The Effect of Vestibular Stimulation on Eye-Hand Coordination and Postural Control in Elite Basketball Players

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Protective efficacy against pandemic influenza of seasonal influenza vaccination in children in Hong Kong: a randomized controlled trial

BACKGROUND: The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear. METHODS: One child aged 6-17 years in each of 796 households was randomized to receive 2009-2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a >/=4-fold rise in serum antibody titer measured by hemagglutination inhibition assay. RESULTS: Receipt of TIV led to 8-13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval [CI], 31%-83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%-67%). CONCLUSIONS: Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051.postprin

A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)

Background: In order to facilitate implementation of precision medicine in clinical management of cancer, there is a need to harmonise and standardise the reporting and interpretation of clinically relevant genomics data. / Methods: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to propose a classification system for molecular aberrations based on the evidence available supporting their value as clinical targets. A group of experts from several institutions was assembled to review available evidence, reach a consensus on grading criteria and present a classification system. This was then reviewed, amended and finally approved by the ESMO TR and PM WG and the ESMO leadership. / Results: This first version of the ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) defines six levels of clinical evidence for molecular targets according to the implications for patient management: tier I, targets ready for implementation in routine clinical decisions; tier II, investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed; tier III, clinical benefit previously demonstrated in other tumour types or for similar molecular targets; tier IV, preclinical evidence of actionability; tier V, evidence supporting co-targeting approaches; and tier X, lack of evidence for actionability. / Conclusions: The ESCAT defines clinical evidence-based criteria to prioritise genomic alterations as markers to select patients for targeted therapies. This classification system aims to offer a common language for all the relevant stakeholders in cancer medicine and drug development

Efficacy of seasonal influenza vaccination in children in Hong Kong: a randomized controlled trial

Oral Presentation: abstract no. VII-1BACKGROUND: Seasonal influenza vaccination is most effective in preventing influenza infection and disease in healthy school-age children when circulating strains are similar to those included in the vaccine. The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear…postprintThe 14th International Symposium on Respiratory Viral Infections, Istanbul, Turkey, 23-26 March 2012

Recurrent hotspot mutations in HRAS Q61 and PI3K-AKT pathway genes as drivers of breast adenomyoepitheliomas

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, of which a subset will progress to invasive or metastatic cancer. We sought to define the genomic landscape of adenomyoepitheliomas. Massively parallel sequencing revealed highly recurrent somatic mutations in HRAS and PI3K-AKT pathway-related genes. Strikingly, HRAS mutations were restricted to estrogen receptor (ER)-negative tumors, all affected codon 61, and all but one co-occurred with PIK3CA or PIK3R1 mutations. To interrogate the functional significance of HRAS Q61 mutations in adenomyoepithelial differentiation, we expressed HRASQ61R alone or in combination with PIK3CAH1047R in non-transformed ER-negative breast epithelial cells. HRASQ61R induced characteristic phenotypes of adenomyoepitheliomas such as the expression of myoepithelial markers and loss of e-cadherin, hyperactivation of AKT signaling, and transformative properties that were arrested by combination therapy with AKT and MEK inhibitors. Our results indicate that breast adenomyoepitheliomas often manifest a unique transformation program featuring HRAS activation

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. Methods and Findings: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts. Our analysis revealed that mutations in the AR- and FOXA1-regulated networks, in which BRCA1 plays a key role, are associated with significantly higher sensitivity to ACT chemotherapy in the MDACC cohort (pCR rate of 94.1% compared to 16.6% in tumors without mutations in AR/FOXA1 pathway, adjusted p = 0.02) and significantly better survival outcome in the TCGA TNBC cohort (log-rank test, p = 0.05). Combined analysis of DNA sequencing, DNA methylation, and RNA sequencing identified tumors of a distinct BRCA-deficient (BRCA-D) TNBC subtype characterized by low levels of wild-type BRCA1/2 expression. Patients with functionally BRCA-D tumors had significantly better survival with standard-of-care chemotherapy than patients whose tumors were not BRCA-D (log-rank test, p = 0.021), and they had significantly higher mutation burden (p < 0.001) and presented clonal neoantigens that were associated with increased immune cell activity. A transcriptional signature of BRCA-D TNBC tumors was independently validated to be significantly associated with improved survival in the METABRIC dataset (log-rank test, p = 0.009). As a retrospective study, limitations include the small size and potential selection bias in the discovery cohort. Conclusions: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. © 2016 Jiang et al

Are we working towards global research priorities for management and conservation of sea turtles?

This is the final version. Available from Inter Research via the DOI in this recordThere is another ORE record for this publication: http://hdl.handle.net/10871/24817In 2010, an international group of 35 sea turtle researchers refined an initial list of more than 200 research questions into 20 metaquestions that were considered key for management and conservation of sea turtles. These were classified under 5 categories: reproductive biology, biogeography, population ecology, threats and conservation strategies. To obtain a picture of how research is being focused towards these key questions, we undertook a systematic review of the peer-reviewed literature (2014 and 2015) attributing papers to the original 20 questions. In total, we reviewed 605 articles in full and from these 355 (59%) were judged to substantively address the 20 key questions, with others focusing on basic science and monitoring that may lead to innovations or inform subsequent interpretation of effectiveness of conservation interventions and/or severity of threats. Progress to answering the 20 questions was not uniform and there were biases regarding focal turtle species, geographic scope and publication outlet. Whilst it offers some meaningful indications as to effort, quantifying peer-reviewed literature output is obviously not the only, and possibly not the best, metric for understanding research progress towards informing key conservation and management goals. Along with the literature review, an international group based on the original project consortium, with additional members, were assigned in groups of two or three (based on core expertise) to critically summarise recent progress towards answering each of the 20 questions. We found that significant research is being expended towards global priorities for management and conservation of sea turtles. Although highly variable, there has been significant progress in all the key questions identified in 2010. Undertaking this critical review has highlighted that it may be timely to undertake one or more new prioritizing exercises. For this to have maximal benefit we make a range of recommendations for its execution. These include a far greater engagement with social sciences, widening the pool of contributors and focussing the questions, perhaps disaggregating ecology and conservation.K.R.W-S is supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-125252

Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers

WOS: 000390900700001PubMed ID: 27903276Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.European CommissionEuropean Commission Joint Research Centre [658170]This work was funded by the European Commission H2020 Marie Sklodowska Curie Action Individual Fellowship (H2020-MSCA-IF, 658170) to CS and Breast Cancer Now to JMD and AHS