The simple economics of risk-sharing agreements between the NHS and the pharmaceutical industry

The Janssen-Cilag proposal for a risk-sharing agreement regarding bortezomib received a welcome signal from NICE. The Office of Fair Trading report included risk-sharing agreements as an available tool for the National Health Service. Nonetheless, recent discussions have somewhat neglected the economic fundamentals underlying risk-sharing agreements. We argue here that risk-sharing agreements, although attractive due to the principle of paying by results, also entail risks. Too many patients may be put under treatment even with a low success probability. Prices are likely to be adjusted upward, in anticipation of future risk-sharing agreements between the pharmaceutical company and the third-party payer. An available instrument is a verification cost per patient treated, which allows obtaining the first-best allocation of patients to the new treatment, under the risk sharing agreement. Overall, the welfare effects of risk-sharing agreements are ambiguous, and care must be taken with their use.

Learning management systems in higher education

The use of Laptops and the Internet has produced the technological conditions for instructors and students can take advantage from the diversity of online information, communication, collaboration and sharing with others. The integration of Internet services in the teaching practices can be responsible for thematic, social and digital improvement for the agents involved. There are many benefits when we use a Learning Management Systems (LMS) such as Moodle, to support the lectures in higher education. We also will consider its implications for student support and online interaction, leading educational agents to a collaborating of different learning environments, where they can combine face-to-face instruction with computer-mediated instruction, blended-learning, and increases the possibilities for better quality and quantity of human communication in a learning background. In general components of learning management systems contain synchronous and asynchronous communication tools, management features, and assessment utilities. These assessment utilities allow lecturers to systematize basic assessment tasks. Assessments can be straightaway delivered to the student, and upon conclusion, immediately returned with grades and detailed feedback. Therefore learning management systems can also be used for assessment purposes in Higher Education.

Real-time scheduling with resource sharing on heterogeneous multiprocessors

Consider the problem of scheduling a task set τ of implicit-deadline sporadic tasks to meet all deadlines on a t-type heterogeneous multiprocessor platform where tasks may access multiple shared resources. The multiprocessor platform has m k processors of type-k, where k∈{1,2,…,t}. The execution time of a task depends on the type of processor on which it executes. The set of shared resources is denoted by R. For each task τ i , there is a resource set R i ⊆R such that for each job of τ i , during one phase of its execution, the job requests to hold the resource set R i exclusively with the interpretation that (i) the job makes a single request to hold all the resources in the resource set R i and (ii) at all times, when a job of τ i holds R i , no other job holds any resource in R i . Each job of task τ i may request the resource set R i at most once during its execution. A job is allowed to migrate when it requests a resource set and when it releases the resource set but a job is not allowed to migrate at other times. Our goal is to design a scheduling algorithm for this problem and prove its performance. We propose an algorithm, LP-EE-vpr, which offers the guarantee that if an implicit-deadline sporadic task set is schedulable on a t-type heterogeneous multiprocessor platform by an optimal scheduling algorithm that allows a job to migrate only when it requests or releases a resource set, then our algorithm also meets the deadlines with the same restriction on job migration, if given processors 4×(1+MAXP×⌈|P|×MAXPmin{m1,m2,…,mt}⌉) times as fast. (Here MAXP and |P| are computed based on the resource sets that tasks request.) For the special case that each task requests at most one resource, the bound of LP-EE-vpr collapses to 4×(1+⌈|R|min{m1,m2,…,mt}⌉). To the best of our knowledge, LP-EE-vpr is the first algorithm with proven performance guarantee for real-time scheduling of sporadic tasks with resource sharing on t-type heterogeneous multiprocessors.

New Features to Look at Natural Phenomena

Proceeding of the 3rd International Conference on Fractional Systems and Signals, at Ghent, Belgium

Specific features of endothelial cells in primary tumors

RESUMO: As células endoteliais definem e delineiam todo o sistema vascular...Nesta tese procurámos explorar o papel que o ambiente tumoral exerce sobre as células endoteliais. ... Avaliamos também a capacidade anti-angiogénica de alguns derivados do estrogénio... Em suma os nossos resultados mostram a importância de um controlo rigoroso da regulação transcricional...

Bits, Atoms, and Information Sharing: new opportunities for participation

The particular characteristics and affordances of technologies play a significant role in human experience by defining the realm of possibilities available to individuals and societies. Some technological configurations, such as the Internet, facilitate peer-to-peer communication and participatory behaviors. Others, like television broadcasting, tend to encourage centralization of creative processes and unidirectional communication. In other instances still, the affordances of technologies can be further constrained by social practices. That is the case, for example, of radio which, although technically allowing peer-to-peer communication, has effectively been converted into a broadcast medium through the legislation of the airwaves. How technologies acquire particular properties, meanings and uses, and who is involved in those decisions are the broader questions explored here. Although a long line of thought maintains that technologies evolve according to the logic of scientific rationality, recent studies demonstrated that technologies are, in fact, primarily shaped by social forces in specific historical contexts. In this view, adopted here, there is no one best way to design a technological artifact or system; the selection between alternative designs—which determine the affordances of each technology—is made by social actors according to their particular values, assumptions and goals. Thus, the arrangement of technical elements in any technological artifact is configured to conform to the views and interests of those involved in its development. Understanding how technologies assume particular shapes, who is involved in these decisions and how, in turn, they propitiate particular behaviors and modes of organization but not others, requires understanding the contexts in which they are developed. It is argued here that, throughout the last century, two distinct approaches to the development and dissemination of technologies have coexisted. In each of these models, based on fundamentally different ethoi, technologies are developed through different processes and by different participants—and therefore tend to assume different shapes and offer different possibilities. In the first of these approaches, the dominant model in Western societies, technologies are typically developed by firms, manufactured in large factories, and subsequently disseminated to the rest of the population for consumption. In this centralized model, the role of users is limited to selecting from the alternatives presented by professional producers. Thus, according to this approach, the technologies that are now so deeply woven into human experience, are primarily shaped by a relatively small number of producers. In recent years, however, a group of three interconnected interest groups—the makers, hackerspaces, and open source hardware communities—have increasingly challenged this dominant model by enacting an alternative approach in which technologies are both individually transformed and collectively shaped. Through a in-depth analysis of these phenomena, their practices and ethos, it is argued here that the distributed approach practiced by these communities offers a practical path towards a democratization of the technosphere by: 1) demystifying technologies, 2) providing the public with the tools and knowledge necessary to understand and shape technologies, and 3) encouraging citizen participation in the development of technologies.

CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features.

Peripheral T-cell lymphoma, not otherwise specified is a heterogeneous group of aggressive neoplasms with indistinct borders. By gene expression profiling we previously reported unsupervised clusters of peripheral T-cell lymphomas, not otherwise specified correlating with CD30 expression. In this work we extended the analysis of peripheral T-cell lymphoma molecular profiles to prototypical CD30(+) peripheral T-cell lymphomas (anaplastic large cell lymphomas), and validated mRNA expression profiles at the protein level. Existing transcriptomic datasets from peripheral T-cell lymphomas, not otherwise specified and anaplastic large cell lymphomas were reanalyzed. Twenty-one markers were selected for immunohistochemical validation on 80 peripheral T-cell lymphoma samples (not otherwise specified, CD30(+) and CD30(-); anaplastic large cell lymphomas, ALK(+) and ALK(-)), and differences between subgroups were assessed. Clinical follow-up was recorded. Compared to CD30(-) tumors, CD30(+) peripheral T-cell lymphomas, not otherwise specified were significantly enriched in ALK(-) anaplastic large cell lymphoma-related genes. By immunohistochemistry, CD30(+) peripheral T-cell lymphomas, not otherwise specified differed significantly from CD30(-) samples [down-regulated expression of T-cell receptor-associated proximal tyrosine kinases (Lck, Fyn, Itk) and of proteins involved in T-cell differentiation/activation (CD69, ICOS, CD52, NFATc2); upregulation of JunB and MUM1], while overlapping with anaplastic large cell lymphomas. CD30(-) peripheral T-cell lymphomas, not otherwise specified tended to have an inferior clinical outcome compared to the CD30(+) subgroups. In conclusion, we show molecular and phenotypic features common to CD30(+) peripheral T-cell lymphomas, and significant differences between CD30(-) and CD30(+) peripheral T-cell lymphomas, not otherwise specified, suggesting that CD30 expression might delineate two biologically distinct subgroups.

Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.

The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.

Sharing data between LSDBs and central repositories.

Several Locus-Specific DataBases (LSDBs) have recently been approached by larger, more general data repositories (including NCBI and UCSC) with the request to share the DNA variant data they have collected. Within the Human Genome Variation Society (HGVS) a document was generated summarizing the issues related to these requests. The document has been circulated in the HGVS/LSDB community and was discussed extensively. Here we summarize these discussions and present the concluded recommendations for LSDB data sharing with central repositories.

Association of PCK1 with Body Mass Index and Other Metabolic Features in Patients With Psychotropic Treatments.

Weight gain is a major health problem among psychiatric populations. It implicates several receptors and hormones involved in energy balance and metabolism. Phosphoenolpyruvate carboxykinase 1 is a rate-controlling enzyme involved in gluconeogenesis, glyceroneogenesis and cataplerosis and has been related to obesity and diabetes phenotypes in animals and humans. The aim of this study was to investigate the association of phosphoenolpyruvate carboxykinase 1 polymorphisms with metabolic traits in psychiatric patients treated with psychotropic drugs inducing weight gain and in general population samples. One polymorphism (rs11552145G > A) significantly associated with body mass index in the psychiatric discovery sample (n = 478) was replicated in 2 other psychiatric samples (n1 = 168, n2 = 188), with AA-genotype carriers having lower body mass index as compared to G-allele carriers. Stronger associations were found among women younger than 45 years carrying AA-genotype as compared to G-allele carriers (-2.25 kg/m, n = 151, P = 0.009) and in the discovery sample (-2.20 kg/m, n = 423, P = 0.0004). In the discovery sample for which metabolic parameters were available, AA-genotype showed lower waist circumference (-6.86 cm, P = 0.008) and triglycerides levels (-5.58 mg/100 mL, P < 0.002) when compared to G-allele carriers. Finally, waist-to-hip ratio was associated with rs6070157 (proxy of rs11552145, r = 0.99) in a population-based sample (N = 123,865, P = 0.022). Our results suggest an association of rs11552145G > A polymorphism with metabolic-related traits, especially in psychiatric populations and in women younger than 45 years.

Knowledge sharing in virtual communities

The Internet has transformed the scope, boundaries and dynamics of social and economic interactions. It is argued to have broadened the notion of the community from physical, colocated groups towards collectives that are able to transcend time and space, i.e. virtual communities. Even if virtual communities have been on the academic agenda for a couple of decades, there is still surprisingly little research on knowledge sharing within them. In addition, prior research has largely neglected the complex dynamics between Internet-based communication channels and the surrounding communities in which they are embedded. This thesis aims at building a better understanding of knowledge sharing supported by conversational technologies in intra-organisational virtual communities and external virtual communities supporting relationships with customers. The focus is thus on knowledge sharing in types of virtual communities that seem to be of relevance to business organisations. The study consists of two parts. The first part introduces the research topic and discusses the overall results. The second part comprises seven research publications. Qualitative research methods are used throughout the study. The results of the study indicate that investigation of the processes of knowledge sharing in virtual communities requires a socio-technical perspective, combining the individual, social and technological levels, and understanding the interplay between them. It is claimed that collective knowledge in virtual communities creates the enabling structure for knowledge sharing, and forms the invisible structure of the community on the basis of which it operates. It consists of a shared context, social capital and a unique community culture. The Internet does not inevitably erode social interaction: it seems that supporting social relationships by means of communication technology is a matter of quantity rather than quality. In order to provide access to external knowledge and expertise, firms need to open themselves up to an array of Internet-based conversations, and to consider the relevance of virtual communities to their businesses.

Individual difference factors and men's attraction to female body features /

Existing research on attraction to body features has suggested that men show general preferences for women with lower waist-to-hip ratios (WHR), larger breasts, and slender body weights. The present study intended to expand on this research by investigating several individual difference factors and their potential contribution to variation in what men find attractive in female body features. Two hundred and seventy-three men were assessed for sex-role identity, 2D:4D digit ratios (a possible marker of prenatal exposure to androgens, and thus masculinization), physical attractiveness, early sexual experiences (as indices of early sexual conditioning), and early family attitudes toward body features, as well as their current preferences for WHR, breast size, weight, and height in women. For WHR, as predicted, physical attractiveness, early sexual experiences, and lower (more masculine) right-hand 2D:4D ratios significantly predicted current preferences for more feminine (lower) WHR. Early sexual experiences significantly predicted later preferences for breast size; in addition, more masculine occupational preferences and lower (more masculine) left-hand 2D:4D ratios predicted preferences for larger breasts. Participants' height, education level, Unmitigated Agency (masculinity) scores, and early sexual experiences significantly predicted current preferences for height. Finally, early sexual experiences significantly predicted current preferences for weight. The results suggest that variation in preferences for women's bodily features can be uniquely accounted for by a number of individual difference factors. Strengths and weaknesses of the study, along with implications for future research, are discussed.

The principal in the high school: effectiveness in a climate of sharing

This pilot study developed a climate instrument which was administered in a sample of high schools in one board of education. Several tests were conducted i n order to determine the reliability and internal consistency of the instrument . The ability of the instrument to identify the demographic differences of school and gender was also tested. The relationship between leadership styles and an effective use of authority in creating a productive and rewarding work environment was the f ocus of t his study. Attitudes to leadership and perceived school morale were investigated in a demographic study, a climate survey, as well as a body of related literature. In light of the empirical research, an attempt was made to determine the extent to which the authority figure's behaviour and adopted leadership style contributed to a positive school climate : one in which t eachers were motivated to achieve to t he best of their abilities by way of their commitment and service. The tone of authority assumed by t he leader not only shapes the mood of the school environment but ultimately determines the efficiency and morale of t he teaching staff.

Is more information always good? : investigating the impact of website interface features on e-retailer's sales performance

A number of frameworks have been suggested for online retailing, but still there exists little consensus among researchers and practitioners regarding the appropriate amount of information critical and essential to the improvement of customers' satisfaction and their purchase intention. Against this backdrop, this study contributes to the current practical and theoretical discussions and conversations about how information search and perceived risk theories can be applied to the management of online retailer website features. This paper examines the moderating role of website personalization in studying the relationship between information content provided on the top US retailers' websites, and customer satisfaction and purchase intention. The study also explores the role played by customer satisfaction and purchase intention in studying the relationship between information that is personalized to the needs of individual customers and online retailers' sales performance. Results indicate that the extent of information content features presented to online customers alone is not enough for companies looking to satisfy and motivate customers to purchase. However, information that is targeted to an individual customer influences customer satisfaction and purchase intention, and customer satisfaction in tum serves as a driver to the retailer's online sales performance.