Prospective multicenter randomized patient recruitment and sample collection to enable future measurements of sputum biomarkers of inflammation in an observational study of cystic fibrosis.

BACKGROUND: Biomarkers of inflammation predictive of cystic fibrosis (CF) disease outcomes would increase the power of clinical trials and contribute to better personalization of clinical assessments. A representative patient cohort would improve searching for believable, generalizable, reproducible and accurate biomarkers. METHODS: We recruited patients from Mountain West CF Consortium (MWCFC) care centers for prospective observational study of sputum biomarkers of inflammation. After informed consent, centers enrolled randomly selected patients with CF who were clinically stable sputum producers, 12 years of age and older, without previous organ transplantation. RESULTS: From December 8, 2014 through January 16, 2016, we enrolled 114 patients (53 male) with CF with continuing data collection. Baseline characteristics included mean age 27 years (SD = 12), 80% predicted forced expiratory volume in 1 s (SD = 23%), 1.0 prior year pulmonary exacerbations (SD = 1.2), home elevation 328 m (SD = 112) above sea level. Compared with other patients in the US CF Foundation Patient Registry (CFFPR) in 2014, MWCFC patients had similar distribution of sex, age, lung function, weight and rates of exacerbations, diabetes, pancreatic insufficiency, CF-related arthropathy and airway infections including methicillin-sensitive or -resistant Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, fungal and non-tuberculous Mycobacteria infections. They received CF-specific treatments at similar frequencies. CONCLUSIONS: Randomly-selected, sputum-producing patients within the MWCFC represent sputum-producing patients in the CFFPR. They have similar characteristics, lung function and frequencies of pulmonary exacerbations, microbial infections and use of CF-specific treatments. These findings will plausibly make future interpretations of quantitative measurements of inflammatory biomarkers generalizable to sputum-producing patients in the CFFPR

Genotyping within the Oxytocin Receptor (OXTR) Gene and Apathy among Persons with Alzheimer’s Disease

Apathy, defined as a disorder of motivation, is a prevalent neuropsychiatric symptom among persons with Alzheimer’s disease (AD). Variations within the Oxytocin Receptor (OXTR) Gene are hypothesized to be candidate modifiers of apathy symptoms in persons with AD. These variations are called single nucleotide polymorphisms (SNPs). The aim of this study was to amplify SNPs of interest in order to generate genotype data for 115 DNA samples collected from patients with AD. The allelic discrimination feature of real time polymerase chain reaction (RT-PCR) and primer-probe sets were used to amplify OXTR SNPs rs2268498, rs237885, rs237887, and rs237902. Genotype frequencies for each of the SNPs of interest were as follows: rs2268498 [22.6% (n=26) CC, 46.1% (n=53) CT, 23.5% (n=27) TT, 7.8% (n=9) Missing], rs237885 [21.7% (n=25) GG, 46.1% (n=53) GT, 27.0% (n=31) TT, 5.2% (n=6) Missing], rs237887 [28.7% (n=22) AA, 47.0% (n=54) AG, 18.3% (n=21) GG, 6.1% (n=7) Missing], and rs237902 [13.0% (n=15) AA, 42.6% (n=49) AG, 36.5% (n=42) GG, 7.8% (n=9) Missing]. Genotype data will be analyzed and compared to previously collected phenotype data, including apathy symptoms as measured by the Neuropsychiatric Inventory. Findings may contribute to identifying individuals with AD more at risk for apathy based on OXTR genotype

S-TrackS: A Secure Snapshot-Based Solution for Positioning and Timing

With the large-scale usage of satellite navigation, spoofing and jamming are considerable threats to civilian society. Recent developments, such as Galileo’s Open Service Navigation Message Authentication and GPS’s Chimera, mitigate these risks. However, they provide authentication of the navigation message or ranging code, but not a true position in the case of interference. In critical applications, a protected navigation service is desired, such as Galileo’s Public Regulated Service (PRS). PRS provides an access-controlled navigation service for authorized governmental users, with fully encrypted ranging codes and data channels, providing users with higher robustness against interference. The main challenge of implementing PRS on a large scale is the need to protect the cryptographic material that is required to access the PRS signals inside the receiver. For many applications, a stand-alone receiver solution is unnecessary. These applications could use a remote server for PRS. In this methodology, the end-user device has only a radio frequency front-end which sends short samples to a secure server. The (classified) signal processing is then carried out on this secure server, removing the need for the user device to protect cryptographic material. Besides decreasing the device’s security requirements and power consumption, it also allows to utilize the advantages of PRS in applications that would otherwise not be able to use PRS. In this approach the PRS usage authorization would only be required for the server operations, and not for the end-user devices. It furthermore allows for using additional processing power for unaided PRS acquisition in case of interference. Within the Netherlands, a remote server solution is developed by CGI: S-TrackS, making PRS accessible. In this paper, the application of PRS and architecture for various use cases is presented. It is shown that PRS usage based on a remote server is feasible and can increase the robustness for governmental applications

Isolation of 18 Novel Mycobacteriophages and Genomic Analyses of Krueger and Phrappuccino

Eighteen new mycobacteriophages were isolated from soil samples collected around the state of Michigan and parts of the United States. All phages were capable of infecting Mycobacterium smegmatis and were isolated through either enrichment or direct plating at 25°C. A variety of plaque morphologies were produced based on size, shape, and clarity; both lytic and temperate phages appear represented in this collection. Two mycobacteriophages, Krueger and Phrappuccino, were chosen for complete genome sequencing and comparative genomic analyses. The predominant plaque produced by Krueger at 32°C was circular and 2 mm in diameter. The predominant plaque produced by Phrappuccino at 32°C was 1 mm in diameter, and took 48 hours to appear. Complete genome sequence for Krueger revealed relationships to members of the novel Subcluster K6, while Phrappuccino was not closely related to any known phage and is currently classified as a Singleton. The genome of Krueger is 60.3 Kb, 66.5% GC, and contains 101 genes, including 1 tRNA(Lys-TTT) gene; the genome of Phrappuccino is 136.3 Kb, 67.4% GC, and contains 200 genes. While Phrappuccino is a Singleton, there is strong evidence at the morphological (Myoviridae) and genomic levels for a relationship to Cluster C phages. Despite this relationship, Phrappuccino does not carry any tRNA genes. Forty (39.6%) and thirty-six (18%) protein coding genes were assigned functions in Krueger and Phrappuccino, respectively, based on comparative analyses. A detailed analysis of the complete genome sequences and comparison with sequenced mycobacteriophages is the subject of the second semester of this yearlong course and is presented

Airway inflammation accelerates pulmonary exacerbations in cystic fibrosis

Summary: Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome