Entry and competition in generic biologics

Patents for several blockbuster biological products are expected to expire soon. The Food and Drug Administration is examining whether biologies can and should be treated like pharmaceuticals with regard to generics. In contrast with pharmaceuticals, which are manufactured through chemical synthesis, biologies are manufactured through fermentation, a process that is more variable and costly. Regulators might require extensive clinical testing of generic biologies to demonstrate equivalence to the branded product. The focus of the debate on generic biologies has been on legal and health concerns, but there are important economic implications. We combine a theoretical model of generic biologies with regression estimates from generic pharmaceuticals to estimate market entry and prices in the generic biologic market. We find that generic biologies will have high fixed costs from clinical testing and from manufacturing, so there will be less entry than would be expected for generic pharmaceuticals. With fewer generic competitors, generic biologies will be relatively close in price to branded biologies. Policy makers should be prudent in estimating financial benefits of generic biologies for consumers and payers. We also examine possible government strategies to promote generic competition. Copyright © 2007 John Wiley & Sons, Ltd.

Evolving brand-name and generic drug competition may warrant a revision of the Hatch-Waxman Act.

The evolution of pharmaceutical competition since Congress passed the Hatch-Waxman Act in 1984 raises questions about whether the act's intended balance of incentives for cost savings and continued innovation has been achieved. Generic drug usage and challenges to brand-name drugs' patents have increased markedly, resulting in greatly increased cost savings but also potentially reduced incentives for innovators. Congress should review whether Hatch-Waxman is achieving its intended purpose of balancing incentives for generics and innovation. It also should consider whether the law should be amended so that some of its provisions are brought more in line with recently enacted legislation governing approval of so-called biosimilars, or the corollary for biologics of generic competition for small-molecule drugs.

Decision making across social contexts: Competition increases preferences for risk in chimpanzees and bonobos

Context can have a powerful influence on decision-making strategies in humans. In particular, people sometimes shift their economic preferences depending on the broader social context, such as the presence of potential competitors or mating partners. Despite the important role of competition in primate conspecific interactions, as well as evidence that competitive social contexts impact primates' social cognitive skills, there has been little study of how social context influences the strategies that nonhumans show when making decisions about the value of resources. Here we investigate the impact of social context on preferences for risk (variability in payoffs) in our two closest phylogenetic relatives, chimpanzees, Pan troglodytes, and bonobos, Pan paniscus. In a first study, we examine the impact of competition on patterns of risky choice. In a second study, we examine whether a positive play context affects risky choices. We find that (1) apes are more likely to choose the risky option when making decisions in a competitive context; and (2) the play context did not influence their risk preferences. Overall these results suggest that some types of social contexts can shift patterns of decision making in nonhuman apes, much like in humans. Comparative studies of chimpanzees and bonobos can therefore help illuminate the evolutionary processes shaping human economic behaviour. © 2012 The Association for the Study of Animal Behaviour.

The Effects of Geography, Environment and Phylogeny on Community Assembly and Gene Flow Dynamics

It is increasingly evident that evolutionary processes play a role in how ecological communities are assembled. However the extend to which evolution influences how plants respond to spatial and environmental gradients and interact with each other is less clear. In this dissertation I leverage evolutionary tools and thinking to understand how space and environment affect community composition and patterns of gene flow in a unique system of Atlantic rainforest and restinga (sandy coastal plains) habitats in Southeastern Brazil.

In chapter one I investigate how space and environment affect the population genetic structure and gene flow of Aechmea nudicaulis, a bromeliad species that co-occurs in forest and restinga habitats. I genotyped seven microsatellite loci and sequenced one chloroplast DNA region for individuals collected in 7 pairs of forest / restinga sites. Bayesian genetic clustering analyses show that populations of A. nudicaulis are geographically structured in northern and southern populations, a pattern consistent with broader scale phylogeographic dynamics of the Atlantic rainforest. On the other hand, explicit migration models based on the coalescent estimate that inter-habitat gene flow is less common than gene flow between populations in the same habitat type, despite their geographic discontinuity. I conclude that there is evidence for repeated colonization of the restingas from forest populations even though the steep environmental gradient between habitats is a stronger barrier to gene flow than geographic distance.

In chapter two I use data on 2800 individual plants finely mapped in a restinga plot and on first-year survival of 500 seedlings to understand the roles of phylogeny, functional traits and abiotic conditions in the spatial structuring of that community. I demonstrate that phylogeny is a poor predictor of functional traits in and that convergence in these traits is pervasive. In general, the community is not phylogenetically structured, with at best 14% of the plots deviating significantly from the null model. The functional traits SLA, leaf dry matter content (LDMC), and maximum height also showed no clear pattern of spatial structuring. On the other hand, leaf area is strongly overdispersed across all spatial scales. Although leaf area overdispersion would be generally taken as evidence of competition, I argue that interpretation is probably misleading. Finally, I show that seedling survival is dramatically increased when they grow shaded by an adult individual, suggesting that seedlings are being facilitated. Phylogenetic distance to their adult neighbor has no influence on rates of survival though. Taken together, these results indicate that phylogeny has very limited influence on the fine scale assembly of restinga communities.

SELECTED REPERTOIRE OF THE GILLET COMPETITION FROM 1996 TO 2006

There are many bassoon competitions around the world- and one of the most famous is the Gillet competition, sponsored by the International Double Reed Society. In 1981, it was established as an annual event, the "Femand Gillet Bassoon Competition"- a title expanded in 2000 to the "Femand Gillet-Hugo Fox Bassoon Competition." My goal was to explore the history of the competition, the availability of the repertoire selected for each competition, and the difficulties performing each piece. Through this journey, I was able to discover the variety of material chosen and how it was used, the quality, value, and the importance of the repertoire in each competition. For example, Ferdinand David's Concertino op.12, the style of the piece provides romantic, operatic type lyricism, a flashy presto section and finale, makes it as a standard romantic piece in the bassoon repertoire; Otmar Nussio's Variations on an Air by Pergolesi, contains a slow theme and few diverse variations, which provides a contemporary style music with the traditional music form and descriptive quality. The result of learning this repertoire proves that different styles of music in the competition demonstrate the artistry of the bassoon repertoire and music history in relationship of the development of the instrument. My first dissertation recital featured: Concerto for Bassoon, K. 191 by Wolfgang Amadeus Mozart; Concertino by Marcel Bitsch; Metamorphoses by Leslie Bassett; and Sonatine by Alexandre Tansman. My second recital featured: Concerto in E minor, RV 484 by Antonio Vivaldi; On the Summer Map of Stars by Gordon Kerry; Concertino Opus12 by Ferdinand David; Elegie by Jacques Hetu; and Interferences by Roger Boutry. My third recital featured: Cello Suite No.2 in D minor, BWV1008 by Johann Sebastian Bach; Combinaciones: Sonatina para Fagot y Piano by Salvador Ranieri; Andante e Rondo Ungarese Opus 35 by Carl Maria von Weber; and Variations on an Air by Pergolesi for Bassoon and Piano by Otmar Nussio.

Inhibition-Induced Forgetting Results from Resource Competition between Response Inhibition and Memory Encoding Processes.

UNLABELLED: Response inhibition is a key component of executive control, but its relation to other cognitive processes is not well understood. We recently documented the "inhibition-induced forgetting effect": no-go cues are remembered more poorly than go cues. We attributed this effect to central-resource competition, whereby response inhibition saps attention away from memory encoding. However, this proposal is difficult to test with behavioral means alone. We therefore used fMRI in humans to test two neural predictions of the "common resource hypothesis": (1) brain regions associated with response inhibition should exhibit greater resource demands during encoding of subsequently forgotten than remembered no-go cues; and (2) this higher inhibitory resource demand should lead to memory encoding regions having less resources available during encoding of subsequently forgotten no-go cues. Participants categorized face stimuli by gender in a go/no-go task and, following a delay, performed a surprise recognition memory test for those faces. Replicating previous findings, memory was worse for no-go than for go stimuli. Crucially, forgetting of no-go cues was predicted by high inhibitory resource demand, as quantified by the trial-by-trial ratio of activity in neural "no-go" versus "go" networks. Moreover, this index of inhibitory demand exhibited an inverse trial-by-trial relationship with activity in brain regions responsible for the encoding of no-go cues into memory, notably the ventrolateral prefrontal cortex. This seesaw pattern between the neural resource demand of response inhibition and activity related to memory encoding directly supports the hypothesis that response inhibition temporarily saps attentional resources away from stimulus processing. SIGNIFICANCE STATEMENT: Recent behavioral experiments showed that inhibiting a motor response to a stimulus (a "no-go cue") impairs subsequent memory for that cue. Here, we used fMRI to test whether this "inhibition-induced forgetting effect" is caused by competition for neural resources between the processes of response inhibition and memory encoding. We found that trial-by-trial variations in neural inhibitory resource demand predicted subsequent forgetting of no-go cues and that higher inhibitory demand was furthermore associated with lower concurrent activation in brain regions responsible for successful memory encoding of no-go cues. Thus, motor inhibition and stimulus encoding appear to compete with each other: when more resources have to be devoted to inhibiting action, less are available for encoding sensory stimuli.

Inter-annual variability of precipitation constrains the production response of boreal Pinus sylvestris to nitrogen fertilization

© 2015 Published by Elsevier B.V.Tree growth resources and the efficiency of resource-use for biomass production determine the productivity of forest ecosystems. In nutrient-limited forests, nitrogen (N)-fertilization increases foliage [N], which may increase photosynthetic rates, leaf area index (L), and thus light interception (IC). The product of such changes is a higher gross primary production and higher net primary production (NPP). However, fertilization may also alter carbohydrate partitioning from below- to aboveground, increasing aboveground NPP (ANPP). We analyzed effects of long-term N-fertilization on NPP, and that of long-term carbon storing organs (NPPS) in a Pinus sylvestris forest on sandy soil, a wide-ranging forest type in the boreal region. We based our analyses on a combination of destructive harvesting, consecutive mensuration, and optical measurements of canopy openness. After eight-year fertilization with a total of 70gNm^-2, ANPP was 27±7% higher in the fertilized (F) relative to the reference (R) stand, but although L increased relative to its pre-fertilization values, IC was not greater than in R. On the seventh year after the treatment initiation, the increase of ANPP was matched by the decrease of belowground NPP (78 vs. 92gCm^-2yr^-1; ~17% of NPP) and, given the similarity of IC, suggests that the main effect of N-fertilization was changed carbon partitioning rather than increased canopy photosynthesis. Annual NPPS increased linearly with growing season temperature (T) in both treatments, with an upward shift of 70.2gCm^-2yr^-1 by fertilization, which also caused greater amount of unexplained variation (r²=0.53 in R, 0.21 in F). Residuals of the NPPS-T relationship of F were related to growing season precipitation (P, r²=0.48), indicating that T constrains productivity at this site regardless of fertility, while P is important in determining productivity where N-limitation is alleviated. We estimated that, in a growing season average T (11.5±1.0°C; 33-year-mean), NPPS response to N-fertilization will be nullified with P 31mm less than the mean (325±85mm), and would double with P 109mm greater than the mean. These results suggest that inter-annual variation in climate, particularly in P, may help explaining the reported large variability in growth responses to fertilization of pine stands on sandy soils. Furthermore, forest management of long-rotation systems, such as those of boreal and northern temperate forests, must consider the efficiency of fertilization in terms of wood production in the context of changes in climate predicted for the region.

Acquired epidermodysplasia verruciformis syndrome in HIV-infected pediatric patients: Prospective treatment trial with topical glycolic acid and human papillomavirus genotype characterization

SCOPUS: ar.j

What a performance! Developing nurse teachers lecturing persona and identity: a performing arts perspective

Delivering lectures to large groups of students can provoke high levels of anxiety, particularly for new lecturers (Exley and Dennick, 2009). Further, to provide an informative and engaging lecture requires a teacher who is confident, has a sound knowledge and well developed teaching skills (Bentley-Davies, 2010). Thus, new lecturers often need experience and supervision to develop the tacit knowledge and insight into their own style and persona when teaching in order to feel confident when delivering a lecture (Quinn and Hughes, 2007). Considering this model, therefore, may potentially contribute to a lecturers’ development and performance in the classroom. This paper will present the results of the second phase of a two-stage mixed method study that investigated the similarities between lecturing and acting. Twelve in-depth interviews where undertaken with lecturers within one School of Nursing in The United Kingdom. Findings, established a model of ‘persona adoption’ that represents a series of stages that lecturers may go through to both develop and take on a persona when lecturing. This persona is often different from the way they lecturers present themselves in other parts of their working life. The first stage of this model of persona adoption is when the lecturer is subjected to a range of ‘influencing factors’ that provide not only the basic information about a lecture, but also the perceptual stimuli about giving a lecture on a specific subject, to a particular number of students, at a certain academic level. These influencing factors then inter-play with the ‘facets of the individual’, which represent the lecturer’s self-concept, subject knowledge base and philosophy of teaching. This may result in a cognitive dissonance between these ‘facets’ and the ‘influencing factors’, so affecting the lecturers’ perceptions, thoughts and feelings about having to give that particular lecture. This results in the lecturer undertaking specific ‘back stage preparation’ during which they decide on the content and modes of delivery to prepare in light of that discourse. It may result in delivering the information via single or multiple methods, which during the lecture will require various levels of interaction and participation from the students. Just prior to the lecture, the lecturer builds or ‘puts on their persona’ and gets into role, making their initial impact with the group. They use the ‘elements of acting’ as proposed by Tauber and Mester’s (1994) e.g. animated voice and body, space, props humour and suspense and surprise to portray and maintain their persona. This leads the to lecturer demonstrating either positive or negative ‘persona characteristics’ in terms of appearing confident, knowledgeable, fluent in the technical skills of delivering the lecture, being interesting and engendering interaction with the students, or not. These characteristics, may or may not, potentially heighten student interest, attention and attitudes to learning as suggested by Tauber and Mester (1994). This depends on whether the lecturer has successfully used the persona and if the lecturer has been able to engage students in the lecture, in competition with other factors that may be taking the students’ attention. Although the model suggests a linear process, to a great extent, the elements might be more interdependent and interrelated. This might suggest that depending on the lecturer’s perception of their effectiveness during the lecture, that they may decide to continue or adapt their persona and methods to appear more confident. Furthermore, depending on how successful the lecturer perceived the session to be, both their reflections ‘in’ and ‘on’ practice could influence how they teach in the future (Zwozdiak, 2011). Therefore, these reflections become part of the facets of the individual, via the ‘reflective feedback loop’, in the model, which then in turn influences progression through the model in subsequent lectures. This study concluded that these lecturers went through a process whereby they compare the demands of the lecture with their own knowledge base and skill, this resulted in them undertaking specific preparation in terms of content and delivery style, then they adopted their persona immediately prior to entering the lecture, maintain it throughout the lecture via the use of the elements of acting to achieve an informative interactive lecture. The results of which then feedback into their self-concept as a lecturer and consequently may affect the persona they project in future lectures. If lecturers, therefore, can take a step back to consider how they deliver lectures and the way they can deliberately, yet apparently naturally, use their voices, bodies, space and humour in meaningfully, they engage their students in lecture, it will not just result in them being perceived as a good lecturer, but also be a genuine act of education.

Relational dimensions of corporate governance in translation: networked governance in China and India

The effectiveness of corporate governance mechanisms has been a subject of academic research for many decades. Although the large majority of corporate governance studies prior to mid 1990s were based on data from developed market economies such as the U.S., U.K. and Japan, in recent years researchers have begun examining corporate governance in transition economies. A comparison of China and India offers a unique environment for analyzing the effectiveness of corporate governance. First, both countries state-owned enterprise (SOE) reform strategies hinges on the Modern Enterprise System characterized by the separation of ownership and control. Ownership of an SOE’s assets is distributed among the government, institutional investors, managers, employees, and private investors. Effective control rights are assigned to management, which generally has a very small, or even nonexistent ownership stake. This distinctive shareholding structure creates conflict of interest not only between management (insiders) and outside investors but also between large shareholders and minority investors. Moreover, because both governments desire to retain some control—in part through partial retained ownership of commercialized SOEs, further conflicts arise between politicians and firms. Second, directors in publicly listed firms in both countries are predominantly drawn from institutions with significant non-market objectives: the government and other state enterprises, particularly in China, and extended families, particularly in India. As a result, the effectiveness of internal governance mechanisms, such as the number of independent directors on the board and the number of independent supervisors on the supervisory committee, are likely to be quiet limited, although this has yet to be fully evaluated. Third, because of the political nature of the privatization process itself, typical external governance mechanisms, such as debt (in conjunction with appropriate bankruptcy procedures), takeover threats, legal protection of investors, product market competition, etc., have not been effective. Bank loans have traditionally been viewed as grants from the state designed to bail out failing firms. State-owned banks retain monopoly or quasi-monopoly positions in the banking sector and profit is not their overriding objective. If political favor is deemed appropriate, subsidized loans, rescheduling of overdue debt or even outright transfer of funds can be arranged with SOEs (soft budget constraints). In addition, a market for private, non-bank debt is limited in India and has yet to be established China. There is no active merger or takeover activity in Chinese stock markets to discipline management. Information available in the capital markets is insufficient to keep at arm’s length of the corporate decisions. In light of the above peculiarities, China and India share many of the typical institutional characteristics as a transition economy, including poor legal protection of creditors and investors, the absence of an effective takeover market, an underdeveloped capital market, a relative inefficient banking system and significant interference of politicians in firm management. Su (2005) finds that the extent of political interference, managerial entrenchment and institutional control can help explain corporate dividend policies and post-IPO financing choices in this situation. Allen et al. (2005) demonstrate that standard corporate governance mechanisms are weak and ineffective for publicly listed firms while alternative governance mechanisms based on reputation and relationship have been remarkably effective in the private sector. Because the peculiarities are significant in this context, the differences in the political-economies of the two countries are likely to be evident in such relational terms. In this paper we explore the peculiarities of corporate governance in this transitional environment through a systematic examination of certain aspects of these reputational and relationship dimensions. Utilising the methods of social network analysis we identify the inter-organisational relationships at board level formed by equity holdings and by shared directors. Using data drawn from the Orbis database we map these relations among the 3700 largest firms in India and China respectively and identify the roles played in these relational networks by the particularly characteristic institutions in each case. We find greatly different social network structures in each case with some support in these relational dimensions for their distinctive features of governance. Further, the social network metrics allow us to considerably refine proxies for political interference, managerial entrenchment and institutional control used in earlier econometric analysis.

The illusions of competition in the water sector: a response to the OFWAT/Cave consultations on introducing competition in the water sector in England and Wales

The paper provides a critical review of the role of liberalisation and competition in the water sector, based on empirical evidence from the UK and internationally. The paper is submitted as evidence to the official reviews of competition in water sector in England and Wales.

Visualization of polyphonic voices inter-animation in CSCL chats

Trausan-Matu, S., & Dascalu, M. (2015). Visualization of Polyphonic Voices Inter-animation in CSCL Chats. Revista Romana de Interactiune Om-Calculator, 8(4), 305–322.