Chitosan application improves resistance to Fusarium circinatum in Pinus patula

Fusarium circinatum is the causal agent for the disease, pitch canker, in Pinus patula. Commercial forestry incurs large economic losses from the pathogen, primarily as a result of post-planting mortality resulting in increased re-establishment costs. One means of enhancing defense is through pretreatment of seedlings with chemicals or biologically derived compounds that stimulate defense responses; a process collectively known as induced resistance. We compared the efficiency of ten inducers in improving defense against F. circinatum in P. patula seedlings. Chitosan (10 mg/ml)was effective in reducing and delaying disease symptoms of pitch canker in seedlings. Under both nursery and greenhouse conditions, chitosan application resulted in reduced lesion lengths in treated plants compared to non-treated plants over a period of six weeks (pb0.05, Kruskal–Wallis). Reverse transcription-quantitative PCR expression analysis revealed that the reduction in lesion size in treated seedlings was accompanied by a four-fold increase in transcript abundance of the phenylalanine ammonia lyase transcript, which encodes an enzyme involved in the first committed step of the phenylpropanoid pathway. We suggest that the application of chitosan as part of an integrated management strategy, be further investigated for an effective approach to induce resistance in P. patula seedlings against F. circinatum.National Research Foundation (NRF) South Africa, and Mondi Business Paper and Sappi Forestry.http://www.elsevier.com/locate/sajbhb201

Out of sight, out of mind: long-term outcomes for people discharged home, to inpatient rehabilitation and to residential aged care after stroke

OnlinePubl.Purpose: The aim of this study was to describe differences in long-term outcomes for patients discharged to inpatient rehabilitation facilities (IRFs) following stroke compared to patients discharged directly home or to residential aged care facilities (RACFs). Materials and Methods: Cohort study. Data from the Australian Stroke Clinical Registry were linked to hospital admissions records and the national death index. Main outcomes: death and hospital readmissions up to 12 months post-admission, Health-related Quality of Life (HRQoL) 90-180 days post-admission. Results: Of 8,555 included patients (median age 75, 55% male, 83% ischemic stroke), 4,405 (51.5%) were discharged home, 3,442 (40.2%) to IRFs, and 708 (8.3%) to RACFs. No between-group differences were observed in hazard of death between patients discharged to IRFs versus home. Fewer patients discharged to IRFs were readmitted to hospital within 90, 180 or 365-days compared to patients discharged home (adjusted subhazard ratio [aSHR]:90-days 0.54, 95%CI 0.49, 0.61; aSHR:180-days 0.74, 95%CI 0.67, 0.82; aSHR:365-days 0.85, 95%CI 0.78, 0.93). Fewer patients discharged to IRFs reported problems with mobility compared to those discharged home (adjusted OR 0.54, 95%CI 0.47, 0.63), or to RACFs (aOR 0.35, 95%CI 0.25, 0.48). Overall HRQoL between 90-180 days was worse for people discharged to IRFs versus those discharged home and better than those discharged to RACFs. Conclusions: Several long-term outcomes differed significantly for patients discharged to different settings after stroke. Patients discharged to IRFs reported some better outcomes than people discharge directly home despite having markers of more severe stroke. Implications for rehabilitation: People with mild strokes are usually discharged directly home, people with moderate severity strokes to inpatient rehabilitation, and people with very severe strokes are usually discharged to residential aged care facilities. People discharged to inpatient rehabilitation reported fewer problems with mobility and had a reduced risk of hospital readmission in the first year post-stroke compared to people discharged directly home after stroke. The median self-reported health-related quality of life for people discharged to residential aged care equated to 'worst health state imaginable'.Elizabeth A. Lynch, Angela S. Labberton, Joosup Kim, Monique F. Kilkenny, Nadine E. Andrew, Natasha A. Lannin, Rohan Grimley, Steven G. Faux and Dominique A. Cadilhac; on behalf of the Stroke123 Investigators and AuSCR Consortiu

AXES at TRECVid 2011

Abstract The AXES project participated in the interactive known-item search task (KIS) and the interactive instance search task (INS) for TRECVid 2011. We used the same system architecture and a nearly identical user interface for both the KIS and INS tasks. Both systems made use of text search on ASR, visual concept detectors, and visual similarity search. The user experiments were carried out with media professionals and media students at the Netherlands Institute for Sound and Vision, with media professionals performing the KIS task and media students participating in the INS task. This paper describes the results and findings of our experiments

Quantum Oscillation Studies of the Fermi Surface of LaFePO

We review recent experimental measurements of the Fermi surface of the iron-pnictide superconductor LaFePO using quantum oscillation techniques. These studies show that the Fermi surface topology is close to that predicted by first principles density functional theory calculations, consisting of quasi-two-dimensional electron-like and hole-like sheets. The total volume of the two hole sheets is almost equal to that of the two electron sheets, and the hole and electron Fermi surface sheets are close to a nesting condition. No evidence for the predicted three dimensional pocket arising from the Fe $d_{z^2}$ band is found. Measurements of the effective mass suggest a renormalisation of around two, close to the value for the overall band renormalisation found in recent angle resolved photoemission measurements.Comment: Submitted to Physica C special issue on iron-pnictide superconductor

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Objectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.Results:Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.Conclusions:The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss

Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium.

Background The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings Significant dose–response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5–9 years to 89%quit_for_≥ 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects. Interpretation This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study. Abbreviations COPD, chronic obstructive pulmonary disease; CPG, cigarettes per day; ILCCO, International Lung Cancer Consortium; MeSH, medical subject headings; NSCLC, non-small cell lung cancer; OR, odds ratio; SCLC, small cell lung cancer

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification

Background Although polygenic risk score (PRS) has emerged as a promising tool for predicting cancer risk from genome-wide association studies (GWAS), the individual-level accuracy of lung cancer PRS and the extent to which its impact on subsequent clinical applications remains largely unexplored. Methods Lung cancer PRSs and confidence/credible interval (CI) were constructed using two statistical approaches for each individual: (1) the weighted sum of 16 GWAS-derived significant SNP loci and the CI through the bootstrapping method (PRS-16-CV) and (2) LDpred2 and the CI through posteriors sampling (PRS-Bayes), among 17,166 lung cancer cases and 12,894 controls with European ancestry from the International Lung Cancer Consortium. Individuals were classified into different genetic risk subgroups based on the relationship between their own PRS mean/PRS CI and the population level threshold. Results Considerable variances in PRS point estimates at the individual level were observed for both methods, with an average standard deviation (s.d.) of 0.12 for PRS-16-CV and a much larger s.d. of 0.88 for PRS-Bayes. Using PRS-16-CV, only 25.0% of individuals with PRS point estimates in the lowest decile of PRS and 16.8% in the highest decile have their entire 95% CI fully contained in the lowest and highest decile, respectively, while PRS-Bayes was unable to find any eligible individuals. Only 19% of the individuals were concordantly identified as having high genetic risk (> 90th percentile) using the two PRS estimators. An increased relative risk of lung cancer comparing the highest PRS percentile to the lowest was observed when taking the CI into account (OR = 2.73, 95% CI: 2.12–3.50, P-value = 4.13 × 10−15) compared to using PRS-16-CV mean (OR = 2.23, 95% CI: 1.99–2.49, P-value = 5.70 × 10−46). Improved risk prediction performance with higher AUC was consistently observed in individuals identified by PRS-16-CV CI, and the best performance was achieved by incorporating age, gender, and detailed smoking pack-years (AUC: 0.73, 95% CI = 0.72–0.74). Conclusions Lung cancer PRS estimates using different methods have modest correlations at the individual level, highlighting the importance of considering individual-level uncertainty when evaluating the practical utility of PRS

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Iam hiQ—a novel pair of accuracy indices for imputed genotypes

Background Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand. Results Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2). Conclusion We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data