Ed with receptor destroying enzyme (RDE) to inactivate non-specific inhibitors prior to HAI assay. A standard HAI assay [15] using chicken get AN 3199 erythrocytes with seasonal influenza strains or horse erythrocytes with HPAI strains was used to screen 22948146 for previous exposure in pre-study uninfected animals.Influenza Disease Profile in FerretsHemagglutination Inhibition Assay (HAI) and Median Tissue Culture Infectious Dose (TCID50)A standard HAI assay using chicken erythrocytes with seasonal influenza strains or horse erythrocytes with HPAI strains was used to screen for previous exposure in pre-study uninfected animals [15]. A standard TCID50 assay using MDCK cells was used to determine virus titer of tissue samples [16]. The presence of viral infection was determined by an in situ influenza A antinucleoprotein ELISA [15] and the titer was determined by the Spearman-Karber method [17]. ?intervals. These plots also indicate which comparisons were significantly different. Kaplan-Meier estimates were plotted and a log-rank test was performed to compare survival rates among the influenza virusinfected ferrets. The SASH MULTTEST procedure was used to adjust for multiple comparisons at the 0.05 level of significance using the Bonferroni-Holm method. Logistic regression models were fit to the change from 4EGI-1 baseline parameters to determine which variables were significantly associated with survival. These models included HPAI infected ferrets only because mortality was not observed in either of the other strains.Statistical AnalysesAnalysis of variance models were fitted to the data from each parameter at each time point. Hematology, clinical chemistry, CRP, and TCID50 data were log-transformed for analysis. These models were also fitted to the change from baseline data for each parameter except CRP, and TCID50. Baseline was defined as the last measured value before infection. The models were used to test for significant difference between each pair of parameters in the data or change from baseline data using a Bonferroni adjustment for the number of comparisons. Plots were produced showing means (weight, temperature, and activity) or geometric means (hematology, clinical chemistry, TCID50) and 95 confidenceAcknowledgmentsThe authors would like to thank the NIAID Program Managers, Ms. Susan Houser and Ms. Anika Chandler for their support of the NIAID program.Author ContributionsConceived and designed the experiments: EMV GVS. Performed the experiments: EMV GVS 
JPL MG BAC JF JEB. Analyzed the data: GVS EMV JPL SMM DIO. Contributed reagents/materials/analysis tools: GVS BAC JF. Wrote the paper: GVS EMV DIO.
Hereditary spastic paraplegia (HSP) constitutes a large, genetically diverse group of inherited neurologic disorders characterized by progressive spasticity and weakness of the lower limbs [1]. HSP is uncommon, but not rare, with a prevalence of ,3?/100,000 in most populations [1,2]. Inheritance may be X-linked recessive, autosomal recessive or dominant, and age at onset varies widely, from early childhood to adulthood [1,3]. HSP has historically been classified as `pure’ or `complicated’ on the basis of the absence (pure) or presence (complicated) of associated clinical features, such as distal amyotrophy, cognitive dysfunction, retinopathy, cataracts, ataxia, thin corpus callosum, peripheral neuropathy and deafness [1,2]. However, HSP is increasingly being classifiedgenetically, as genetic mapping has identified at least 52 different HSP loci, designated.Ed with receptor destroying enzyme (RDE) to inactivate non-specific inhibitors prior to HAI assay. A standard HAI assay [15] using chicken erythrocytes with seasonal influenza strains or horse erythrocytes with HPAI strains was used to screen 22948146 for previous exposure in pre-study uninfected animals.Influenza Disease Profile in FerretsHemagglutination Inhibition Assay (HAI) and Median Tissue Culture Infectious Dose (TCID50)A standard HAI assay using chicken erythrocytes with seasonal influenza strains or horse erythrocytes with HPAI strains was used to screen for previous exposure in pre-study uninfected animals [15]. A standard TCID50 assay using MDCK cells was used to determine virus titer of tissue samples [16]. The presence of viral infection was determined by an in situ influenza A antinucleoprotein ELISA [15] and the titer was determined by the Spearman-Karber method [17]. ?intervals. These plots also indicate which comparisons were significantly different. Kaplan-Meier estimates were plotted and a log-rank test was performed to compare survival rates among the influenza virusinfected ferrets. The SASH MULTTEST 
procedure was used to adjust for multiple comparisons at the 0.05 level of significance using the Bonferroni-Holm method. Logistic regression models were fit to the change from baseline parameters to determine which variables were significantly associated with survival. These models included HPAI infected ferrets only because mortality was not observed in either of the other strains.Statistical AnalysesAnalysis of variance models were fitted to the data from each parameter at each time point. Hematology, clinical chemistry, CRP, and TCID50 data were log-transformed for analysis. These models were also fitted to the change from baseline data for each parameter except CRP, and TCID50. Baseline was defined as the last measured value before infection. The models were used to test for significant difference between each pair of parameters in the data or change from baseline data using a Bonferroni adjustment for the number of comparisons. Plots were produced showing means (weight, temperature, and activity) or geometric means (hematology, clinical chemistry, TCID50) and 95 confidenceAcknowledgmentsThe authors would like to thank the NIAID Program Managers, Ms. Susan Houser and Ms. Anika Chandler for their support of the NIAID program.Author ContributionsConceived and designed the experiments: EMV GVS. Performed the experiments: EMV GVS JPL MG BAC JF JEB. Analyzed the data: GVS EMV JPL SMM DIO. Contributed reagents/materials/analysis tools: GVS BAC JF. Wrote the paper: GVS EMV DIO.
Hereditary spastic paraplegia (HSP) constitutes a large, genetically diverse group of inherited neurologic disorders characterized by progressive spasticity and weakness of the lower limbs [1]. HSP is uncommon, but not rare, with a prevalence of ,3?/100,000 in most populations [1,2]. Inheritance may be X-linked recessive, autosomal recessive or dominant, and age at onset varies widely, from early childhood to adulthood [1,3]. HSP has historically been classified as `pure’ or `complicated’ on the basis of the absence (pure) or presence (complicated) of associated clinical features, such as distal amyotrophy, cognitive dysfunction, retinopathy, cataracts, ataxia, thin corpus callosum, peripheral neuropathy and deafness [1,2]. However, HSP is increasingly being classifiedgenetically, as genetic mapping has identified at least 52 different HSP loci, designated.
