A Difference in Heterosubtypic Immunity Induced by a Modified Live Attenuated Avian Influenza Backbone in Mice and Ferrets

The unprecedented emergence of multiple avian influenza virus (AIV) subtypes with a broad host range poses a major challenge in the design of vaccination strategies that are effective against multiple subtypes of influenza. The present study focused on the protective effects of a modified AIV as a backbone for epidemic and pandemic influenza. In addition, the ability of this backbone to induce heterosubtypic immunity (Het-I) was also analyzed. Het-I is the ability of one influenza subtype to protect against a different influenza subtype. Previously, a live attenuated AIV with the internal backbone of A/guinea fowl/Hong Kong/WF10/99 (H9N2) (WF10), called WF10att, protected chickens against a lethal influenza challenge. To characterize the WF10att backbone as a master donor strain and determine its ability to induce Het-I, we evaluated its protective efficacy in mice and ferrets. Vaccinated mice were protected against homologous challenge with A/WSN/1933 (H1N1) (WSN), mouse-adapted A/California/04/2009 (pH1N1) and A/Vietnam/1203/2004 (H5N1) (HPAI H5N1) viruses, and ferrets survived homologous challenge with HPAI H5N1. H7N2att vaccinated mice were protected against both H1N1 and HPAI H5N1 challenge; however, Het-I was observed in H9N2att vaccinated ferrets challenged with HPAI H5N1. We found that both B and T cells are involved in the Het-I induced by our WF10att backbone. Cross-reactive non-neutralizing antibodies to viral proteins were detected. JhD-/- mice, which lack mature B-lymphocytes, were vaccinated with the recombinant vaccines and challenged with HPAI H5N1. None of the vaccinated mice survived challenge further suggesting a role for Het-I. In addition, cells isolated from the lungs of H7N2att vaccinated mice had cross-reactive antibody-secreting cells targeted to HPAI H5N1. Together, these results suggest a role for B cells in Het-I. Although B cells are important, T cells may also play a role in Het-I. Both IFN-γ and Granzyme B secreting cells were detected in lung and spleen cells isolated from H7N2att vaccinated mice and stimulated with HPAI H5N1 suggesting a role for T cells in Het-I. The ability of our WF10att backbone to induce Het-I depends on the surface glycoproteins expressed and the challenge virus subtype. In addition, WF10att uses both B and T cells to induce Het-I

Folgers: The New Era of Coffee

The primary purpose of this paper is to discuss the repositioning of the Folgers brand through a new and improved Brand Pyramid and two strategic recommendations. In order to come to these conclusions, the group utilized secondary research to gain a background on the coffee industry as a whole, the acquisition of the Folgers brand by Smucker’s, the competition relative to Folgers in the coffee market, a social media analysis focusing on the competitors, and finally research regarding the Millennial generation. The conclusions from this secondary research led to the methodology used in order to come up with the new pyramid and recommendations. This methodology included two surveys, the first being sent out to friends and relatives through the use of social media, and the second which utilized the tool Survey Monkey Audience, which was sent to a paid panel of 18-34 year-old coffee drinkers. A stipend of $500 was utilized by the group in order to use the survey resources and to provide monetary rewards to participants in said surveys

Deletions in the neuraminidase stalk region of H2N2 and H9N2 avian influenza virus subtypes do not affect postinfluenza secondary bacterial pneumonia

We investigated the synergism between influenza virus and Streptococcus pneumoniae, particularly the role of deletions in the stalk region of the neuraminidase (NA) of H2N2 and H9N2 avian influenza viruses. Deletions in the NA stalk (ΔNA) had no effect on NA activity or on the adherence of S. pneumoniae to virus-infected human alveolar epithelial (A549) and mouse lung adenoma (LA-4) cells, although it delayed virus elution from turkey red blood cells. Sequential S. pneumoniae infection of mice previously inoculated with isogenic recombinant H2N2 and H9N2 influenza viruses displayed severe pneumonia, elevated levels of intrapulmonary proinflammatory responses, and death. No differences between the WT and ΔNA mutant viruses were detected with respect to effects on postinfluenza pneumococcal pneumonia as measured by bacterial growth, lung inflammation, morbidity, mortality, and cytokine/chemokine concentrations. Differences were observed, however, in influenza virus-infected mice that were treated with oseltamivir prior to a challenge with S. pneumoniae. Under these circumstances, mice infected with ΔNA viruses were associated with a better prognosis following a secondary bacterial challenge. These data suggest that the H2N2 and H9N2 subtypes of avian influenza A viruses can contribute to secondary bacterial pneumonia and deletions in the NA stalk may modulate its outcome in the context of antiviral therapy. © 2012, American Society for Microbiology.Fil: Chockalingam, Ashok K.. University of Maryland; Estados UnidosFil: Hickman, Danielle. University of Maryland; Estados UnidosFil: Pena, Lindomar. University of Maryland; Estados UnidosFil: Ye, Jianqiang. University of Maryland; Estados UnidosFil: Ferrero, Andrea. University of Maryland; Estados UnidosFil: Echenique, Jose Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Chen, Hongjun. University of Maryland; Estados UnidosFil: Sutton, Troy. University of Maryland; Estados UnidosFil: Perez, Daniel R.. University of Maryland; Estados Unido

Planning for the future- Response from the UWE Bristol Planning School and Centre for Sustainable Planning and Environments

A response to the consultation attached to Planning For the Future (https://www.gov.uk/government/consultations/planning-for-the-future

‘Back to Life’—Using knowledge exchange processes to enhance lifestyle interventions for liver transplant recipients: A qualitative study

Interventions to prevent excessive weight gain after liver transplant are needed. The purpose of the present study was to enhance a specialist post-transplant well-being program through knowledge exchange with end-users.The study used an interactive process of knowledge exchange between researchers, clinicians and health system users. Data were collected as focus groups or telephone interviews and underwent applied thematic analysis.There were 28 participants (age 24-68 years; 64% male). The results identified experiences that may influence decisions around health behaviours during the course of transplant recovery. Three over-arching themes were identified that impact on liver transplant recipients post-transplant health behaviours. These include (i) Finding a coping mechanism which highlighted the need to acknowledge the significant emotional burden of transplant prior to addressing long-term physical wellness; (ii) Back to Life encompassing the desire to return to employment and prioritise family, while co-ordinating the burden of ongoing medical monitoring and self-management and (iii) Tailored, Personalised Care with a preference for health care delivery by transplant specialists via a range of flexible eHealth modalities.This person-centred process of knowledge exchange incorporated experiences of recipients into service design and identified life priorities most likely to influence health behaviours post-transplant. Patient co-creation of services has the potential to improve the integration of knowledge into health systems and future directions will require evaluation of effectiveness and sustainability of patient-centred multidisciplinary service development

Housing affordability in the South West of England

The South West faces acute problems of housing affordability. The region is conspicuously less affordable than England as a whole, and the North and Midlands in particular. These inter-regional disparities are becoming progressively more pronounced.• The South West is the fourth least affordable region in England for all property types (after London, South East and the East of England). In 2021, median house prices were approximately ten times greater than the median earnings.• The South West is becoming less affordable over time. In 1997, median house prices were approximately four times greater than the median earnings. Affordability ratios in the South West (plus London, South East and the East of England) continue to be above the English median, and the gap is widening.• Three quarters (22 out of 29) of local authority areas in the South West have affordability ratios higher than that for England as a whole, and all have affordability ratios higher than those for the North East, North West, and Yorkshire and the Humber.• There is substantial diversity in affordability ratios between local authority areas in the South West, varying from 7.3 in Plymouth (a ratio that is still higher than those for North East, North West, and Yorkshire and the Humber) to 15.8 in Cotswolds District.• There is also substantial diversity in affordability ratios within local authority areas in the South West. The ten least affordable neighbourhoods in the South West have median house prices more than 28.3 times median earnings, these are in the Bath and NorthEast Somerset, Cotswolds, Cornwall, Bournemouth, Christchurch and Poole. Even in the most affordable neighbourhoods of Plymouth and Gloucester median house prices are still more than three times median earnings.• This is the first time that a granular assessment of affordability has been provided for the region, and it demonstrates the variation within local authorities. This is likely to be particularly important in larger, rural authorities where it might be more challenging to commute to home and other services

Expression of Porcine Fusion Protein IRF7/3(5D) Efficiently Controls Foot-and-Mouth Disease Virus Replication

Several studies have demonstrated that the delivery of type I, II, or III interferons (IFNs) by inoculation of a replication-defective human adenovirus 5 (Ad5) vector expressing IFNs can effectively control foot-and-mouth disease (FMD) in cattle and swine during experimental infections. However, relatively high doses are required to achieve protection. In this study, we identified the functional properties of a porcine fusion protein, poIRF7/3(5D), as a biotherapeutic and enhancer of IFN activity against FMD virus (FMDV). We showed that poIRF7/3(5D) is a potent inducer of type I IFNs, including alpha IFN (IFN-α), IFN-β, and IFN-ω but not type III IFN (interleukin-28B), without inducing cytotoxicity. Expression of poIRF7/3(5D) significantly and steadily reduced FMDV titers by up to 6 log(10) units in swine and bovine cell lines. Treatment with an IFN receptor inhibitor (B18R) combined with an anti-IFN-α antibody neutralized the antiviral activity in the supernatants of cells transduced with an Ad5 vector expressing poIRF7/3(5D) [Ad5-poIRF7/3(5D)]. However, several transcripts with known antiviral function, including type I IFNs, were still highly upregulated (range of increase, 8-fold to over 500-fold) by poIRF7/3(5D) in the presence of B18R. Furthermore, the sera of mice treated with Ad5-poIRF7/3(5D) showed antiviral activity that was associated with the induction of high levels of IFN-α and resulted in complete protection against FMDV challenge at 6, 24, or 48 h posttreatment. This study highlights for the first time the antiviral potential of Ad5-poIRF7/3(5D) in vitro and in vivo against FMDV. IMPORTANCE FMD remains one of the most devastating diseases that affect livestock worldwide. Effective vaccine formulations are available but are serotype specific and require approximately 7 days before they are able to elicit protective immunity. We have shown that vector-delivered IFN is an option to protect animals against many FMDV serotypes as soon as 24 h and for about 4 days postadministration. Here we demonstrate that delivery of a constitutively active transcription factor that induces the production of endogenous IFNs and potentially other antiviral genes is a viable strategy to protect against FMD