Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

BACKGROUND: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. METHODS: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. RESULTS: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). CONCLUSION: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance

International time trends in sudden unexpected infant death, 1969–2012

Background: Sudden unexpected infant death (SUID) - including sudden infant death syndrome (SIDS) - continues to be a major contributor to infant mortality worldwide. Our objective was to analyse time trends and to identify country-clusters. Methods: The National Statistical Offices of 52 countries provided the number of deaths and live births (1969-2012). We calculated infant mortality rates per 1000 live births for SUID, SIDS, and all-cause mortality. Overall, 29 countries provided sufficient data for time course analyses of SUID. To sensitively model change over time, we smoothed the curves of mortality rates (1980-2010). We performed a hierarchical cluster analysis to identify clusters of time trends for SUID and SIDS, including all-cause infant mortality. Results: All-cause infant mortality declined from 28.5 to 4.8 per 1000 live births (mean 12.4; 95% confidence interval 12.0-12.9) between 1969 and 2012. The cluster analysis revealed four country-clusters. Clusters 1 and 2 mostly contained countries showing the typical peak of SUID mortality during the 1980s. Cluster 1 had higher SUID mortality compared to cluster 2. All-cause infant mortality was low in both clusters but higher in cluster 1 compared to cluster 2. Clusters 3 and 4 had low rates of SUID without a peak during the 1980s. Cluster 3 had the highest all-cause infant mortality of all clusters. Cluster 4 had an intermediate all-cause infant mortality. The time trends of SUID and SIDS mortality were similar. Conclusions: The country-specific time trends in SUID varied considerably. The identification of country-clusters may promote research into how changes in sleep position, smoking, immunisation, or other factors are related to our findings

Explorations, Vol. 4, No. 1

Articles include: Cover: Old Yarmouth Light, 1960, Cape Forchu, Nova Scotia. By and from the collection of Edgar McKay. The Borderlands Concept: a new look at U.S.-Canada relations, by Victor Konrad and Lauren McKensey Fundy Tidal Power Project, by Gregory White Canadian Poet: Ken Norris Native American Life and Art: a celebration, November, 1986, by Lee-Ann Konrad The Montreal Canadiens: a cultural institution, by James J. Herlan U.S. and Canadian Executives: uses of formal and informal plans in top executive decision-making, by Kent Carter Our Cover Artist: bits and pieces of one man\u27s Nova Scotia, by Edgar McKay The Canadian-American Center and the Canadian Collection of the Fogler Library, by Alice Stewart Capitalist Development in the New England-Atlantic Provinces Region, by Robert H. Babcock Atlantic Canadian Members of Parliament as Representatives, by Howard Cody The Rower and the Pyramid: a tribute to Joe Walsh, by Edward D. Ives The Canadian-American Center: exercise in excellence, by Rand Erb Canadian and Maine Potatoes: a bushel of questions, by George K. Griner, Alan S. Kezis, and James D. Leiby After 20: the Future of the Canadian-American Center, by Victor Konra

Synthesis and properties of ZnTe and ZnTe/ZnS core/shell semiconductor nanocrystals

Nanocrystals obtained by growing a protecting ZnS shell onto a photoactive ZnTe core afford nanocrystals that can represent alternatives to cadmium-based quantum dots

Increasing efficiency of preclinical research by group sequential designs.

Despite the potential benefits of sequential designs, studies evaluating treatments or experimental manipulations in preclinical experimental biomedicine almost exclusively use classical block designs. Our aim with this article is to bring the existing methodology of group sequential designs to the attention of researchers in the preclinical field and to clearly illustrate its potential utility. Group sequential designs can offer higher efficiency than traditional methods and are increasingly used in clinical trials. Using simulation of data, we demonstrate that group sequential designs have the potential to improve the efficiency of experimental studies, even when sample sizes are very small, as is currently prevalent in preclinical experimental biomedicine. When simulating data with a large effect size of d = 1 and a sample size of n = 18 per group, sequential frequentist analysis consumes in the long run only around 80% of the planned number of experimental units. In larger trials (n = 36 per group), additional stopping rules for futility lead to the saving of resources of up to 30% compared to block designs. We argue that these savings should be invested to increase sample sizes and hence power, since the currently underpowered experiments in preclinical biomedicine are a major threat to the value and predictiveness in this research domain.German Federal Ministry of Education and Research (BMBF) www.bmbf.de (grant number 01EO1301)

Helmholtz Open Science Workshop „Zugang zu und Nachnutzung von wissenschaftlicher Software“ #hgfos16, Report; November 2016

Der Report des Helmholtz Open Science Workshops „Zugang zu und Nachnutzung von wissenschaftlicher Software“ #hgfos16 behandelt die Themen Standards und Qualitätssicherung; Reproduzierbarkeit; Lizenzierung und weitere rechtliche Aspekte; Zitation und Anerkennung; Sichtbarkeit und Modularität; Geschäftsmodelle; Personal, Ausbildung, Karrierewege. Diese Themen sind eng miteinander verzahnt. Für jeden Themenbereich werden jeweils die Relevanz, Fragestellungen, Herausforderungen, mögliche Lösungsansätze und Handlungsempfehlungen betrachtet

Jet coherence in QCD media: the antenna radiation spectrum

We study the radiation of a highly energetic partonic antenna in a colored state traversing a dense QCD medium. Resumming multiple scatterings of all involved constituents with the medium we derive the general gluon spectrum which encompasses both longitudinal color coherence between scattering centers in the medium, responsible for the well known Landau-Pomeranchuk-Migdal (LPM) effect, and transverse color coherence between partons inside a jet, leading, in vacuum, to angular ordering of the parton shower. We discuss shortly the onset of transverse decoherence which is reached in opaque media. In this regime, the spectrum consists of independent radiation off the antenna constituents.Comment: 15 pages, 2 figures, paper shortened and partly rewritten, references added, results unchange

Scientific Software – the role of best practices and recommendations

In Geosciences – like in most other communities – scientific work strongly depends on software. For big data analysis, existing (closed or open source) program packages are often mixed with newly developed codes. Different versions of software components and varying configurations can influence the result of data analysis. This often makes reproducibility of results and reuse of codes very difficult. Policies for publication and documentation of used and newly developed software, along with best practices, can help tackle this problem. Within the Helmholtz Association a Task Group “Access to and Re-use of scientific software” was implemented by the Open ScienceWorking Group in 2016. The aim of the Task Group is to foster the discussion about scientific software in the Open Science context and to formulate recommendations for the production and publication of scientific software, ensuring open access to it. As a first step, a workshop gathered interested scientists from institutions across Germany. The workshop brought together various existing initiatives from different scientific communities to analyse current problems, share established best practices and come up with possible solutions. The subjects in the working groups covered a broad range of themes, including technical infrastructures, standards and quality assurance, citation of software and reproducibility. Initial recommendations are presented and discussed in the talk. They are the foundation for further discussions in the Helmholtz Association and the Priority Initiative “Digital Information” of the Alliance of Science Organisations in Germany. The talk aims to inform about the activities and to link with other initiatives on the national or international level

Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress

International audience; High content omic techniques in combination with stable human in vitro cell culture systems have the potential to improve on current pre-clinical safety regimes by providing detailed mechanistic information of altered cellular processes. Here we investigated the added benefit of integrating transcriptomics, proteomics and metabolomics together with pharmacokinetics for drug testing regimes. Cultured human renal epithelial cells (RPTEC/TERT1) were exposed to the nephrotoxin Cyclosporine A (CsA) at therapeutic and supratherapeutic concentrations for 14 days. CsA was quantified in supernatants and cellular lysates by LC-MS/MS for kinetic modeling. There was a rapid cellular uptake and accumulation of CsA, with a non-linear relationship between intracellular and applied concentrations. CsA at 15 µM induced mitochondrial disturbances and activation of the Nrf2-oxidative-damage and the unfolded protein-response pathways. All three omic streams provided complementary information, especially pertaining to Nrf2 and ATF4 activation. No stress induction was detected with 5 µM CsA; however, both concentrations resulted in a maximal secretion of cyclophilin B. The study demonstrates for the first time that CsA-induced stress is not directly linked to its primary pharmacology. In addition we demonstrate the power of integrated omics for the elucidation of signaling cascades brought about by compound induced cell stress