Better Mechanisms Are Needed to Oversee HREC Reviews

Better Mechanisms Are Needed to Oversee HREC Review

Boxplots of Average Number of Transplanted Organs per DBD and DCD Donor.

<p>Mean difference for number of transplants by donor type = 1.51 (95% CI: 1.42,1.60, p<0.001).</p

Listing of Countries Utilizing DCD and Relevant Maastricht Categories (Adapted from Dominguez-Gil B, Haase-Kromwijk B, Van Leiden H, Neuberger J, Coene L, et al.) [18].

<p>In addition to the countries listed above, the following countries have reported occasional, very low rates of DCD donation activity since 2000: Algeria, Bolivia, Brazil, Croatia, Hong Kong SARC, Lebanon, Pakistan, Romania, Saudi Arabia, Singapore, South Korea, Turkey and Ukraine.</p

Transplant Rate by (a) Donation after Brain Death (DBD) rate and (b) Donation after Cardiocirculatory Death (DCD) rate.

<p>Solid lines are the Lowess curve of the predicted values from the fitted model.</p

Average (a) Deceased Donors (DD), (b) Donation after Brain Death (DBD) and (c) Donation after Cardiocirculatory Death (DCD) rates over time by Group One (solid line), Group Two (dashed line) and Group Three (dotted line) countries.

<p>Average (a) Deceased Donors (DD), (b) Donation after Brain Death (DBD) and (c) Donation after Cardiocirculatory Death (DCD) rates over time by Group One (solid line), Group Two (dashed line) and Group Three (dotted line) countries.</p

Donation after Brain Death (DBD) rates vs (a) Donation after Cardiocirculatory Death (DCD) rate (b) controlled Donation after Cardiocirculatory Death (cDCD) rate and (c) uncontrolled Donation after Cardiocirculatory Death (uDCD) rate.

<p>Solid lines are the Lowess curve of the predicted values from the fitted model.</p

Image_5_H7N9 bearing a mutation in the nucleoprotein leads to increased pathology in chickens.jpeg

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI). Viral genome sequencing revealed two key mutations had occurred following infection in the haemagglutinin (HA 226 L>Q) and nucleoprotein (NP 373 A>T) proteins. We further investigated the impact of the NP mutation and demonstrated that only chickens bearing a single nucleotide polymorphism (SNP) in their IFITM1 gene were susceptible to the H7N9 virus. Susceptible chickens demonstrated a distinct loss of CD8+ T cells from the periphery as well as a dysregulation of IFNγ that was not observed for resistant chickens, suggesting a role for the NP mutation in altered T cell activation. Alternatively, it is possible that this mutation led to altered polymerase activity, as the mutation occurs in the NP 360-373 loop which has been previously show to be important in RNA binding. These data have broad ramifications for our understanding of the pathobiology of AI in chickens and humans and provide an excellent model for investigating the role of antiviral genes in a natural host species.</p

Image_3_H7N9 bearing a mutation in the nucleoprotein leads to increased pathology in chickens.jpeg

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI). Viral genome sequencing revealed two key mutations had occurred following infection in the haemagglutinin (HA 226 L>Q) and nucleoprotein (NP 373 A>T) proteins. We further investigated the impact of the NP mutation and demonstrated that only chickens bearing a single nucleotide polymorphism (SNP) in their IFITM1 gene were susceptible to the H7N9 virus. Susceptible chickens demonstrated a distinct loss of CD8+ T cells from the periphery as well as a dysregulation of IFNγ that was not observed for resistant chickens, suggesting a role for the NP mutation in altered T cell activation. Alternatively, it is possible that this mutation led to altered polymerase activity, as the mutation occurs in the NP 360-373 loop which has been previously show to be important in RNA binding. These data have broad ramifications for our understanding of the pathobiology of AI in chickens and humans and provide an excellent model for investigating the role of antiviral genes in a natural host species.</p

Image_2_H7N9 bearing a mutation in the nucleoprotein leads to increased pathology in chickens.jpeg

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI). Viral genome sequencing revealed two key mutations had occurred following infection in the haemagglutinin (HA 226 L>Q) and nucleoprotein (NP 373 A>T) proteins. We further investigated the impact of the NP mutation and demonstrated that only chickens bearing a single nucleotide polymorphism (SNP) in their IFITM1 gene were susceptible to the H7N9 virus. Susceptible chickens demonstrated a distinct loss of CD8+ T cells from the periphery as well as a dysregulation of IFNγ that was not observed for resistant chickens, suggesting a role for the NP mutation in altered T cell activation. Alternatively, it is possible that this mutation led to altered polymerase activity, as the mutation occurs in the NP 360-373 loop which has been previously show to be important in RNA binding. These data have broad ramifications for our understanding of the pathobiology of AI in chickens and humans and provide an excellent model for investigating the role of antiviral genes in a natural host species.</p

Image_1_H7N9 bearing a mutation in the nucleoprotein leads to increased pathology in chickens.jpeg

The zoonotic H7N9 avian influenza (AI) virus first emerged in 2013 as a low pathogenic (LPAI) strain, and has repeatedly caused human infection resulting in severe respiratory illness and a mortality of ~39% (>600 deaths) across five epidemic waves. This virus has circulated in poultry with little to no discernible clinical signs, making detection and control difficult. Contrary to published data, our group has observed a subset of specific pathogen free chickens infected with the H7N9 virus succumb to disease, showing clinical signs consistent with highly pathogenic AI (HPAI). Viral genome sequencing revealed two key mutations had occurred following infection in the haemagglutinin (HA 226 L>Q) and nucleoprotein (NP 373 A>T) proteins. We further investigated the impact of the NP mutation and demonstrated that only chickens bearing a single nucleotide polymorphism (SNP) in their IFITM1 gene were susceptible to the H7N9 virus. Susceptible chickens demonstrated a distinct loss of CD8+ T cells from the periphery as well as a dysregulation of IFNγ that was not observed for resistant chickens, suggesting a role for the NP mutation in altered T cell activation. Alternatively, it is possible that this mutation led to altered polymerase activity, as the mutation occurs in the NP 360-373 loop which has been previously show to be important in RNA binding. These data have broad ramifications for our understanding of the pathobiology of AI in chickens and humans and provide an excellent model for investigating the role of antiviral genes in a natural host species.</p