Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non-small cell lung cancer (NSCLC): A feasibility study

Background: Concurrent chemoradiotherapy has improved survival in inoperable stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in order to establish a dose recommendation for oral vinorelbine in combination with cisplatin and simultaneous radiotherapy. Patients and Methods: Previously untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered at 3 different levels (40, 50 and 60 mg/m(2)). This was to be followed by 2 cycles of cisplatin/vinorelbine oral consolidation chemotherapy. The study goal was to determine the maximal recommended dose of oral vinorelbine during concurrent treatment. Results: 11 stage IIIB patients were entered into the study. The median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia, esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only toxicities. The overall response was 73%. Conclusion: Oral vinorelbine 50 mg/m(2) (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is the recommended dose in combination with radiotherapy (66 Gy) and will be used for concurrent chemoradiotherapy in a forthcoming phase III trial testing the efficacy of consolidation chemotherapy in patients not progressing after chemoradiotherapy

The Relationship Between HR Practices and Firm Performance: Examining Causal Order

Significant research attention has been devoted to examining the relationship between HR practices and firm performance, and the research support has assumed HR as the causal variable. Using data from 45 business units (with 62 data points), this study examines how measures of HR practices correlate with past, concurrent, and future operational performance measures. The results indicate that correlations with performance measures at all three times are both high and invariant, and that controlling for past or concurrent performance virtually eliminates the correlation of HR with future performance. Implications are discussed

Optical Trapping of an Ion

For several decades, ions have been trapped by radio frequency (RF) and neutral particles by optical fields. We implement the experimental proof-of-principle for trapping an ion in an optical dipole trap. While loading, initialization and final detection are performed in a RF trap, in between, this RF trap is completely disabled and substituted by the optical trap. The measured lifetime of milliseconds allows for hundreds of oscillations within the optical potential. It is mainly limited by heating due to photon scattering. In future experiments the lifetime may be increased by further detuning the laser and cooling the ion. We demonstrate the prerequisite to merge both trapping techniques in hybrid setups to the point of trapping ions and atoms in the same optical potential.Comment: 5 pages, 3 figure

A Note on Encodings of Phylogenetic Networks of Bounded Level

Driven by the need for better models that allow one to shed light into the question how life's diversity has evolved, phylogenetic networks have now joined phylogenetic trees in the center of phylogenetics research. Like phylogenetic trees, such networks canonically induce collections of phylogenetic trees, clusters, and triplets, respectively. Thus it is not surprising that many network approaches aim to reconstruct a phylogenetic network from such collections. Related to the well-studied perfect phylogeny problem, the following question is of fundamental importance in this context: When does one of the above collections encode (i.e. uniquely describe) the network that induces it? In this note, we present a complete answer to this question for the special case of a level-1 (phylogenetic) network by characterizing those level-1 networks for which an encoding in terms of one (or equivalently all) of the above collections exists. Given that this type of network forms the first layer of the rich hierarchy of level-k networks, k a non-negative integer, it is natural to wonder whether our arguments could be extended to members of that hierarchy for higher values for k. By giving examples, we show that this is not the case

Correlation-Adjusted Regression Survival Scores for High-Dimensional Variable Selection

Background The development of classification methods for personalized medicine is highly dependent on the identification of predictive genetic markers. In survival analysis it is often necessary to discriminate between influential and non-influential markers. It is common to perform univariate screening using Cox scores, which quantify the associations between survival and each of the markers to provide a ranking. Since Cox scores do not account for dependencies between the markers, their use is suboptimal in the presence highly correlated markers. Methods As an alternative to the Cox score, we propose the correlation-adjusted regression survival (CARS) score for right-censored survival outcomes. By removing the correlations between the markers, the CARS score quantifies the associations between the outcome and the set of “de-correlated” marker values. Estimation of the scores is based on inverse probability weighting, which is applied to log-transformed event times. For high-dimensional data, estimation is based on shrinkage techniques. Results The consistency of the CARS score is proven under mild regularity conditions. In simulations with high correlations, survival models based on CARS score rankings achieved higher areas under the precision-recall curve than competing methods. Two example applications on prostate and breast cancer confirmed these results. CARS scores are implemented in the R package carSurv. Conclusions In research applications involving high-dimensional genetic data, the use of CARS scores for marker selection is a favorable alternative to Cox scores even when correlations between covariates are low. Having a straightforward interpretation and low computational requirements, CARS scores are an easy-to-use screening tool in personalized medicine research.This research was supported by the Deutsche Forschungsgemeinschaft (Project SCHM 2966/1-2), Wellcome Trust and the Royal Society (Grant Number 204623/Z/16/Z) and the UK Medical Research Council (Grant Number MC_UU_00002/7

Sharp upturn of life expectancy in the Netherlands: effect of more health care for the elderly?

During the 1980s and 1990s life expectancy at birth has risen only slowly in the Netherlands. In 2002, however, the rise in life expectancy suddenly accelerated. We studied the possible causes of this remarkable development. Mortality data by age, gender and cause of death were analyzed using life table methods and age-period-cohort modeling. Trends in determinants of mortality (including health care delivery) were compared with trends in mortality. Two-thirds of the increase in life expectancy at birth since 2002 were due to declines in mortality among those aged 65 and over. Declines in mortality reflected a period rather than a cohort effect, and were seen for a wide range of causes of death. Favorable changes in mortality determinants coinciding with the acceleration of mortality decline were mainly seen within the health care system. Health care expenditure rose rapidly after 2001, and was accompanied by a sharp rise of specialist visits, drug prescriptions, hospital admissions and surgical procedures among the elderly. A decline of deaths following non-treatment decisions suggests a change towards more active treatment of elderly patients. Our findings are consistent with the idea that the sharp upturn of life expectancy in the Netherlands was at least partly due to a sharp increase in health care for the elderly, and has been facilitated by a relaxation of budgetary constraints in the health care system

Introduction to magnetic resonance methods in photosynthesis

Electron paramagnetic resonance (EPR) and, more recently, solid-state nuclear magnetic resonance (NMR) have been employed to study photosynthetic processes, primarily related to the light-induced charge separation. Information obtained on the electronic structure, the relative orientation of the cofactors, and the changes in structure during these reactions should help to understand the efficiency of light-induced charge separation. A short introduction to the observables derived from magnetic resonance experiments is given. The relation of these observables to the electronic structure is sketched using the nitroxide group of spin labels as a simple example

Flavour in supersymmetry: horizontal symmetries or wave function renormalisation

We compare theoretical and experimental predictions of two main classes of models addressing fermion mass hierarchies and flavour changing neutral currents (FCNC) effects in supersymmetry: Froggatt-Nielsen (FN) U(1) gauged flavour models and Nelson-Strassler/extra dimensional models with hierarchical wave functions for the families. We show that whereas the two lead to identical predictions in the fermion mass matrices, the second class generates a stronger suppression of FCNC effects. We prove that, whereas at first sight the FN setup is more constrained due to anomaly cancelation conditions, imposing unification of gauge couplings in the second setup generates conditions which precisely match the mixed anomaly constraints in the FN setup. Finally, we provide an economical extra dimensional realisation of the hierarchical wave functions scenario in which the leptonic FCNC can be efficiently suppressed due to the strong coupling (CFT) origin of the electron mass.Comment: 23 page

Soliton pair dynamics in patterned ferromagnetic ellipses

Confinement alters the energy landscape of nanoscale magnets, leading to the appearance of unusual magnetic states, such as vortices, for example. Many basic questions concerning dynamical and interaction effects remain unanswered, and nanomagnets are convenient model systems for studying these fundamental physical phenomena. A single vortex in restricted geometry, also known as a non-localized soliton, possesses a characteristic translational excitation mode that corresponds to spiral-like motion of the vortex core around its equilibrium position. Here, we investigate, by a microwave reflection technique, the dynamics of magnetic soliton pairs confined in lithographically defined, ferromagnetic Permalloy ellipses. Through a comparison with micromagnetic simulations, the observed strong resonances in the subgigahertz frequency range can be assigned to the translational modes of vortex pairs with parallel or antiparallel core polarizations. Vortex polarizations play a negligible role in the static interaction between two vortices, but their effect dominates the dynamics.Comment: supplemental movies on http://www.nature.com/nphys/journal/v1/n3/suppinfo/nphys173_S1.htm