The ability of the green peach aphid (Myzus persicae) to penetrate mesh crop covers used to protect potato crops against tomato potato psyllid (Bactericera cockerelli)

In Central and North America, Australia and New Zealand, potato (Solanum tuberosum) crops are attacked by Bactericera cockerelli, the tomato potato psyllid (TPP). 'Mesh crop covers' which are used in Europe and Israel to protect crops from insect pests, have been used experimentally in New Zealand for TPP control. While the covers have been effective for TPP management, the green peach aphid (GPA, Myzus persicae) has been found in large numbers under the mesh crop covers. This study investigated the ability of the GPA to penetrate different mesh hole sizes. Experiments using four sizes (0.15 × 0.15, 0.15 × 0.35, 0.3 × 0.3 and 0.6 × 0.6 mm) were carried out under laboratory conditions to investigate: (i) which mesh hole size provided the most effective barrier to GPA; (ii) which morph of adult aphids (apterous or alate) and/or their progeny could breach the mesh crop cover; (iii) would leaves touching the underside of the cover, as opposed to having a gap between leaf and the mesh, increase the number of aphids breaching the mesh; and (iv) could adults feed on leaves touching the cover by putting only their heads and/or stylets through it? No adult aphids, either alate or apterous, penetrated the mesh crop cover; only nymphs did this, the majority being the progeny of alate adults. Nymphs of the smaller alatae aphids penetrated the three coarsest mesh sizes; nymphs of the larger apterae penetrated the two coarsest sizes, but no nymphs penetrated the smallest mesh size. There was no statistical difference in the number of aphids breaching the mesh crop cover when the leaflets touched its underside compared to when there was a gap between leaf and mesh crop cover. Adults did not feed through the mesh crop cover, though they may have been able to sense the potato leaflet using visual and/or olfactory cues and produce nymphs as a result. As these covers are highly effective for managing TPP on field potatoes, modifications of this protocol are required to make it effective against aphids as well as TPP

Improving Ethical Review of Research Involving Incentives for Health Promotion

Alex London and colleagues propose new ethical frameworks for evaluating the risks associated with research in which financial or other incentives are used to promote healthy behavior

Incentive payments are not related to expected health gain in the pay for performance scheme for UK primary care: cross-sectional analysis

Background: The General Medical Services primary care contract for the United Kingdom financially rewards performance in 19 clinical areas, through the Quality and Outcomes Framework. Little is known about how best to determine the size of financial incentives in pay for performance schemes. Our aim was to test the hypothesis that performance indicators with larger population health benefits receive larger financial incentives. Methods: We performed cross sectional analyses to quantify associations between the size of financial incentives and expected health gain in the 2004 and 2006 versions of the Quality and Outcomes Framework. We used non-parametric two-sided Spearman rank correlation tests. Health gain was measured in expected lives saved in one year and in quality adjusted life years. For each quality indicator in an average sized general practice we tested for associations first, between the marginal increase in payment and the health gain resulting from a one percent point improvement in performance and second, between total payment and the health gain at the performance threshold for maximum payment. Results: Evidence for lives saved or quality adjusted life years gained was found for 28 indicators accounting for 41% of the total incentive payments. No statistically significant associations were found between the expected health gain and incentive gained from a marginal 1% increase in performance in either the 2004 or 2006 version of the Quality and Outcomes Framework. In addition no associations were found between the size of financial payment for achievement of an indicator and the expected health gain at the performance threshold for maximum payment measured in lives saved or quality adjusted life years. Conclusions: In this subgroup of indicators the financial incentives were not aligned to maximise health gain. This disconnection between incentive and expected health gain risks supporting clinical activities that are only marginally effective, at the expense of more effective activities receiving lower incentives. When designing pay for performance programmes decisions about the size of the financial incentive attached to an indicator should be informed by information on the health gain to be expected from that indicator

MicroRNA-224 Targets SMAD Family Member 4 to Promote Cell Proliferation and Negatively Influence Patient Survival

10.1371/journal.pone.0068744PLoS ONE87-POLN

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study

10.1038/sj.bjc.6601340British Journal of Cancer8991686-1692BJCA

Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.</p> <p>Methods</p> <p>We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Results</p> <p>We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity <it>in vitro</it>. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.</p> <p>Conclusions</p> <p>Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.</p

Small-molecule-induced DNA damage identifies alternative DNA structures in human genes.

Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show that the G-quadruplex-interacting drug pyridostatin promotes growth arrest in human cancer cells by inducing replication- and transcription-dependent DNA damage. A chromatin immunoprecipitation sequencing analysis of the DNA damage marker γH2AX provided the genome-wide distribution of pyridostatin-induced sites of damage and revealed that pyridostatin targets gene bodies containing clusters of sequences with a propensity for G-quadruplex formation. As a result, pyridostatin modulated the expression of these genes, including the proto-oncogene SRC. We observed that pyridostatin reduced SRC protein abundance and SRC-dependent cellular motility in human breast cancer cells, validating SRC as a target of this drug. Our unbiased approach to define genomic sites of action for a drug establishes a framework for discovering functional DNA-drug interactions

Clinical Ethics in Gabon: The Spectrum of Clinical Ethical Issues Based on Findings from In-Depth Interviews at Three Public Hospitals

Introduction Unlike issues in biomedical research ethics, ethical challenges arising in daily clinical care in Sub-Saharan African countries have not yet been studied in a systematic manner. However this has to be seen as a distinct entity as we argue in this paper. Our aim was to give an overview of the spectrum of clinical ethical issues and to understand what influences clinical ethics in the Sub-Saharan country of Gabon. Materials and Methods In-depth interviews with 18 health care professionals were conducted at three hospital sites in Gabon. Interview transcripts were analyzed using a grounded theory approach (open and axial coding),giving a qualitative spectrum of categories for clinical ethical issues. Validity was checked at a meeting with study participants and other health care experts in Gabon after analysis of the data. Results Twelve main categories (with 28 further-specified subcategories) for clinical ethical issues were identified and grouped under three core categories: A) micro level: "confidentiality and information","interpersonal, relational and behavioral issues","psychological strain of individuals",and "scarce resources";B) meso level: "structural issues of medical institutions","issues with private clinics","challenges connected to the family",and "issues of education, training and competence";and C) macro level: "influence of society, culture, religion and superstition","applicability of western medicine","structural issues on the political level",and "legal issues". Discussion Interviewees reported a broad spectrum of clinical ethical issues that go beyond challenges related to scarce financial and human resources. Specific socio-cultural, historical and educational backgrounds also played an important role. In fact these influences are central to an understanding of clinical ethics in the studied local context. Further research in the region is necessary to put our study into perspective. As many participants reported a lack of awareness of ethical issues amongst other health care professionals in daily clinical practice, we suggest that international organizations and national medical schools should consider infrastructure and tools to improve context-sensitive capacity building in clinical ethics for Sub-Saharan African countries like Gabon