scholarly journals Genomic Biosurveillance Detects A Sexual Hybrid in the Sudden Oak Death Pathogen

2021 ◽  
Author(s):  
Richard Hamelin ◽  
Guillaume Bilodeau ◽  
Renate Heinzelmann ◽  
Kelly Hrywkiw ◽  
Arnaud Capron ◽  
...  
Keyword(s):  
Phytophthora Ramorum ◽  
Term Survival ◽  
Plant Nursery ◽  
Sexual Recombination ◽  
Novel Variants ◽  
Exotic Pathogens ◽  
Sexual Hybrid ◽  
Host Infection ◽  
And Control ◽  
Invasive Exotic

Abstract Invasive exotic pathogens pose a threat to trees and forest ecosystems worldwide1, hampering the provision of essential ecosystem services such as carbon sequestration and water purification2. Hybridization is a major evolutionary force that can drive the emergence of pathogens3. Phytophthora ramorum, an emergent pathogen that causes the sudden oak and larch death, spreads as reproductively isolated divergent clonal lineages. Sexual recombination has never been reported in this pathogen under natural conditions and laboratory crosses have yielded unfit progenies, suggesting postzygotic barriers to hybridization. Here we report the discovery in a plant nursery of novel variants of P. ramorum that are the result of homoploid hybridization via sexual recombination between North American and European lineages of the pathogen. We show that these hybrids are viable, can infect plants and produce spores for long-term survival and propagation. Genome sequencing revealed novel genotypic combinations, not present in the parental lineages, at 54,515 single nucleotide polymorphism loci. More than 6000 of the novel genotypes at these loci are predicted to have a functional impact in genes associated with host infection, including effectors, carbohydrate-active enzymes and proteases. We also observed post-meiotic mitotic recombination that could generate additional genotypic and phenotypic variation and contribute to homoploid hybrid speciation. Our study highlights the importance of plant pathogen biosurveillance to detect novel variants and inform management and control.

scholarly journals The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review

2021 ◽  
Vol 28 ◽  
pp. 107327482199743
Author(s):  
Ke Chen ◽  
Xiao Wang ◽  
Liu Yang ◽  
Zheling Chen
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Survival Rate ◽  
Meta Analysis ◽  
Response Rates ◽  
Control Group ◽  
Term Survival ◽  
Long Term Survival ◽  
And Control

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.

Prognostic selection and long-term survival analysis to assess overdiagnosis risk in lung cancer screening randomized trials

2020 ◽  
pp. 096914132092303
Author(s):  
Eugenio Paci ◽  
Donella Puliti ◽  
Francesca Maria Carozzi ◽  
Laura Carrozzi ◽  
Fabio Falaschi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Survival Rates ◽  
Lung Cancer Screening ◽  
Term Survival ◽  
Long Term Survival ◽  
And Control ◽  
Screening Trial

Objectives Overdiagnosis in low-dose computed tomography randomized screening trials varies from 0 to 67%. The National Lung Screening Trial (extended follow-up) and ITALUNG (Italian Lung Cancer Screening Trial) have reported cumulative incidence estimates at long-term follow-up showing low or no overdiagnosis. The Danish Lung Cancer Screening Trial attributed the high overdiagnosis estimate to a likely selection for risk of the active arm. Here, we applied a method already used in benefit and overdiagnosis assessments to compute the long-term survival rates in the ITALUNG arms in order to confirm incidence-excess method assessment. Methods Subjects in the active arm were invited for four screening rounds, while controls were in usual care. Follow-up was extended to 11.3 years. Kaplan-Meyer 5- and 10-year survivals of “resected and early” (stage I or II and resected) and “unresected or late” (stage III or IV or not resected or unclassified) lung cancer cases were compared between arms. Results The updated ITALUNG control arm cumulative incidence rate was lower than in the active arm, but this was not statistically significant (RR: 0.89; 95% CI: 0.67–1.18). A compensatory drop of late cases was observed after baseline screening. The proportion of “resected and early” cases was 38% and 19%, in the active and control arms, respectively. The 10-year survival rates were 64% and 60% in the active and control arms, respectively ( p = 0.689). The five-year survival rates for “unresected or late” cases were 10% and 7% in the active and control arms, respectively ( p = 0.679). Conclusions This long-term survival analysis, by prognostic categories, concluded against the long-term risk of overdiagnosis and contributed to revealing how screening works.

Randomized trial of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with primary advanced peritoneal, ovarian, and tubal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5520-5520 ◽  
Author(s):  
Myong Cheol Lim ◽  
Suk-Joon Chang ◽  
Heong Jong Yoo ◽  
Byung-Ho Nam ◽  
Robert Bristow ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Residual Tumor ◽  
Study Endpoint ◽  
Rank Test ◽  
Control Group ◽  
Term Survival ◽  
Log Rank Test ◽  
And Control ◽  
The Impact

5520 Background: Cytoreductive surgery followed by taxane and platinum-based chemotherapy is standard treatment for advanced ovarian cancer. We compared results of randomly allocated HIPEC in primary advanced epithelial ovarian cancer who have optimal cytoreductive surgery in this prospective randomized multicenter trial. The study endpoint is to evaluate progression free survival (PFS) and overall survival (OS). Methods: 184 patients staged III and IV were randomly allocated to trial arm (HIPEC, cisplatin 75 mg/m2, 90 min) or control arm (no HIPEC), intraoperatively based on residual tumor (size <1cm) from July 2010 to January 2016. The groups were well balanced according to the age, body mass index, performance status, stage, histology, serum CA125 level, and use of neoadjuvant chemotherapy (NAC) at study entry. Results: 184 pts (HIPEC, 92; control, 92) were included in this preplanned analysis. No mortality after surgery ± HIPEC was identified in both groups. Postoperative outcomes including extent of surgery, estimated blood loss, residual tumor, and hospitalization day were not different between both group, except operation time (487 vs. 404 min, p<0.001) due to HIPEC procedure. The most common adverse event was anemia: 67.4% in HIPEC and 50% in control group (p=0.025). The other toxicity common in HIPEC group is the elevation of creatinine (15.2% vs. 4.3%, p=0.026). There were no differences between both groups for transfusion (35.9 vs. 29.3, p=0.432), neutropenia (19.6 vs. 10.9%, p=0.151), and thrombocytopenia (9.8 vs. 3.3%, p=0.136). Two-year PFS was 43.2% and 43.5% and 5-year PFS was 20.9% and 16.0% in HIPEC and control group, respectively (p=0.569). Five-year OS was 51.0% and 49.4% in HIPEC and control group, respectively (p=0.574). In women who received NAC, the median PFS for HIPEC and control group were 20 and 19 months, respectively (log-rank test, p = 0.137) and the median OS for HIPEC and control group were 54 and 51 months, respectively (log-rank test, p = 0.407). In the subgroup with NAC, 2-year PFS was 37.2% in HIPEC group and 29.5% in control group and 5-year OS was 47.9% in HIPEC group and 27.7% in control group. After 20 months in PFS and 30 months in OS, two survival curves in women who received NAC showed the trend of gradual distinction, favoring HIPEC group. Conclusions: No mortality was identified and postoperative morbidities were not statistically different between two groups except anemia and creatinine elevation in HIPEC group. The survival analysis did not show the statistical superiority of the HIPEC arm. More follow-up is required to confirm the impact of HIPEC on long-term survival outcome in ovarian cancer, especially in NAC group. Clinical trial information: NCT01091636.

scholarly journals IMMU-02. CH14.18 IN THE TREATMENT OF HIGH-RISK NEUROBLASTOMA: A META-ANALYSIS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i27-i27
Author(s):  
Sameerah Abdel-Khaleq ◽  
Lina Alim ◽  
Atholl Johnston ◽  
Khloud Adam
Keyword(s):  
High Risk ◽  
Effect Size ◽  
Standard Error ◽  
Meta Analysis ◽  
Combined Effect ◽  
Bibliographic Databases ◽  
Survival Outcomes ◽  
Weighted Mean ◽  
Term Survival ◽  
And Control

Abstract High-risk neuroblastoma (HRNB) is a rare malignancy that mainly affects young children. Long-term survival remains low despite aggressive, multimodal treatment regimens. The aim is to assess the effect of Ch14.18, a novel anti-GD2 antibody, on survival in HRNB. In this meta-analysis, Pubmed/MEDLINE, EMBASE, Cochrane CENTRAL and Clinicaltrials.gov bibliographic databases were searched from inception to 1st July 2018. Prospective or retrospective interventional clinical trials with at least two arms or observational cohort or case-control studies were eligible. Participants had to have HRNB. Ch14.18 was the intervention of choice. Any control, comparator treatments were accepted. Studies were appraised for inclusion by two independent reviewers. Data was extracted from published reports. Primary outcomes assessed were Event-Free Survival (EFS) and Overall Survival (OS) and presented as Weighted Mean EFS (%) ± Standard Error (SE) and Weighted Mean OS (%) ± Standard Error (SE), respectively. Combined effect size was elicited for EFS±SE and OS±SE. The search yielded 367 results of which 7 studies conducted on 1727 patients were eligible for inclusion. The weighted mean EFS±SE for Ch14.18 regimens (n=779) and control regimens (n=787) were 55.6±2.0% and 41.2±1.7%, respectively. The weighted mean OS±SE for Ch14.18 regimens (n=430) and control regimens (n=348) were 63.4±2.3% and 53.6±2.7%, respectively. Results of the meta analysis yielded statistical power &gt;94%. The combined effect size of Ch14.18 regimens for EFS±SE was 0.2907±0.05 [95% CI: 0.19–0.39, p&lt;0.001] and the combined effect size for OS±SE was 0.26±0.07 [95% CI: 0.11- 0.4, p&lt;0.001]. Significant superior survival outcomes were achieved with the use of Ch14.18 in the treatment of HRNB. These findings support using Ch14.18 as an adjunct in maintenance therapy in high-risk neuroblastoma. This meta analysis is the first of its kind. Survival outcomes are to be interpreted with caution due to confounding bias.

scholarly journals An Overview of Microfinance Service Practices in Nepal

2012 ◽  
Vol 7 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Pushpa Raj Sharma
Keyword(s):  
Critical Mass ◽  
Bottom Line ◽  
Term Survival ◽  
Social Mission ◽  
Business Studies ◽  
Provision Of Services ◽  
Market Responsiveness ◽  
Development Approach ◽  
And Control

Microfinance is not simply banking for the poor; it is a development approach with a social mission and a private sector-based financial bottom line that uses tested and continually adjusted sets of principles, practices and technologies. The key to successful microfinance lies in the ability of the provider to cost-effectively reach a critical mass of clients with systems of delivery, market responsiveness, risk management and control that can generate a profit to the institution. Typically, this profit is ploughed back to ensure the long-term survival of the institution, i.e. the continuous provision of services demanded by its clients. The two long-term goals of microfinance are thus substantial outreach and sustainability. This article focus on microfinance services practices in Nepal on the basis of opinion survey.The Journal of Nepalese Business Studies Vol. Vii, No. 1, 2010-2011Page : 1-16Uploaded date: July 7, 2012

scholarly journals Identification and molecular characterization of SIV Vpr R50G mutation associated with long term survival in SIV-infected morphine dependent and control macaques

Virology ◽  
2013 ◽  
Vol 446 (1-2) ◽  
pp. 144-151 ◽  
Author(s):  
Ivelisse Rivera ◽  
Yashira García ◽  
Mohitkumar R. Gangwani ◽  
Richard J. Noel ◽  
Lucianette Maldonado ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Term Survival ◽  
Long Term Survival ◽  
And Control

Effect of using the doubly labelled water technique on long-term recapture in the brown long-eared bat (Plecotus auritus)

1994 ◽  
Vol 72 (4) ◽  
pp. 783-785
Author(s):  
A. C. Entwistle ◽  
J. R. Speakman ◽  
P. A. Racey
Keyword(s):  
Blood Sample ◽  
Control Groups ◽  
Doubly Labelled Water ◽  
Term Survival ◽  
Long Term Survival ◽  
And Control ◽  
Banding Study ◽  
Initial Capture

A banding study of Plecotus auritus was carried out in northeast Scotland between 1978 and 1991. A total of 526 bats were caught, and of these 211 had the procedures involved in the doubly labelled water technique performed on them (injection with isotopes, and in most cases removal of a small blood sample from the interfemoral vein). Recaptures of these bats in subsequent years allowed a direct comparison to be made between the proportions of recaptured bats which had been injected, those which had been both injected and bled, and those which had had neither procedure performed on them. The proportion of bats recaptured did not differ between the test and control groups, which suggests that these procedures had little or no effect on the long-term survival of this species, over and above any effect of the initial capture and handling.

scholarly journals Modelling the impact and control of an infectious disease in a plant nursery with infected plant material inputs

2016 ◽  
Vol 334 ◽  
pp. 27-43 ◽  
Author(s):  
Andrew M. Bate ◽  
Glyn Jones ◽  
Adam Kleczkowski ◽  
Alan MacLeod ◽  
Rebecca Naylor ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Plant Material ◽  
Infected Plant ◽  
Plant Nursery ◽  
And Control ◽  
The Impact ◽  
Infected Plant Material

scholarly journals First report of leaf blight caused by Phytophthora ramorum on cherry laurel (Prunus laurocerasus) in Washington State, USA.

Plant Disease ◽  
2020 ◽  
Author(s):  
Marianne Elliott ◽  
Lucy Rollins ◽  
Tyler Bourret ◽  
Gary Chastagner
Keyword(s):  
The United States ◽  
Washington State ◽  
Phytophthora Ramorum ◽  
Sterile Water ◽  
Long Distance ◽  
First Report ◽  
Plant Nursery ◽  
Cherry Laurel ◽  
Zoospore Suspension ◽  
Prunus Laurocerasus

In April 2014, Phytophthora ramorum (Werres, De Cock & Man in't Veld) was recovered from symptomatic foliage of cherry laurel (Prunus laurocerasus) at an ornamental plant nursery in Washington State. Cherry laurel, also known as English laurel, is widely propagated in WA because it is commonly used in landscaping. It is invasive in forests near the urban/wildland interface in the western US and in Europe (Rusterholz et al. 2018). Given its popularity as an ornamental species, the potential of this host to spread P. ramorum is of regulatory concern due to possible long distance spread to other states via nursery stock. Foliar symptoms consisted of dark brown lesions near wounds or around leaf margins where water collected. Shot-hole symptoms characterized by abscission zones and dropping of infected tissues were also observed. Lesions expanded beyond the margin of the shot-hole in some cases (Figure S1A). Phytophthora was isolated from symptomatic foliage by surface-sterilizing leaf pieces in 0.6% sodium hypochlorite and 2 rinses in sterile water. They were plated on PARP medium (Ferguson and Jeffers 1999). After 2-3 days, a slow-growing dense colony with coralloid hyphae was isolated onto V8 agar. P. ramorum was identified by observing morphological features (Figure S1B). Colony and spore morphology matched that of P. ramorum (Werres et al. 2001). The isolate was confirmed as P. ramorum by PCR and sequencing of ITS and COX1 regions using primers ITS1/ITS4 (White et al. 1990) and COX1F1/COX1R1 (Van Poucke et al. 2012). Sequences were submitted to GenBank (accession nos. ITS MT031969, COX1 MT031968). BLAST results showed at least 99% similarity with sequences of P. ramorum (ITS, KJ755124 [100%]; COX1, EU124926 [99%]). Multilocus genotyping with microsatellite markers placed the isolate in the EU1 clonal lineage. Pathogenicity of P. ramorum on cherry laurel was confirmed by completing Koch's Postulates using the isolate taken from this host. Two trials were done in a biocontainment chamber (USDA-APHIS permit # 65857) since P. ramorum is a quarantine pathogen and greenhouse trials could not be conducted, using detached stems from mature, visibly healthy cherry laurel plants growing in a landscape. Phytophthora ramorum inoculum was grown on V8A plates at 20®C for 2 weeks until sporangia were abundant. A zoospore suspension was produced by flooding plates with 7 ml sterile water, incubating for 2 hours at 5®C, then 1 hour at 24®C. Zoospores were observed with light microscopy, quantified with a hemocytometer and diluted to 1 x 104 zoospores/ml. A 10 µl droplet was placed at 3 wounded and 3 unwounded sites on 4 leaves per branch. In addition, a set of samples was inoculated by dipping foliage into the zoospore suspension for 30 seconds. A set of controls was mock inoculated using sterile water. Four branches per inoculation treatment were used and the trial was repeated once. Inoculated plant materials were incubated in moist chambers for 3-5 days at 20®C. Free moisture was present on foliage upon removal. Symptom development was assessed after incubation in the biocontainment chamber at 20®C for 7 days (Figure S1C). Phytophthora ramorum was reisolated from symptomatic tissue and the recovered culture was verified morphologically and by PCR and sequencing. It was isolated more often from foliage dipped in zoospore suspension than droplet inoculated, and more from wounded than unwounded sites. None of the water-inoculated controls were positive for P. ramorum. The presence of P. ramorum was also confirmed with DNA extraction from surface-sterilized symptomatic foliage followed by PCR and sequencing of the COX1 gene (EU124926, 100%) (Figure S2). To our knowledge, this is the first report of P. ramorum naturally infecting cherry laurel in the United States. Acknowledgements This work was supported by the USDA National Institute of Food and Agriculture, McIntire-Stennis project 1019284 and USDA APHIS Cooperative Agreement AP17PPQS&T00C070 Literature cited Ferguson and Jeffers, 1999. Plant Disease 83:1129-1136 Van Poucke, K. et al. 2012. Fungal Biology 116: 1178-1191. http://dx.doi.org/10.1016/j.funbio.2012.09.003 Werres, S. et al. 2001. Mycol. Res. 105:1155-1165. White, T. J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA.

scholarly journals Vaccine nationalism and the dynamics and control of SARS-CoV-2

Science ◽  
2021 ◽  
pp. e
Author(s):  
Caroline E. Wagner ◽  
Chadi M. Saad-Roy ◽  
Sinead E. Morris ◽  
Rachel E. Baker ◽  
Michael J. Mina ◽  
...  
Keyword(s):  
Natural Immunity ◽  
Economic Costs ◽  
Evolutionary Potential ◽  
Novel Variants ◽  
Dynamics And Control ◽  
Antigenic Evolution ◽  
Vaccine Distribution ◽  
Vaccine Availability ◽  
And Control ◽  
Epidemiological Characteristics

Vaccines provide powerful tools to mitigate the enormous public health and economic costs that the ongoing SARS-CoV-2 pandemic continues to exert globally, yet vaccine distribution remains unequal among countries. To examine the potential epidemiological and evolutionary impacts of ‘vaccine nationalism’, we extend previous models to include simple scenarios of stockpiling between two regions. In general, when vaccines are widely available and the immunity they confer is robust, sharing doses minimizes total cases across regions. A number of subtleties arise when the populations and transmission rates in each region differ, depending on evolutionary assumptions and vaccine availability. When the waning of natural immunity contributes most to evolutionary potential, sustained transmission in low access regions results in an increased potential for antigenic evolution, which may result in the emergence of novel variants that affect epidemiological characteristics globally. Overall, our results stress the importance of rapid equitable vaccine distribution for global control of the pandemic.

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