The ALERT-B questionnaire: A screening tool for the detection of gastroenterological late effects after radiotherapy for prostate cancer

There is an increasing need to measure treatment-related side effects in normal tissues following cancer therapy. The ALERT-B (Assessment of Late Effects of RadioTherapy - Bowel) questionnaire is a screening tool that is composed of four items related specifically to bowel symptoms. Those patients that respond with a “yes” to any of these items are referred on to gastroenterologist in order to improve the long-term consequences of these side effects of radiological treatment. Here we wish to test the ability of this questionnaire to identify these subsequent gastroenterological complications by tracking prostate cancer patients that were positive with respect to ALERT-B. We also carry out receiver-operator curve (ROC) analysis for baseline data for an overall ALERT-B questionnaire score with respect to subscale data for the Gastrointestinal Symptom Rating Scale (GSRS) and the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. 84.4% and 95.7% of patients identified by the ALERT-B questionnaire demonstrated complications diagnosed at 6 and 12 months post-treatment, respectively. ROC curve analysis of baseline data showed that ALERT-B detected clinically relevant levels of side effects established at baseline by the GSRS diarrhoea subscale (AUC = 0.867, 95% CI = 0.795 to 0.926) and at the minimally important level of side effects for the EPIC bowel subscale (AUC = 0.765, 95% CI = 0.617 to 0.913). These results show that ALERT-B provides a simple and effective screening tool for identifying gastroenterological complications after treatment for prostate cancer

QTL associated with resistance to cassava brown streak and cassava mosaic diseases in a bi-parental cross of two Tanzanian farmer varieties, Namikonga and Albert

Article purchasedCassava production in Africa is compromised by cassava brown streak disease (CBSD) and cassava mosaic disease (CMD). To reduce costs and increase the precision of resistance breeding, a QTL study was conducted to identify molecular markers linked to resistance against these diseases. A bi-parental F1 mapping population was developed from a cross between the Tanzanian farmer varieties, Namikonga and Albert. A one-step genetic linkage map comprising 943 SNP markers and 18 linkage groups spanning 1776.2 cM was generated. Phenotypic data from 240 F1 progeny were obtained from two disease hotspots in Tanzania, over two successive seasons, 2013 and 2014. Two consistent QTLs linked to resistance to CBSD-induced root necrosis were identified in Namikonga on chromosomes II (qCBSDRNFc2Nm) and XI (qCBSDRNc11Nm) and a putative QTL on chromosome XVIII (qCBSDRNc18Nm). qCBSDRNFc2Nm was identified at Naliendele in both seasons. The same QTL was also associated with CBSD foliar resistance. qCBSDRNc11Nm was identified at Chambezi in both seasons, and was characterized by three peaks, spanning a distance of 253 kb. Twenty-seven genes were identified within this region including two LRR proteins and a signal recognition particle. In addition, two highly significant CMD resistance QTL (qCMDc12.1A and qCMDc12.2A) were detected in Albert, on chromosome 12. Both qCMDc12.1A and qCMDc12.2A lay within the range of markers reported earlier, defining the CMD2 locus. This is the first time that two loci have been identified within the CMD2 QTL, and in germplasm of apparent East African origin. Additional QTLs with minor effects on CBSD and CMD resistance were also identified

Cross-over behaviour in a communication network

We address the problem of message transfer in a communication network. The network consists of nodes and links, with the nodes lying on a two dimensional lattice. Each node has connections with its nearest neighbours, whereas some special nodes, which are designated as hubs, have connections to all the sites within a certain area of influence. The degree distribution for this network is bimodal in nature and has finite variance. The distribution of travel times between two sites situated at a fixed distance on this lattice shows fat fractal behaviour as a function of hub-density. If extra assortative connections are now introduced between the hubs so that each hub is connected to two or three other hubs, the distribution crosses over to power-law behaviour. Cross-over behaviour is also seen if end-to-end short cuts are introduced between hubs whose areas of influence overlap, but this is much milder in nature. In yet another information transmission process, namely, the spread of infection on the network with assortative connections, we again observed cross-over behaviour of another type, viz. from one power-law to another for the threshold values of disease transmission probability. Our results are relevant for the understanding of the role of network topology in information spread processes.Comment: 12 figure

Habitable Zones of Host Stars During the Post-MS Phase

A star will become brighter and brighter with stellar evolution, and the distance of its habitable zone will become farther and farther. Some planets outside the habitable zone of a host star during the main sequence phase may enter the habitable zone of the host star during other evolutionary phases. A terrestrial planet within the habitable zone of its host star is generally thought to be suited to life existence. Furthermore, a rocky moon around a giant planet may be also suited to life survive, provided that the planet-moon system is within the habitable zone of its host star. Using Eggleton's code and the boundary flux of habitable zone, we calculate the habitable zone of our Solar after the main sequence phase. It is found that Mars' orbit and Jupiter's orbit will enter the habitable zone of Solar during the subgiant branch phase and the red giant branch phase, respectively. And the orbit of Saturn will enter the habitable zone of Solar during the He-burning phase for about 137 million years. Life is unlikely at any time on Saturn, as it is a giant gaseous planet. However, Titan, the rocky moon of Saturn, may be suitable for biological evolution and become another Earth during that time. For low-mass stars, there are similar habitable zones during the He-burning phase as our Solar, because there are similar core masses and luminosities for these stars during that phase.Comment: 6 pages, 7 figures. Accepted by Ap & S

Neoadjuvant pazopanib and molecular analysis of tissue response in renal cell carcinoma

BACKGROUND. Surgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%–40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib. METHODS. ccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment. RESULTS. Twenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core profiles. However, a reduction in private mutations followed treatment, suggesting a selective process favoring enrichment of driver mutations. CONCLUSION. Neoadjuvant pazopanib is safe and active in ccRCC. Future genomic analyses may enable the segregation of driver and passenger mutations. Furthermore, tumor infiltrating immune cells persist during therapy, suggesting that pazopanib can be combined with immune checkpoint inhibitors without dampening the immune response. FUNDING. Support was provided by Novartis and GlaxoSmithKline as part of an investigator-initiated study

Sequencing wild and cultivated cassava and related species reveals extensive interspecific hybridization and genetic diversity

Cassava (Manihot esculenta) provides calories and nutrition for more than half a billion people. It was domesticated by native Amazonian peoples through cultivation of the wild progenitor M. esculenta ssp. flabellifolia and is now grown in tropical regions worldwide. Here we provide a high-quality genome assembly for cassava with improved contiguity, linkage, and completeness; almost 97% of genes are anchored to chromosomes. We find that paleotetraploidy in cassava is shared with the related rubber tree Hevea, providing a resource for comparative studies. We also sequence a global collection of 58 Manihot accessions, including cultivated and wild cassava accessions and related species such as Ceará or India rubber (M. glaziovii), and genotype 268 African cassava varieties. We find widespread interspecific admixture, and detect the genetic signature of past cassava breeding programs. As a clonally propagated crop, cassava is especially vulnerable to pathogens and abiotic stresses. This genomic resource will inform future genome-enabled breeding efforts to improve this staple crop

Candidate genes for field resistance to cassava brown streak disease revealed through the analysis of multiple data sources

Open Access JournalCassava (Manihot esculenta Crantz) is a food and industrial storage root crop with substantial potential to contribute to managing risk associated with climate change due to its inherent resilience and in providing a biodegradable option in manufacturing. In Africa, cassava production is challenged by two viral diseases, cassava brown streak disease (CBSD) and cassava mosaic disease. Here we detect quantitative trait loci (QTL) associated with CBSD in a biparental mapping population of a Tanzanian landrace, Nachinyaya and AR37-80, phenotyped in two locations over three years. The purpose was to use the information to ultimately facilitate either marker-assisted selection or adjust weightings in genomic selection to increase the efficiency of breeding. Results from this study were considered in relation to those from four other biparental populations, of similar genetic backgrounds, that were phenotyped and genotyped simultaneously. Further, we investigated the co-localization of QTL for CBSD resistance across populations and the genetic relationships of parents based on whole genome sequence information. Two QTL on chromosome 4 for resistance to CBSD foliar symptoms and one on each of chromosomes 11 and 18 for root necrosis were of interest. Of significance within the candidate genes underlying the QTL on chromosome 4 are Phenylalanine ammonia-lyase (PAL) and Cinnamoyl-CoA reductase (CCR) genes and three PEPR1-related kinases associated with the lignin pathway. In addition, a CCR gene was also underlying the root necrosis-resistant QTL on chromosome 11. Upregulation of key genes in the cassava lignification pathway from an earlier transcriptome study, including PAL and CCR, in a CBSD-resistant landrace compared to a susceptible landrace suggests a higher level of basal lignin deposition in the CBSD-resistant landrace. Earlier RNAscope® in situ hybridisation imaging experiments demonstrate that cassava brown streak virus (CBSV) is restricted to phloem vessels in CBSV-resistant varieties, and phloem unloading for replication in mesophyll cells is prevented. The results provide evidence for the involvement of the lignin pathway. In addition, five eukaryotic initiation factor (eIF) genes associated with plant virus resistance were found within the priority QTL regions

3D MHD Coronal Oscillations About a Magnetic Null Point: Application of WKB Theory

This paper is a demonstration of how the WKB approximation can be used to help solve the linearised 3D MHD equations. Using Charpit's Method and a Runge-Kutta numerical scheme, we have demonstrated this technique for a potential 3D magnetic null point, ${\bf{B}}=(x,\epsilon y -(\epsilon +1)z)$. Under our cold plasma assumption, we have considered two types of wave propagation: fast magnetoacoustic and Alfv\'en waves. We find that the fast magnetoacoustic wave experiences refraction towards the magnetic null point, and that the effect of this refraction depends upon the Alfv\'en speed profile. The wave, and thus the wave energy, accumulates at the null point. We have found that current build up is exponential and the exponent is dependent upon $\epsilon$. Thus, for the fast wave there is preferential heating at the null point. For the Alfv\'en wave, we find that the wave propagates along the fieldlines. For an Alfv\'en wave generated along the fan-plane, the wave accumulates along the spine. For an Alfv\'en wave generated across the spine, the value of $\epsilon$ determines where the wave accumulation will occur: fan-plane ($\epsilon=1$), along the $x-$axis ($0<\epsilon <1$) or along the $y-$axis ($\epsilon>1$). We have shown analytically that currents build up exponentially, leading to preferential heating in these areas. The work described here highlights the importance of understanding the magnetic topology of the coronal magnetic field for the location of wave heating.Comment: 26 pages, 12 figure

Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of $\sqrt{s_{\text{NN}}}=5$TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, $\Delta\eta$, and relative azimuthal angle, $\Delta\phi$, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, $\Delta\phi \approx 0$, is observed in the pseudorapidity range $2.0<\eta<4.9$. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to $\eta=4.9$. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

Study of the production of Λb0\Lambda_b^0 and B‾0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0→J/ψpK−\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

The product of the $\Lambda_b^0$ ($\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ ($\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\rm T}<20~{\rm GeV}/c$ and $2.0<y<4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\sqrt{s}=7~{\rm TeV}$ in 2011 and $\sqrt{s}=8~{\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\Lambda_B^0}/f_d$, the branching fraction of the decay $\Lambda_b^0\rightarrow J/\psi pK^-$ is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay $\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0$, and the fourth is due to the knowledge of $f_{\Lambda_b^0}/f_d$. The sum of the asymmetries in the production and decay between $\Lambda_b^0$ and $\overline{\Lambda}_b^0$ is also measured as a function of $p_{\rm T}$ and $y$. The previously published branching fraction of $\Lambda_b^0\rightarrow J/\psi p\pi^-$, relative to that of $\Lambda_b^0\rightarrow J/\psi pK^-$, is updated. The branching fractions of $\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^-$ are determined.Comment: 29 pages, 19figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm