WHAT YOU SHOULD KNOW ABOUT HOG CHOLERA

I. WHAT IS HOG CHOLERA? Hog cholera is a deadly, contagious disease that attacks swine only. The disease is caused by hog cholera virus, an agent so small (1/250,000 of an inch) that it can even pass through a fine porcelain filter. How do hogs act when they get the disease? They lie around hiding in their nest, have high fevers, are extremely weak and sick all over. They have little appetite, and often stand in a thinking attitude-motionless, tail relaxed, ears hanging limp, and the head slightly lowered as if in deep thought. Very few hogs ever recover. II. How IMPORTANT Is HOG CHOLERA? Hog cholera is the most important disease of hogs in the United States today. Farmers lose millions of dollars worth of hogs from cholera each year. And the expense of annually vaccinating millions of hogs costs even more. Many foreign markets are closed to pork from the United States because of the fear of importing hog cholera. The disease is important enough so that both state and federal governments have enacted regulatory measures and classed it as a reportable disease. In addition, the United States Congress has authorized the Secretary of Agriculture to enter into a marketing agreement with the hog cholera serum-virus industry. The original act was intended to provide that there should always be enough anti-hog cholera serum on hand to safeguard against sudden widespread outbreaks of the disease. Nevertheless, stocks of antiserum are being reduced every year

Safety and efficacy of vanzacaftor–tezacaftor–deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials

Background Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing. Methods We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor–tezacaftor–deutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftor–tezacaftor–deutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftor–deutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)–tezacaftor–deutivacaftor or tezacaftor–ivacaftor active control for 4 weeks, following a 4-week tezacaftor–ivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete. Findings In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI –0·8 to 7·0) and 2·7 percentage points (–1·0 to 6·5) from baseline at week 12, respectively, versus –0·8 percentage points (–6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)–tezacaftor–deutivacaftor (n=9), vanzacaftor (10 mg)–tezacaftor–deutivacaftor (n=19), vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (−1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (−4·1 to 8·0), respectively, in sweat chloride concentration of −42·8 mmol/L (–51·7 to –34·0), −45·8 mmol/L (95% CI –51·9 to –39·7), −49·5 mmol/L (–55·9 to –43·1), and 2·3 mmol/L (−7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (−10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=18) and tezacaftor–ivacaftor (n=10) had mean changes relative to baseline (taking tezacaftor–ivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and −0·1 percentage points (−6·4 to 6·1), respectively, in sweat chloride concentration of −45·5 mmol/L (−49·7 to −41·3) and −2·6 mmol/L (−8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and −5·0 points (−16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftor–tezacaftor–deutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity. Interpretation Once-daily dosing with vanzacaftor–tezacaftor–deutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftor–tezacaftor–deutivacaftor in phase 3 clinical trials compared with elexacaftor–tezacaftor–ivacaftor. Funding Vertex Pharmaceuticals

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

WHAT YOU SHOULD KNOW ABOUT HOG CHOLERA

I. WHAT IS HOG CHOLERA? Hog cholera is a deadly, contagious disease that attacks swine only. The disease is caused by hog cholera virus, an agent so small (1/250,000 of an inch) that it can even pass through a fine porcelain filter. How do hogs act when they get the disease? They lie around hiding in their nest, have high fevers, are extremely weak and sick all over. They have little appetite, and often stand in a thinking attitude-motionless, tail relaxed, ears hanging limp, and the head slightly lowered as if in deep thought. Very few hogs ever recover. II. How IMPORTANT Is HOG CHOLERA? Hog cholera is the most important disease of hogs in the United States today. Farmers lose millions of dollars worth of hogs from cholera each year. And the expense of annually vaccinating millions of hogs costs even more. Many foreign markets are closed to pork from the United States because of the fear of importing hog cholera. The disease is important enough so that both state and federal governments have enacted regulatory measures and classed it as a reportable disease. In addition, the United States Congress has authorized the Secretary of Agriculture to enter into a marketing agreement with the hog cholera serum-virus industry. The original act was intended to provide that there should always be enough anti-hog cholera serum on hand to safeguard against sudden widespread outbreaks of the disease. Nevertheless, stocks of antiserum are being reduced every year

The comparative role of key environmental factors in determining savanna productivity and carbon fluxes: a review, with special reference to northern Australia

Terrestrial ecosystems are highly responsive to their local environments and, as such, the rate of carbon uptake both in shorter and longer timescales and different spatial scales depends on local environmental drivers. For savannas, the key environmental drivers controlling vegetation productivity are water and nutrient availability, vapour pressure deficit (VPD), solar radiation and fire. Changes in these environmental factors can modify the carbon balance of these ecosystems. Therefore, understanding the environmental drivers responsible for the patterns (temporal and spatial) and processes (photosynthesis and respiration) has become a central goal in terrestrial carbon cycle studies. Here we have reviewed the various environmental controls on the spatial and temporal patterns on savanna carbon fluxes in northern Australia. Such studies are critical in predicting the impacts of future climate change on savanna productivity and carbon storage