Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer ...type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.
Mechanical characterization of electrical steels in an attempt to predict component fatigue has drawn more and more attention to magneto-mechanical coupling in ferromagnetic materials. In this paper, ...experimental evidence on the magneto-mechanical coupling of a thin Fe-Ni50 sheet subject to multiaxial stress due to electromagnetic peening-induced residual stresses is presented. A comprehensive model of the stress-dependent magnetostriction is validated using the Jiles-Atherton-Sablik (JAS) model for scalar ferromagnetic hysteresis. The JAS parameters are determined from an optimization algorithm, and the dependence of the model accuracy regarding its own parametrization is analyzed. Good correlation of experimentation data with the JAS model was obtained upon careful optimization of the model parameters.
•The transient law of conservation of momentum approximates the siphon draining course.•Variables modifying the fluid head loss and falling height impact draining dynamics.•Six dimensionless ...variables characterize siphon draining for 10 and 16 mm diameters.•An empirical correlation can predict the draining duration for 10 and 16 mm diameters.
This study aims at analyzing the phenomenon of siphon draining occurring in drainback solar thermal systems. Although several experimental studies have been previously carried out, there is a lack of theoretical work in the literature. Since describing the draining process from a theoretical point of view should include complex phenomena as two-phase flow and stochastic events, a simpler representation is sought through dimensional analysis. The main physical parameters impacting the draining are at first identified with the equations of fluid mechanics before being individually assessed with experiments. The piping diameter, the type of fluid, the piping length, the drained volume of the circuit as well as the singular pressure losses are for this purpose varied throughout the experiments. A methodology for obtaining an empirical equation using dimensionless variables is finally developed, showing that the impact of all the studied parameters on the draining time could be accurately described for piping with an inner diameter of 10 and 16 mm.
► In Thailand, the continuous decrease in the size of rubber plantations has led to the general adoption of intensive tapping systems which may lead to low labour productivity. ► We characterize the ...behaviour of the hevea latex harvesting under the Double Cut Alternative tapping system (DCA) ► Over a period of 10 years, DCA increased cumulative rubber production by 9% compared to a single cut tapping system (S/2 d2) of equivalent intensity. ► Such research will lead to new advances in our knowledge of the physiology of the rubber tree, mainly at the trunk scale. ► As DCA is a new tapping system further research is required to optimize the use of the DCA strategy.
In Thailand, the continuous decrease in the size of rubber plantations has led to the general adoption of intensive tapping systems which may lead to over harvesting, high rates of tapping panel dryness (TPD), short life-cycles of the plantations, and low labour productivity. In Thailand, farmers use a half-spiral downward tapping system (S/2) or a one third-spiral (S/3) with a tapping frequency of once two days (d2) or more. To increase productivity, it is difficult to reduce tapping frequencies, even with ethylene stimulation, as this would result in days without work for tappers. The purpose of this study was to characterize the behaviour of the Hevea latex yield under the double cut alternative tapping system (DCA). The aim was ensure the long-term sustainability of latex yield by increasing the time required for latex regeneration between two tappings through splitting this high tapping intensity (100% or above) into two different tapping cuts tapped alternately (S/2 d47d7(t,t). Over a period of 10 years, compared to a single cut tapping system (S/2 d2) of equivalent intensity, DCA increased cumulative rubber production by 9%. Ability of the trees to produce more latex under DCA was related to the sucrose and inorganic phosphorus contents of the latex cells in each tapping panel. DCA produced metabolic activity more favourable to yield during the first 10 years of tapping. But DCA also resulted in higher TPD rates, a sign of a metabolic dysfunction of the productive bark. DCA is a new tapping system. Further research is required to optimize the use of the DCA strategy. Such research will lead to new advances in our knowledge of the physiology of the rubber tree, mainly at the trunk scale.
Patient education constitutes a relevant strategy to improve pain management. In the field of therapeutic patient education (TPE), we aimed 1) to assess pain impact in cancer patients, 2) to identify ...patients' educative needs in pain management, and 3) to refine research criteria for its future evaluation.
Pain intensity, relief and interference were assessed in 75 cancer patients with unbalanced background pain. Self-assessment questionnaire evaluated i) patients' pain management and ii) their knowledge and needs in TPE.
Most patients experienced pain for more than 6 months and 41.6% reported adequate pain relief. Understanding pain and pain management were major patients' preferences (>58%). Most patients declared they knew their pain treatments, but fewer than half of them were able to name them. However, education concerning pain treatment was considered as essential in <30% of patients. Almost all patients (97.1%) stated pain education as beneficial, with a preference for individualized sessions (41.2%). In addition, the assessment criteria for its future evaluation were refined.
Targeted population mainly concerned patients with persistent pain. Only half of patients reported pain relief despite antalgics. Patient education was declared as beneficial for almost all participants.
Tailoring a pain TPE on patients' needs has the potential to help them to optimally manage their pain daily.
Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, ...in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures.
Patients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated.
Sixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity.
The 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.
La radiochirurgie et la radiothérapie stéréotaxique sont le standard de traitement des métastases cérébrales lorsqu’elles sont peu nombreuses, de petite taille, chez les patients en bon état général et à la maladie extracérébrale contrôlée. Les métastases plus volumineuses sont souvent acceptées en stéréotaxie, tandis que les métastases hémorragiques restent plutôt contre-indiquées pour ce type de traitement. L’objectif de cette étude rétrospective était de rapporter les résultats obtenus par un schéma de fractionnement 6×6Gy utilisé dans notre centre pour les métastases hémorragiques, de plus de 15cm3 ou situées proches de structures à risque.
Les patients traités par ce schéma dans notre centre de 2012 à 2016 ont été inclus. Le caractère hémorragique était défini sur l’imagerie scanographique et IRM. L’efficacité et la tolérance ont été évaluées.
Soixante-deux patients atteints de 92 métastases (32 hémorragiques) ont été inclus. Le suivi médian était de 10,1 mois. Le taux de contrôle local à 1 an pour les métastases hémorragiques, les grosses métastases, et les métastases proches de structure à risque étaient respectivement de 90,7 %, 73 % et 86,7 %. Les taux correspondants de survie globale étaient de 61,2 %, 32 % et 37,8 %. Des complications hémorragiques ont été observées chez 5,3 % des patients (deux lésions hémorragiques avant le traitement). Un seul cas de toxicité aiguë de grade 3 a été observé, résolutif après traitement symptomatique.
Le Schéma 6×6Gy semble réalisable et plutôt efficace en traitement des métastases hémorragiques, ce qui reste à confirmer en prospectif.
The first genetic map for Hevea spp. (2n=36) is presented here. It is based on a F^sub 1^progeny of 106 individuals allowing the construction of a female, a male, and a synthetic map according to the ...pseudo-testcross strategy. Progeny were derived from an interspecific cross between PB260, a H. brasiliensis cultivated clone, and RO38, a H. brasiliensis×H. benthamiana interspecific hybrid clone. The disomic inheritance observed for all the codominant markers scattered on the 2n=36 chromosomes revealed that Hevea behaves as diploids. Homologous linkage groups between the two parental maps were merged using bridge loci. A total of 717 loci constituted the synthetic map, including 301 RFLPs, 388 AFLPs, 18 microsatellites, and 10 isozymes. The markers were assembled into 18 linkage groups, thus reflecting the basic chromosome number, and covered a total distance of 2144 cM. Nine markers were found to be unlinked. Segregation distortion was rare (1.4%). Average marker density was 1 per 3 cM. Comparison of the distance between loci in the parental maps revealed significantly less meiotic recombination in the interspecific hybrid male parent than in the female parent. Hevea origin and genome organisation are discussed.PUBLICATION ABSTRACT
Summary
What is known and objective
A randomized phase III study was designed to assess the efficacy and safety of second‐line platinum‐based chemotherapy with or without erlotinib in non‐small cell ...lung cancer (NSCLC) with EGFR‐activating mutation after secondary resistance to EGFR‐TKIs (epidermal growth factor receptor tyrosine kinase inhibitors).
Case summary
We report herein two of the first three patients who presented with major gastrointestinal toxicities in the experimental arm of the trial.
What is new and conclusion
Pending further data, it would seem safer to administer EGFR‐TKIs and chemotherapy sequentially rather than concomitantly.
Chronology of the events about two cases of gastrointestinal toxicity following concurrent administration of erlotinib and platinum‐based chemotherapy.
Genetic information is encoded by, but potentially not limited to, a four-letter alphabet. A variety of predominantly hydrophobic nucleobase analogues that form self-pairs in DNA have been examined ...as third base pair candidates. For example, the PICS self-pair is both stable in duplex DNA and synthesized by some wild-type polymerases with reasonable efficiency. These efforts to expand the genetic code are expected to be facilitated by optimizing both the unnatural nucleobase analogues and the polymerases that replicate them. Here, we report the use of an activity-based selection system to evolve a DNA polymerase that more efficiently replicates DNA containing the PICS self-pair. The selection system is based on the co-display on phage of DNA polymerase libraries and a DNA substrate containing the self-pair. Only polymerases that accept the unnatural substrate incorporate a biotin-dUTP to the attached primer and may then be isolated on a streptavidin solid support. A mutant of Sf polymerase, P2, was evolved which both inserts dPICSTP opposite dPICS in the template and extends the unnatural primer terminus by incorporation of the next correct natural dNTP, where the parental enzyme catalyzes neither step at detectable rates. P2 was found to be a triple mutant of Sf, with the mutations F598I, I614F, and Q489H. The evolved properties of P2, as well as the observed mutations, are consistent with an increased affinity for the DNA primer-template containing the self-pair.
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