Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study.

BACKGROUND: The incidence and outcomes of respiratory viral infections in lung transplant recipients (LTR) are not well defined. The objective of this prospective study conducted from June 2008 to March 2011 was to characterise the incidence and outcomes of viral respiratory infections in LTR. METHODS: Patients were seen in three contexts: study-specific screenings covering all seasons; routine post-transplantation follow-up; and emergency visits. Nasopharyngeal specimens were collected systematically and bronchoalveolar lavage (BAL) was performed when clinically indicated. All specimens underwent testing with a wide panel of molecular assays targeting respiratory viruses. RESULTS: One hundred and twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were routine post-transplantation follow-up and 209 (23%) were emergency visits. Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral infection rates upon screening, routine and emergency visits were 14%, 15% and 34%, respectively (p<0.001). Picornavirus was identified most frequently in nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral carriage, mainly of picornaviruses, was found at 10% of screening visits. Infections were associated with transient lung function loss and high calcineurin inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%) for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI 0.1 to 1.3). CONCLUSIONS: There is a high incidence of viral infection in LTR; asymptomatic carriage is rare. Viral infections contribute significantly to this population's respiratory symptomatology. No temporal association was observed between infection and acute rejection.

Business Organization and Coordination in Marketing Specialty Hogs: A Comparative Analysis of Two Firms from Iowa, November 2005

We study business organization and coordination of specialty-market hog production using a comparative analysis of two Iowa pork niche-marketing firms. We describe and analyze each firms management of five key organizational challenges: planning and logistics, quality assurance, process verication and management of �credence attributes,� business structure, and profit sharing. Although each firm is engaged in essentially the same activity, there are substantial differences across the two firms in the way production and marketing are coordinated. These differences are partly explained by the relative size and age of each firm, thus highlighting the importance of organizational evolution in agricultural markets, but are also partly the result of a formal organizational separation between marketing and production activities in one of the firm.

Viral transport of DNA damage that mimics a stalled replication fork.

Adeno-associated virus type 2 (AAV2) infection incites cells to arrest with 4N DNA content or die if the p53 pathway is defective. This arrest depends on AAV2 DNA, which is single stranded with inverted terminal repeats that serve as primers during viral DNA replication. Here, we show that AAV2 DNA triggers damage signaling that resembles the response to an aberrant cellular DNA replication fork. UV treatment of AAV2 enhances the G2 arrest by generating intrastrand DNA cross-links which persist in infected cells, disrupting viral DNA replication and maintaining the viral DNA in the single-stranded form. In cells, such DNA accumulates into nuclear foci with a signaling apparatus that involves DNA polymerase delta, ATR, TopBP1, RPA, and the Rad9/Rad1/Hus1 complex but not ATM or NBS1. Focus formation and damage signaling strictly depend on ATR and Chk1 functions. Activation of the Chk1 effector kinase leads to the virus-induced G2 arrest. AAV2 provides a novel way to study the cellular response to abnormal DNA replication without damaging cellular DNA. By using the AAV2 system, we show that in human cells activation of phosphorylation of Chk1 depends on TopBP1 and that it is a prerequisite for the appearance of DNA damage foci.

The impact of fibrosis and steatosis on early viral kinetics in HCV genotype 1-infected patients treated with Peg-IFN-alfa-2a and ribavirin.

Summary.  Hepatitis C viral (HCV) kinetics after initiation of interferon-based therapy provide valuable insights for understanding virus pathogenesis, evaluating treatment antiviral effectiveness and predicting treatment outcome. Adverse effects of liver fibrosis and steatosis on sustained virological response have been frequently reported, yet their impacts on the early viral kinetics remain unclear. In this study, associations between histology status and early viral kinetics were assessed in 149 HCV genotype 1-infected patients treated with pegylated interferon alfa-2a and ribavirin (DITTO trial). In multivariate analyses adjusted for critical factors such as IL28B genotype and baseline viral load, presence of significant fibrosis (Ishak stage > 2) was found to independently reduce the odds of achieving an initial reduction (calculated from day 0 to day 4) in HCV RNA of ≥2 logIU/mL (adjusted OR 0.03, P = 0.004) but was not associated with the second-phase slope of viral decline (calculated from day 8 to day 29). On the contrary, presence of liver steatosis was an independent risk factor for not having a rapid second-phase slope, that is, ≥0.3 logIU/mL/week (adjusted OR 0.22, P = 0.012) but was not associated with the first-phase decline. Viral kinetic modelling theory suggests that significant fibrosis primarily impairs the treatment antiviral effectiveness in blocking viral production by infected cells, whereas the presence of steatosis is associated with a lower net loss of infected cells. Further studies will be necessary to identify the biological mechanisms underlain by these findings.

Early neutralizing antibody response against mouse mammary tumor virus: critical role of viral infection and superantigen-reactive T cells.

Infectious mouse mammary tumor virus (MMTV) is a retrovirus that expresses a superantigen shortly after infection of B cells. The superantigen first drives the polyclonal activation and proliferation of superantigen-reactive CD4+ T cells, which then induce the infected B cells to proliferate and differentiate. Part of the MMTV-induced B cell response leads to the production of Abs that are specific for the viral envelope protein gp52. Here we show that this Ab response has virus-neutralizing activity and confers protection against superinfection by other MMTV strains in vivo as soon as 4 to 7 days after infection. A protective Ab titer is maintained lifelong. Viral infection as well as the superantigen-induced T-B collaboration are required to generate this rapid and long lasting neutralizing Ab response. Polyclonal or superantigen-independent B cell activation, on the contrary, does not lead to detectable virus neutralization. The early onset of this superantigen-dependent neutralizing response suggests that viral envelope-specific B cells are selectively recruited to form part of the extrafollicular B cell response and are subsequently amplified and maintained by superantigen-reactive Th cells.

Estratègies de marketing per assolir l'èxit : llançament d'una revista per a joves

Actualment, en aquesta societat és difícil introduir un nou producte al mercat degut alshàbits de consum adquirits per la població. Per tal de superar aquests obstacles, el marketing actual s'ha tornat més complex i sofisticat. Per tot això, s’analitzaran els passos que s'han de seguir per tenir èxit a l'hora de llançar un nou producte.Per començar, s’enfocarà el tema en un únic producte, una revista dirigida a un públic entre 16 i 30 anys aproximadament. Així doncs, es suposarà una situació fictícia on una empresa independent, que està intentant introduir una nova publicació al mercat de la premsa escrita, contractarà un estudi de marketing per decidir els continguts de la revista, a quin tipus de consumidors estarà dirigida i analitzar els punts forts i febles de la competència per saber quina directriu hauria de seguir l’estratègia comercial.Seguidament, es decidirà la marca de la revista: el títol i el disseny del logotip. El preu òptim de llançament, els mitjans de comunicació que s’utilitzarien per donar a conèixer la revista, quins canals de distribució es seguirien i quins serien els punts de venda. Per tot això, es realitzaran enquestes i es faran diversos estudis sobre l’entorn general de l’empresa i la situació actual del sector.Amb tot això volem aconseguir el següent objectiu: ¿Quines estratègies de marketings'haurien de seguir per assolir l'èxit?

Estimating the basic reproductive number from viral sequence data.

Epidemiological processes leave a fingerprint in the pattern of genetic structure of virus populations. Here, we provide a new method to infer epidemiological parameters directly from viral sequence data. The method is based on phylogenetic analysis using a birth-death model (BDM) rather than the commonly used coalescent as the model for the epidemiological transmission of the pathogen. Using the BDM has the advantage that transmission and death rates are estimated independently and therefore enables for the first time the estimation of the basic reproductive number of the pathogen using only sequence data, without further assumptions like the average duration of infection. We apply the method to genetic data of the HIV-1 epidemic in Switzerland.

Collective Marketing Arrangements for Geographically Differentiated Agricultural Products: Welfare Impacts and Policy Implications, May 2006

This paper examines the incentive of atomistic agricultural producers within a specific geographical region to differentiate and collectively market products. We develop a model that allows us to analyze the market and welfare effects of the main types of real-world producer organizations, using it to derive economic insights regarding the circumstances under which these organizations will evolve, and describing implications of the results obtained in the context of an ongoing debate between the European Union and United States. As the anticipated fixed costs of development and marketing increase and the anticipated size of the market falls, it becomes essential to increase the ability of the producer organization to control supply in order to ensure the coverage of fixed costs. Whenever a collective organization allows a market (with a new product) to exist that otherwise would not have existed there is an increase in societal welfare. Counterintuitively, stronger property right protection for producer organizations may be welfare enhancing even after a differentiated product has been developed. The reason for this somewhat paradoxical result is that legislation aimed at curtailing the market power of producer organizations may induce large technological distortions.

Iowa Turkey Marketing Council, Independent Auditor's Reports, Financial Statement, Schedule of Findings, December 31, 2004 & 2005

State Audit Reports

Comunicação de Marketing na Formação da Imagem dos Destinos Turísticos: o caso de Cabo Verde

Segundo a Organização Mundial do Turismo (OMT), o turismo é a maior indústria do séc. XXI gerando anualmente milhares de milhões de dólares em divisas para a economia de inúmeros países. Por apresentar um conjunto de características muito específicas, o sucesso desta actividade é fortemente condicionado pela imagem que os turistas e potenciais turistas apresentam relativamente a um determinado destino. Apesar de existirem muitos factores que interferem na formação desta imagem, a comunicação de marketing é apontada, pelos investigadores, como um dos elementos que desempenha um papel crucial neste âmbito. O objecto do presente trabalho de investigação é a comunicação de marketing na formação da imagem dos destinos turísticos particularizando o arquipélago de Cabo Verde. O principal objectivo da pesquisa, é analisar a eficácia da comunicação de marketing de três organizações (Cabo Verde – Investimentos, União Nacional dos Operadores Turísticos e operador Soltropico), na promoção do arquipélago de Cabo Verde, enquanto destino turístico, no mercado português. Para a realização deste estudo empírico, foram definidas três hipóteses. Essas hipóteses foram testadas através do cruzamento da informação proveniente de uma entrevista realizada aos directores de marketing de cada uma das três organizações, com os dados obtidos a partir da análise de conteúdo dos instrumentos de comunicação que têm vindo a ser utilizados pelas respectivas entidades para promover o destino e com as respostas de um conjunto de 115 turistas portugueses, a um questionário cujo assunto se encontra relacionado com os principais atributos de Cabo Verde enquanto destino de férias. A investigação realizada permitiu verificar que, de uma forma geral, existe uma sintonia entre os atributos de Cabo Verde que as organizações têm intenção de divulgar, os atributos deste destino que são transmitidos pelos seus instrumentos comunicação e os principais atributos do arquipélago indicados pelos turistas portugueses. Contudo, os resultados do estudo revelam também a necessidade de se introduzir algumas correcções a nível de conteúdos e imagens que se encontram presentes nos instrumentos de comunicação de algumas das organizações, visando a criação de uma imagem mais atractiva deste destino.

Comunicação de Marketing na Formação da Imagem dos Destinos Turísticos: o caso de Cabo Verde

Segundo a Organização Mundial do Turismo (OMT), o turismo é a maior indústria do séc. XXI gerando anualmente milhares de milhões de dólares em divisas para a economia de inúmeros países. Por apresentar um conjunto de características muito específicas, o sucesso desta actividade é fortemente condicionado pela imagem que os turistas e potenciais turistas apresentam relativamente a um determinado destino. Apesar de existirem muitos factores que interferem na formação desta imagem, a comunicação de marketing é apontada, pelos investigadores, como um dos elementos que desempenha um papel crucial neste âmbito. O objecto do presente trabalho de investigação é a comunicação de marketing na formação da imagem dos destinos turísticos particularizando o arquipélago de Cabo Verde. O principal objectivo da pesquisa, é analisar a eficácia da comunicação de marketing de três organizações (Cabo Verde – Investimentos, União Nacional dos Operadores Turísticos e operador Soltropico), na promoção do arquipélago de Cabo Verde, enquanto destino turístico, no mercado português. Para a realização deste estudo empírico, foram definidas três hipóteses. Essas hipóteses foram testadas através do cruzamento da informação proveniente de uma entrevista realizada aos directores de marketing de cada uma das três organizações, com os dados obtidos a partir da análise de conteúdo dos instrumentos de comunicação que têm vindo a ser utilizados pelas respectivas entidades para promover o destino e com as respostas de um conjunto de 115 turistas portugueses, a um questionário cujo assunto se encontra relacionado com os principais atributos de Cabo Verde enquanto destino de férias. A investigação realizada permitiu verificar que, de uma forma geral, existe uma sintonia entre os atributos de Cabo Verde que as organizações têm intenção de divulgar, os atributos deste destino que são transmitidos pelos seus instrumentos comunicação e os principais atributos do arquipélago indicados pelos turistas portugueses. Contudo, os resultados do estudo revelam também a necessidade de se introduzir algumas correcções a nível de conteúdos e imagens que se encontram presentes nos instrumentos de comunicação de algumas das organizações, visando a criação de uma imagem mais atractiva deste destino.

Viral-mediated overexpression of mutant huntingtin to model HD in various species.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the huntingtin (Htt) gene. Despite intensive efforts devoted to investigating the mechanisms of its pathogenesis, effective treatments for this devastating disease remain unavailable. The lack of suitable models recapitulating the entire spectrum of the degenerative process has severely hindered the identification and validation of therapeutic strategies. The discovery that the degeneration in HD is caused by a mutation in a single gene has offered new opportunities to develop experimental models of HD, ranging from in vitro models to transgenic primates. However, recent advances in viral-vector technology provide promising alternatives based on the direct transfer of genes to selected sub-regions of the brain. Rodent studies have shown that overexpression of mutant human Htt in the striatum using adeno-associated virus or lentivirus vectors induces progressive neurodegeneration, which resembles that seen in HD. This article highlights progress made in modeling HD using viral vector gene transfer. We describe data obtained with of this highly flexible approach for the targeted overexpression of a disease-causing gene. The ability to deliver mutant Htt to specific tissues has opened pathological processes to experimental analysis and allowed targeted therapeutic development in rodent and primate pre-clinical models.

Audit report on the Iowa Turkey Marketing Council for the years ended December 31, 2006 and 2005

Audit report on the Iowa Turkey Marketing Council for the years ended December 31, 2006 and 2005

Viral superantigen drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.

Mouse mammary tumor virus (MMTV[SW]) encodes a superantigen expressed by infected B cells. It evokes an antibody response specific for viral envelope protein, indicating selective activation of antigen-specific B cells. The response to MMTV(SW) in draining lymph nodes was compared with the response to haptenated chicken gamma globulin (NP-CGG) using flow cytometry and immunohistology. T cell priming occurs in both responses, with T cells proliferating in association with interdigitating dendritic cells in the T zone. T cell proliferation continues in the presence of B cells in the outer T zone, and B blasts then undergo exponential growth and differentiation into plasma cells in the medullary cords. Germinal centers develop in both responses, but those induced by MMTV(SW) appear later and are smaller. Most T cells activated in the T zone and germinal centers in the MMTV(SW) response are superantigen specific and these persist for weeks in lymph nodes draining the site MMTV(SW) injection: this contrasts with the selective loss of superantigen-specific T cells from other secondary lymphoid tissues. The results indicate that this viral superantigen, when expressed by professional antigen-presenting cells, drives extrafollicular and follicular B cell differentiation leading to virus-specific antibody production.