Franchising: A New Twist With Old Roots

In the relatively short time since its post-World War II emergence, franchising has become a significant factor in the global economy, representing one of the fastest growing methods of both expanding a business (as a franchiser) and starting a business (as a franchisee). U.S. franchise revenues account for more than 40% of all retail sales and total more than a trillion dollars in revenues annually (International Franchise Association, 2004a). Within the franchise industry, the fast food segment contributes a significant portion of revenues, over $120 billion, with the trend expected to increase due to global expansion (Nation’s Restaurant News, 2006). Despite the relatively new approach to business that franchising offers, a number of the concepts upon which franchising are built can be found in a historical review of management principles. From Fayol to Taylor and Follet, the applicability of their theories continues to stand the test of time, including the franchise industry. The purpose of this paper is thus to address some of the historical management principles that are found in and applied to the area of fast food franchising

THE RELATIONSHIP BETWEEN HIGH-PERFORMANCE HUMAN RESOURCE MANAGEMENT, ORGANIZATIONAL CITIZENSHIP BEHAVIOR, AND UNIT PERFORMANCE AND VOLUNTARY TURNOVER IN THE FAST FOOD FRANCHISE INDUSTRY

The purpose of this study is to advance knowledge and practitioner understanding of human resource dynamics of the U.S. fast food franchise (FFF) industry, one plagued by extraordinary voluntary turnover (VTO), estimated at 75% of total turnover, and its effects on unit productivity. Following the research of Sun, Aryee, and Law (2007), this study looks for the potential of improving the VTO problem through the practice of high-performance human resource management (HPHRM) and the potential benefits of service-oriented organizational citizenship behavior (SOCB) that it offers. This study used primary research, namely the domestic operating units of a nationally franchised sub sandwich chain, with a sample size of 112 units representing 14.8% of the total units and the evaluation of 336 hourly employees. Results showed a strong correlation between HPHRM and VTO, but surprisingly there was no significant relationship between HPHRM and productivity. Despite a modest correlation between HPHRM and SOCB, that relationship did not demonstrate any significant mediating effect on the HPHRM/VTO relationship. The results may indicate a differentiation between the effectiveness of HPHRM and SOCB depending on the performance level of hourly employees, noting that low-performing employees do not respond to HPHRM or demonstrate SOCB as well as others. Numerous opportunities for further research are suggested, especially in light of the size and impact of the domestic FFF industry

Replication of Synthetic Defective Interfering RNAs Derived from Coronavirus Mouse Hepatitis Virus-A59

AbstractWe have analyzed the replication of deletion mutants of defective interfering (DI) RNAs derived from the coronavirus mouse hepatitis virus (MHV)-A59 in the presence of MHV-A59. Using two parental DI RNAs, MIDI and MIDIΔH, a twin set of deletion mutants was generated with progressively shorter stretches of 5′ sequence colinear with the genomic RNA. All deletion mutants contained in-frame ORFs. We show that in transfected cells and after one passage the DI RNAs were detectable and that their accumulation was positively correlated with the length of 5′ sequence they contained. However, accumulation of two twin mutants, Δ2, in which sequences from nucleotide position 467 were fused to those from position 801, was undetectable. In passage 4 cells, but not in transfected or in passage 1 cells, recombination with genomic RNA led to the appearance of the parental DI RNAs. The accumulation of these parental RNAs was inversely correlated with the length of 5′ sequence on the deletion mutants and was highest in the Δ2 samples. In sharp contrast to the data reported for MHV-JHM-derived DI RNAs, we show that MHV-A59-derived mutant RNAs do not require an internal sequence domain for replication. The data suggest that coronavirus replication involves an RNA superstructure at the 5′ end of the genome or one comprising both ends of the genomic RNA. We also conclude from the recombination data that in-frame mutants with impaired replication signals are more fit than out-frame mutants with intact replication signals

Are we prepared for emerging flaviviruses in Europe? Challenges for vaccination.

Tick-borne encephalitis and West Nile fever are endemic flavivirus diseases in Europe. Climate change, virus evolution, and social factors may increase the risk of these flavivirus infections and may lead to the emergence of other flaviviruses in Europe that are endemic in (sub)tropical regions of the world. Control of the spread of flaviviruses is very difficult considering the cycling of flaviviruses between arthropod vectors and animal reservoir hosts. The increasing threat of flavivirus infections emphasizes the necessity of a sustainable vector surveillance system, an active animal health surveillance system and an adequate human surveillance system for early detection of flavivirus infections. Vaccination is the most important approach to prevent flavivirus infections. Effective inactivated whole virus vaccines against tick-borne encephalitis (TBE) infection are available. Implementation of TBE vaccination based on favorable cost-effectiveness estimates per region and per target group can reduce the disease burden of TBE infection. At present, several West Nile virus (WNV) vaccine candidates are in various stages of clinical development. A major challenge for WNV vaccine candidates is to demonstrate efficacy, because of the sporadic nature of unpredictable WNV outbreaks. Universal WNV vaccination is unlikely to be cost-effective, vaccination of high-risk groups will be most appropriate to protect against WNV infections

An international technology platform for influenza vaccines

AbstractSince 2008, the World Health Organization has provided seed grants to 11 manufacturers in low- and middle-income countries to establish or improve their pandemic influenza vaccine production capacity. To facilitate this ambitious project, an influenza vaccine technology platform (or “hub”) was established at the Netherlands Vaccine Institute for training and technology transfer to developing countries. During its first two years of operation, a robust and transferable monovalent pilot process for egg-based inactivated whole virus influenza A vaccine production was established under international Good Manufacturing Practice standards, as well as in-process and release assays. A course curriculum was designed, including a two-volume practical handbook on production and quality control. Four generic hands-on training courses were successfully realized for over 40 employees from 15 developing country manufacturers. Planned extensions to the curriculum include cell-culture based technology for viral vaccine production, split virion influenza production, and generic adjuvant formulation. We conclude that technology transfer through the hub model works well, significantly builds vaccine manufacturing capacity in developing countries, and thereby increases global and equitable access to vaccines of high public health relevance

Contributing factors to influenza vaccine uptake in general hospitals:an explorative management questionnaire study from the Netherlands

BACKGROUND: The influenza vaccination rate in hospitals among health care workers in Europe remains low. As there is a lack of research about management factors we assessed factors reported by administrators of general hospitals that are associated with the influenza vaccine uptake among health care workers. METHODS: All 81 general hospitals in the Netherlands were approached to participate in a self-administered questionnaire study. The questionnaire was directed at the hospital administrators. The following factors were addressed: beliefs about the effectiveness of the influenza vaccine, whether the hospital had a written policy on influenza vaccination and how the hospital informed their staff about influenza vaccination. The questionnaire also included questions about mandatory vaccination, whether it was free of charge and how delivered as well as the vaccination campaign costs. The outcome of this one-season survey is the self-reported overall influenza vaccination rate of health care workers. RESULTS: In all, 79 of 81 hospitals that were approached were willing to participate and therefore received a questionnaire. Of these, 42 were returned (response rate 52%). Overall influenza vaccination rate among health care workers in our sample was 17.7% (95% confidence interval: 14.6% to 20.8%). Hospitals in which the administrators agreed with positive statements concerning the influenza vaccination had a slightly higher, but non-significant, vaccine uptake. There was a 9% higher vaccine uptake in hospitals that spent more than €1250,- on the vaccination campaign (24.0% versus 15.0%; 95% confidence interval from 0.7% to 17.3%). CONCLUSIONS: Agreement with positive statements about management factors with regard to influenza vaccination were not associated with the uptake. More economic investments were related with a higher vaccine uptake; the reasons for this should be explored further

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

H7N9 influenza split vaccine with SWE oil-in-water adjuvant greatly enhances cross-reactive humoral immunity and protection against severe pneumonia in ferrets

Until universal influenza vaccines become available, pandemic preparedness should include developing classical vaccines against potential pandemic influenza subtypes. We here show that addition of SWE adjuvant, a squalene-in-water emulsion, to H7N9 split influenza vaccine clearly enhanced functional antibody responses in ferrets. These were cross-reactive against H7N9 strains from different lineages and newly emerged H7N9 variants. Both vaccine formulations protected in almost all cases against severe pneumonia induced by intratracheal infection of ferrets with H7N9 influenza; however, the SWE adjuvant enhanced protection against virus replication and disease. Correlation analysis and curve fitting showed that both VN- and NI-titers were better predictors for protection than HI-titers. Moreover, we show that novel algorithms can assist in better interpretation of large data sets generated in preclinical studies. Cluster analysis showed that the adjuvanted vaccine results in robust immunity and protection, whereas the response to the non-adjuvanted vaccine is heterogeneous, such that the protection balance may be more easily tipped toward severe disease. Finally, cluster analysis indicated that the dose-sparing capacity of the adjuvant is at least a factor six, which greatly increases vaccine availability in a pandemic situation.</p

Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections and hospitalization in infants under 1 year of age and there is currently no market-approved vaccine available. For protection against infection, young children mainly depend on their innate immune system and maternal antibodies. Traditionally, antibody-mediated protection against viral infections is thought to be mediated by direct binding of antibodies to viral particles, resulting in virus neutralization. However, in the case of RSV, virus neutralization titers do not provide an adequate correlate of protection. The current lack of understanding of the mechanisms by which antibodies can protect against RSV infection and disease or, alternatively, contribute to disease severity, hampers the design of safe and effective vaccines against this virus. Importantly, neutralization is only one of many mechanisms by which antibodies can interfere with viral infection. Antibodies consist of two structural regions: a variable fragment (Fab) that mediates antigen binding and a constant fragment (Fc) that mediates downstream effector functions via its interaction with Fc-receptors on (innate) immune cells or with C1q, the recognition molecule of the complement system. The interaction with Fc-receptors can lead to killing of virus-infected cells through a variety of immune effector mechanisms, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Antibody-mediated complement activation may lead to complement-dependent cytotoxicity (CDC). In addition, both Fc-receptor interactions and complement activation can exert a broad range of immunomodulatory functions. Recent studies have emphasized the importance of Fc-mediated antibody effector functions in both protection and pathogenesis for various infectious agents. In this review article, we aim to provide a comprehensive overview of the current knowledge on Fc-mediated antibody effector functions in the context of RSV infection, discuss their potential role in establishing the balance between protection and pathogenesis, and point out important gaps in our understanding of these processes. Furthermore, we elaborate on the regulation of these effector functions on both the cellular and humoral side. Finally, we discuss the implications of Fc-mediated antibody effector functions for the rational design of safe and effective vaccines and monoclonal antibody therapies against RSV

In Vitro Enhancement of Respiratory Syncytial Virus Infection by Maternal Antibodies Does Not Explain Disease Severity in Infants.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mainly below 6 months of age, when neutralizing matAb levels are present. To investigate this discrepancy, we asked if disease severity is related to antibody properties other than neutralization. Some antibody effector functions are mediated via their Fc binding region. However, it has been shown that this binding may lead to antibody-dependent enhancement (ADE) of infection or reduction of neutralization, both possibly leading to more disease. In this study, we first showed that high levels of ADE of RSV infection occur in monocytic THP-1 cells in the presence of RSV antibodies and that neutralization by these antibodies was reduced in Vero cells when they were transduced with Fc gamma receptors. We then demonstrated that antibodies from cotton rats with formalin-inactivated (FI)-RSV-induced pulmonary pathology were capable of causing ADE. Human matAbs also caused ADE and were less neutralizing in vitro in cells that carry Fc receptors. However, these effects were unrelated to disease severity because they were seen both in uninfected controls and in infants hospitalized with different levels of RSV disease severity. We conclude that ADE and reduction of neutralization are unlikely to be involved in RSV disease in infants with neutralizing matAbs.IMPORTANCE It is unclear why severity of RSV disease peaks at the age when infants have neutralizing levels of maternal antibodies. Additionally, the exact reason for FI-RSV-induced enhanced disease, as seen in the 1960s vaccine trials, is still unclear. We hypothesized that antibodies present under either of these conditions could contribute to disease severity. Antibodies can have effects that may lead to more disease instead of protection. We investigated two of those effects: antibody-dependent enhancement of infection (ADE) and neutralization reduction. We show that ADE occurs in vitro with antibodies from FI-RSV-immunized RSV-infected cotton rats. Moreover, passively acquired maternal antibodies from infants had the capacity to induce ADE and reduction of neutralization. However, no clear association with disease severity was seen, ruling out that these properties explain disease in the presence of maternal antibodies. Our data contribute to a better understanding of the impact of antibodies on RSV disease in infants