the seven recognized species of sea turtles (Testudines) occur on the Brazilian coast. The Barcode Initiative is an effort to undertake a molecular inventory of Earth biodiversity. Cytochrome Oxidase c subunit I (COI) molecular tags for sea turtle species have not yet been described. In this study, COI sequences for the five species of sea turtles that occur in Brazil were generated. These presented widely divergent haplotypes. All observed values were on the same range as those already described for other animal groups: the overall mean distance was 8.2%, the mean distance between families (Dermochelyidae and Cheloniidae) 11.7%, the mean intraspecific divergence 0.34%, and the mean distance within Cheloniidae 6.4%, this being 19-fold higher than the mean divergence observed within species. We obtained species-specific COI barcode tags that can be used for identifying each of the marine turtle species studied

    Structural Analysis of Biodiversity

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    Large, recently-available genomic databases cover a wide range of life forms, suggesting opportunity for insights into genetic structure of biodiversity. In this study we refine our recently-described technique using indicator vectors to analyze and visualize nucleotide sequences. The indicator vector approach generates correlation matrices, dubbed Klee diagrams, which represent a novel way of assembling and viewing large genomic datasets. To explore its potential utility, here we apply the improved algorithm to a collection of almost 17000 DNA barcode sequences covering 12 widely-separated animal taxa, demonstrating that indicator vectors for classification gave correct assignment in all 11000 test cases. Indicator vector analysis revealed discontinuities corresponding to species- and higher-level taxonomic divisions, suggesting an efficient approach to classification of organisms from poorly-studied groups. As compared to standard distance metrics, indicator vectors preserve diagnostic character probabilities, enable automated classification of test sequences, and generate high-information density single-page displays. These results support application of indicator vectors for comparative analysis of large nucleotide data sets and raise prospect of gaining insight into broad-scale patterns in the genetic structure of biodiversity
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