Improving R&D productivity requires a balanced approach

In recent years pharmaceutical companies have implemented Operational Excellence (OpEx) in their R&D organizations to improve productivity but had only limited success. Practitioners and management start to question the effectiveness of process-focused improvement methodologies. In this article, we illustrate a number of challenges OpEx practitioners face and argue that our long-held assumptions and lack of understanding of pharmaceutical R&D can prevent us from seeing the real problems. We recommend a balanced approach by integrating process management with organization’s project management capability in order to better engage the stakeholders and deliver both short-term results and long-term improvement

Periodic orbit analysis of an elastodynamic resonator using shape deformation

We report the first definitive experimental observation of periodic orbits (POs) in the spectral properties of an elastodynamic system. The Fourier transform of the density of flexural modes show peaks that correspond to stable and unstable POs of a clover shaped quartz plate. We change the shape of the plate and find that the peaks corresponding to the POs that hit only the unperturbed sides are unchanged proving the correspondence. However, an exact match to the length of the main POs could be made only after a small rescaling of the experimental results. Statistical analysis of the level dynamics also shows the effect of the stable POs.Comment: submitted to Europhysics Letter

Whipworms in humans and pigs: origins and demography

© 2016 Hawash et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article.NHM Repositor

Distinct nature of static and dynamic magnetic stripes in cuprate superconductors

We present detailed neutron scattering studies of the static and dynamic stripes in an optimally doped high-temperature superconductor, La$_2$CuO$_{4+y}$. We find that the dynamic stripes do not disperse towards the static stripes in the limit of vanishing energy transfer. We conclude that the dynamic stripes observed in neutron scattering experiments are not the Goldstone modes associated with the broken symmetry of the simultaneously observed static stripes, but rather that the signals originate from different domains in the sample. These domains may be related by structural twinning, or may be entirely different phases, where the static stripes in one phase are pinned versions of the dynamic stripes in the other. Our results explain earlier observations of unusual dispersions in underdoped La$_{2-x}$Sr$_x$CuO$_{4}$ ($x=0.07$) and La$_{2-x}$Ba$_x$CuO$_{4}$ ($x=0.095$). Our findings are relevant for all compounds exhibiting magnetic stripes, and may thus be a vital part in unveiling the nature of high temperature superconductivity

Models and metaphors: complexity theory and through-life management in the built environment

Complexity thinking may have both modelling and metaphorical applications in the through-life management of the built environment. These two distinct approaches are examined and compared. In the first instance, some of the sources of complexity in the design, construction and maintenance of the built environment are identified. The metaphorical use of complexity in management thinking and its application in the built environment are briefly examined. This is followed by an exploration of modelling techniques relevant to built environment concerns. Non-linear and complex mathematical techniques such as fuzzy logic, cellular automata and attractors, may be applicable to their analysis. Existing software tools are identified and examples of successful built environment applications of complexity modelling are given. Some issues that arise include the definition of phenomena in a mathematically usable way, the functionality of available software and the possibility of going beyond representational modelling. Further questions arising from the application of complexity thinking are discussed, including the possibilities for confusion that arise from the use of metaphor. The metaphor of a 'commentary machine' is suggested as a possible way forward and it is suggested that an appropriate linguistic analysis can in certain situations reduce perceived complexity

Magnetic ground state and magnon-phonon interaction in multiferroic h-YMnO3_3

Inelastic neutron scattering has been used to study the magneto-elastic excitations in the multiferroic manganite hexagonal YMnO$_3$. An avoided crossing is found between magnon and phonon modes close to the Brillouin zone boundary in the $(a,b)$-plane. Neutron polarization analysis reveals that this mode has mixed magnon-phonon character. An external magnetic field along the $c$-axis is observed to cause a linear field-induced splitting of one of the spin wave branches. A theoretical description is performed, using a Heisenberg model of localized spins, acoustic phonon modes and a magneto-elastic coupling via the single-ion magnetostriction. The model quantitatively reproduces the dispersion and intensities of all modes in the full Brillouin zone, describes the observed magnon-phonon hybridized modes, and quantifies the magneto-elastic coupling. The combined information, including the field-induced magnon splitting, allows us to exclude several of the earlier proposed models and point to the correct magnetic ground state symmetry, and provides an effective dynamic model relevant for the multiferroic hexagonal manganites.Comment: 12 pages, 10 figure

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations

VINYL: The VIrtual Neutron and x-raY Laboratory and its applications

Experiments conducted in large scientific research infrastructures, such as synchrotrons, free electron lasers and neutron sources become increasingly complex. Such experiments, often investigating complex physical systems, are usually performed under strict time limitations and may depend critically on experimental parameters. To prepare and analyze these complex experiments, a virtual laboratory which provides start-to-end simulation tools can help experimenters predict experimental results under real or close to real instrument conditions. As a part of the PaNOSC (Photon and Neutron Open Science Cloud) project, the VIrtual Neutron and x-raY Laboratory (VINYL) is designed to be a cloud service framework to implement start-to-end simulations for those scientific facilities. In this paper, we present an introduction of the virtual laboratory framework and discuss its applications to the design and optimization of experiment setups as well as the estimation of experimental artifacts in an X-ray experiment

Level curvature distribution in a model of two uncoupled chaotic subsystems

We study distributions of eigenvalue curvatures for a block diagonal random matrix perturbed by a full random matrix. The most natural physical realization of this model is a quantum chaotic system with some inherent symmetry, such that its energy levels form two independent subsequences, subject to a generic perturbation which does not respect the symmetry. We describe analytically a crossover in the form of a curvature distribution with a tunable parameter namely the ratio of inter/intra subsystem coupling strengths. We find that the peak value of the curvature distribution is much more sensitive to the changes in this parameter than the power law tail behaviour. This observation may help to clarify some qualitative features of the curvature distributions observed experimentally in acoustic resonances of quartz blocks

Transport of a quantum degenerate heteronuclear Bose-Fermi mixture in a harmonic trap

We report on the transport of mixed quantum degenerate gases of bosonic 87Rb and fermionic 40K in a harmonic potential provided by a modified QUIC trap. The samples are transported over a distance of 6 mm to the geometric center of the anti-Helmholtz coils of the QUIC trap. This transport mechanism was implemented by a small modification of the QUIC trap and is free of losses and heating. It allows all experiments using QUIC traps to use the highly homogeneous magnetic fields that can be created in the center of a QUIC trap and improves the optical access to the atoms, e.g., for experiments with optical lattices. This mechanism may be cascaded to cover even larger distances for applications with quantum degenerate samples.Comment: 7 pages, 8 figure