Evidence of 'evergreening' in secondary patenting of blockbuster drugs

Secondary patents associated with blockbuster drugs are granted for follow-on innovations relating to the active pharmaceutical ingredient (‘API’) of the drug. Our analysis of all sec-ondary patents for 13 top-selling drugs in Australia shows that, while the majority of fol-low-on innovations are made by entities other than the originator of the drug, the innova-tions with the highest private value are undertaken by the drug’s originator and concern a delivery mechanism or an alternative formulation for the API. Since that is the type of follow-on innovation most commonly undertaken by drug originators, and considered most likely to result in a de facto extension of marketplace monopoly over the drug, we see in these findings evidence that the originators of blockbuster drugs engage in secondary patenting that has an ‘evergreening’ effect

Can the United States Afford a “No-Fault” System of Compensation for Medical Injury?

One of the key issues separating US critics of a no-fault alternative to the tort system for compensating victims of medical injury from supporters is its anticipated cost. Results from a study are presented that estimate the costs of a no-fault system, one that is similar to the system now in operation in Sweden, within the context of the US health care system

Overview of Mollisols in the world: Distribution, land use and management

Mollisols a.k.a., Black Soils or Prairie Soils make up about 916 million ha, which is 7% of the world’s ice-free land surface. Their distribution strongly correlates with native prairie ecosystems, but is not limited to them. They are most prevalent in the mid-latitudes of North America, Eurasia, and South America. In North America, they cover 200 million ha of the United States, more than 40 million ha of Canada and 50 million ha of Mexico. Across Eurasia they cover around 450 million ha, extending from the western 148 million ha in southern Russia and 34 million ha in Ukraine to the eastern 35 million ha in northeast China. They are common to South America’s Argentina and Uruguay, covering about 89 million and 13 million ha, respectively. Mollisols are often recognized as inherently productive and fertile soils. They are extensively and intensively farmed, and increasingly dedicated to cereals production, which needs significant inputs of fertilizers and tillage. Mollisols are also important soils in pasture, range and forage systems. Thus, it is not surprising that these soils are prone to soil erosion, dehumification (loss of stable aggregates and organic matter) and are suffering from anthropogenic soil acidity. Therefore, soil scientists from all of the world’s Mollisols regions are concerned about the sustainability of some of current trends in land use and agricultural practices. These same scientists recommend increasing the acreage under minimum or restricted tillage, returning plant residues and adding organic amendments such as animal manure to maintain or increase soil organic matter content, and more systematic use of chemical amendments such as agricultural limestone to replenish soil calcium reserves

Universal architecture of bacterial chemoreceptor arrays

Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and precise adaptation of the signaling system. Previous structural and genomic studies have produced conflicting models, however, for the arrangement of the chemoreceptors in the clusters. Using whole-cell electron cryo-tomography, here we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed “trimer of dimers” organization. The various observed lengths of the receptors confirm current models for the methylation, flexible bundle, signaling, and linker sub-domains in vivo. Our results suggest that the basic mechanism and function of receptor clustering is universal among bacterial species and was thus conserved during evolution

Soil quality assessment based on soil organic matter pools under long‐term tillage systems and following tillage conversion in a semi‐humid region

A field study was conducted to assess the long-term effects of no-tillage (NT) and conventional tillage (CT), and the short-term effects following tillage conversion -from CT to NT (NTn) and from NT to CT (CTn) on soil quality (SQ) indicators in a semi-humid climate. First, plots of a long-term tillage experiment on a Luvic Phaeozem initiated in 1986, were split into two subplots in 2012, yielding four treatments: NT, CT, NTn and CTn. In 2015, composite soil samples were collected from each treatment and from a natural site (Ref) at depths 0-5, 5-10, 10-20 and 0-20 cm. Several indicators were determined: soil organic carbon (SOC) and nitrogen (SON); particulate organic C (POM-C) and N (POM-N); potential N mineralization (PMN) and soil respiration (Rs). Moreover, bulk density was determined in long-term tillage systems. Different ratios between indicators were calculated, with emphasis on its function in the agroecosystem, i.e. functional indicators. Significant differences in SOC, SON and PMN were found between CT and NT at most depths. In contrast, three years after tillage conversion, only a part of the SQ indicators studied were modified mainly at the 0-10 cm depth. The functional indicators showed differences between tillage systems in the long-term and after short-term tillage conversion depending on the depth; however, the PMN/SON ratio demonstrated differences at all depths. Under these conditions, this ratio -related to easily mineralizable N fraction- proved to be a promising indicator for assessing SQ under contrasting tillage systems regardless of the sampling depth.Fil: Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; ArgentinaFil: Galantini, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Duval, Matias Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: López, Fernando Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentin

Applied Theatre and Practice as Research: Polyphonic Conversations

Applied theatre practice as research might be perceived as a curious conflation. Not greatly foregrounded in the literature on applied theatre or performance practice as research, this article engages with the particularities of such a pairing. Beginning with identifying why a consideration is timely, ‘the practice as research’ and ‘social’ turns are invoked and analysed as relevant contexts to consider applied theatre practice as research. Two projects are offered, providing specific examples for discussion. Revealed by increased scrutiny, some broader epistemological questions emerge concerning power, hierarchy of knowledge and research ‘authoring’. A metaphor of polyphonic conversations is offered as an amplification of the applied theatre practical research methodological terrain. Encouraging the basis of many sets of voices contributing to research and potentially negotiating concerns about power hierarchies and knowledge production, the metaphor provokes a fluidity of epistemology, including expanding on the now familiar debates around theory and practice particularly relevant for socially engaged performance-related practical research

Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed

The motor theory of speech perception holds that we perceive the speech of another in terms of a motor representation of that speech. However, when we have learned to recognize a foreign accent, it seems plausible that recognition of a word rarely involves reconstruction of the speech gestures of the speaker rather than the listener. To better assess the motor theory and this observation, we proceed in three stages. Part 1 places the motor theory of speech perception in a larger framework based on our earlier models of the adaptive formation of mirror neurons for grasping, and for viewing extensions of that mirror system as part of a larger system for neuro-linguistic processing, augmented by the present consideration of recognizing speech in a novel accent. Part 2 then offers a novel computational model of how a listener comes to understand the speech of someone speaking the listener's native language with a foreign accent. The core tenet of the model is that the listener uses hypotheses about the word the speaker is currently uttering to update probabilities linking the sound produced by the speaker to phonemes in the native language repertoire of the listener. This, on average, improves the recognition of later words. This model is neutral regarding the nature of the representations it uses (motor vs. auditory). It serve as a reference point for the discussion in Part 3, which proposes a dual-stream neuro-linguistic architecture to revisits claims for and against the motor theory of speech perception and the relevance of mirror neurons, and extracts some implications for the reframing of the motor theory

Integration of Consonant and Pitch Processing as Revealed by the Absence of Additivity in Mismatch Negativity

Consonants, unlike vowels, are thought to be speech specific and therefore no interactions would be expected between consonants and pitch, a basic element for musical tones. The present study used an electrophysiological approach to investigate whether, contrary to this view, there is integrative processing of consonants and pitch by measuring additivity of changes in the mismatch negativity (MMN) of evoked potentials. The MMN is elicited by discriminable variations occurring in a sequence of repetitive, homogeneous sounds. In the experiment, event-related potentials (ERPs) were recorded while participants heard frequently sung consonant-vowel syllables and rare stimuli deviating in either consonant identity only, pitch only, or in both dimensions. Every type of deviation elicited a reliable MMN. As expected, the two single-deviant MMNs had similar amplitudes, but that of the double-deviant MMN was also not significantly different from them. This absence of additivity in the double-deviant MMN suggests that consonant and pitch variations are processed, at least at a pre-attentive level, in an integrated rather than independent way. Domain-specificity of consonants may depend on higher-level processes in the hierarchy of speech perception