Ivacaftor improves appearance of sinus disease on computerised tomography in cystic fibrosis patients with G551D mutation.

BACKGROUND: Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated. OBJECTIVE: The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease. DESIGN: Observational study. PARTICIPANTS: Twelve patients with cystic fibrosis and a G551D-CFTR mutation. METHODS: Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor. OUTCOME MEASURES: Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared. RESULTS: Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy. CONCLUSIONS: Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

KINALYZER, a computer program for reconstructing sibling groups.

A software suite KINALYZER reconstructs full-sibling groups without parental information using data from codominant marker loci such as microsatellites. KINALYZER utilizes a new algorithm for sibling reconstruction in diploid organisms based on combinatorial optimization. KINALYZER makes use of a Minimum 2-Allele Set Cover approach based on Mendelian inheritance rules and finds the smallest number of sibling groups that contain all the individuals in the sample. Also available is a 'Greedy Consensus' approach that reconstructs sibgroups using subsets of loci and finds the consensus of the partial solutions. Unlike likelihood methods for sibling reconstruction, KINALYZER does not require information about population allele frequencies and it makes no assumptions regarding the mating system of the species. KINALYZER is freely available as a web-based service.

Three-dimensional odor tracking by Nautilus pompilius.

The 'living fossil' Nautilus pompilius is thought to use olfaction as its primary sensory system during foraging, yet neither the organs responsible for olfaction nor the mechanisms or behaviors associated with odor tracking have been subjected to experimentation. Flume testing under dark conditions revealed that Nautilus could consistently detect and follow turbulent odor plumes to the source over distances up to 10 m, exhibiting two types of orientation behavior while sampling in three dimensions. The paired rhinophores were necessary for orientation behavior: when they were temporarily blocked either uni- or bilaterally, Nautilus detected odor but could not track the plume and locate the source. Animals that were tested post-blockage were able to track and locate the source. The role of the 90 thin tentacles remains enigmatic; they seemed to be able to detect odor, but they were not capable of guiding orientation behavior towards a distant odor source. Bilateral chemical sensing by rhinophores in three dimensions may have been the Umwelt of ammonites and belemnites before the evolution of complex eyes and fast locomotion in modern coleoids.