Multistatic Specular Meteor Radar Network in Peru: System Description and Initial Results

The mesosphere and lower thermosphere (MLT) region is dominated globally by dynamics at various scales: planetary waves, tides, gravity waves, and stratified turbulence. The latter two can coexist and be significant at horizontal scales less than 500 km, scales that are difficult to measure. This study presents a recently deployed multistatic specular meteor radar system, SIMONe Peru, which can be used to observe these scales. The radars are positioned at and around the Jicamarca Radio Observatory, which is located at the magnetic equator. Besides presenting preliminary results of typically reported large-scale features, like the dominant diurnal tide at low latitudes, we show results on selected days of spatially and temporally resolved winds obtained with two methods based on: (a) estimation of mean wind and their gradients (gradient method), and (b) an inverse theory with Tikhonov regularization (regularized wind field inversion method). The gradient method allows improved MLT vertical velocities and, for the first time, low-latitude wind field parameters such as horizontal divergence and relative vorticity. The regularized wind field inversion method allows the estimation of spatial structure within the observed area and has the potential to outperform the gradient method, in particular when more detections are available or when fine adaptive tuning of the regularization factor is done. SIMONe Peru adds important information at low latitudes to currently scarce MLT continuous observing capabilities. Results contribute to studies of the MLT dynamics at different scales inherently connected to lower atmospheric forcing and E-region dynamo related ionospheric variability

Primary ciliary dyskinesia: Longitudinal study of lung disease by ultrastructure defect and genotype

Rationale: In primary ciliary dyskinesia, factors leading to disease heterogeneity are poorly understood. Objectives: To describe early lung disease progression in primary ciliary dyskinesia and identify associations between ultrastructural defects and genotypes with clinical phenotype. Methods: This was a prospective, longitudinal (5 yr), multicenter, observational study. Inclusion criteria were less than 19 years at enrollment and greater than or equal to two annual study visits. Linear mixed effects models including random slope and random intercept were used to evaluate longitudinal associations between the ciliary defect group (or genotype group) and clinical features (percent predicted FEV 1 and weight and height z-scores). Measurements and Main Results: A total of 137 participants completed 732 visits. The group with absent inner dynein arm, central apparatus defects, and microtubular disorganization (IDA/CA/MTD) (n = 41) were significantly younger at diagnosis and in mixed effects models had significantly lower percent predicted FEV 1 and weight and height z-scores than the isolated outer dynein arm defect (n = 55) group. Participants with CCDC39 or CCDC40 mutations (n = 34) had lower percent predicted FEV 1 and weight and height z-scores than those with DNAH5 mutations (n = 36). For the entire cohort, percent predicted FEV 1 decline was heterogeneous with a mean (SE) decline of 0.57 (0.25) percent predicted/yr. Rate of decline was different from zero only in the IDA/MTD/CA group (mean [SE], 21.11 [0.48] percent predicted/yr; P = 0.02). Conclusions: Participants with IDA/MTD/CA defects, which included individuals with CCDC39 or CCDC40 mutations, had worse lung function and growth indices compared with those with outer dynein arm defects and DNAH5 mutations, respectively. The only group with a significant lung function decline over time were participants with IDA/MTD/CA defects

Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype

Rationale: The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. Objectives: To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. Methods: A total of 118 participants younger than 19 years old with PCD were evaluated prospectively at six centers in North America using standardized procedures for diagnostic testing, spirometry, chest computed tomography, respiratory cultures, and clinical phenotyping. Measurements and Main Results: Clinical features included neonatal respiratory distress (82%), chronic cough (99%), and chronic nasal congestion (97%). There were no differences in clinical features or respiratory pathogens in subjects with outer dynein arm (ODA) defects (ODA alone; n = 54) and ODA plus inner dynein arm (IDA) defects (ODA 1 IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/ CA/MTD; n = 40). Median FEV 1 was worse in the IDA/CA/MTD group (72% predicted) versus the combined ODA groups (92% predicted; P = 0.003). Median body mass index was lower in the IDA/ CA/MTD group (46th percentile) versus the ODA groups (70th percentile; P = 0.003). For all 118 subjects, median number of lobes with bronchiectasis was three and alveolar consolidation was two. However, the 5- to 11-year-old IDA/CA/MTD group had more lobes of bronchiectasis (median, 5; P = 0.0008) and consolidation (median, 3; P = 0.0001) compared with the ODA groups (median, 3 and 2, respectively). Similar findings were observed when limited to participants with biallelic mutations. Conclusions: Lung disease was heterogeneous across all ultrastructural and genotype groups, but worse in those with IDA/ CA/MTD ultrastructural defects, most of whom had biallelic mutations in CCDC39 or CCDC40

Diagnosis of primary ciliary dyskinesia: An official American thoracic society clinical practice guideline

Background: This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD). Target Audience: Clinicians investigating adult and pediatric patients for possible PCD. Methods: Systematic reviews and, when appropriate, meta-Analyses were conducted to summarize all available evidence pertinent to our clinical questions. Evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for diagnosis and discussed by amultidisciplinary panelwith expertise in PCD. Predetermined conflict-of-interest management strategies were applied, and recommendations were formulated, written, and graded exclusively by the nonconflicted panelists. Three conflicted individuals were also prohibited from writing, editing, or providing feedback on the relevant sections of the manuscript. Results: After considering diagnostic test accuracy, confidence in the estimates for each diagnostic test, relative importance of test results studied, desirable and undesirable direct consequences of each diagnostic test, downstream consequences of each diagnostic test result, patient values and preferences, costs, feasibility, acceptability, and implications for health equity, the panel made recommendations for or against the use of specific diagnostic tests as compared with using the current reference standard (transmission electron microscopy and/or genetic testing) for the diagnosis of PCD. Conclusions: The panel formulated and provided a rationale for the direction as well as for the strength of each recommendation to establish the diagnosis of PCD

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia

Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. Objectives: Touse a standard protocol formeasuringnNOtoestablishadiseasespecific cutoff value at one site, and then validate at six other sites. Methods: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. Measurements and Main Results: At the lead site, nNO values in PCD (mean6standard deviation, 20.7624.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 6 118.8; 125.5-867.0 nl/min), asthma (267.8 6 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 6 87.1; 109.7-449.1 nl/min); however, therewas overlapwith cystic fibrosis (134.0673.5; 15.6-386.1 nl/min). The disease-specific nNOcutoff valuewas defined at 77 nl/minute (sensitivity, 0.98; specificity, .0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. Conclusions: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD. Objectives: To identify disease-causingmutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD. Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis. Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P , 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEV1), compared with 75 age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.16Hz at 258C), but an abnormal, circular beat pattern. Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function

Connectivity, land use, and fish presence influence smooth newt (Lissotriton vulgaris) occurrence and abundance in an urban landscape

Introduction: Urban areas are challenging environments for wetland species with complex habitat requirements and life cycles. However, even semiaquatic species, representing such complex wetland groups, can be provided with adequate conditions through thorough understanding of their habitat requirements coupled with comprehensive wetland management. Methods: We studied the occurrence and abundance of the smooth newt (Lissotriton vulgaris), a widely distributed amphibian, in an urban landscape in metropolitan Helsinki, Finland. We classified 50 randomly selected urban wetlands based on their connectivity by applying isolation scores counted using principal component analysis (PCA) and measured the occurrence and abundance of smooth newts in these locations. Results: Our analyses showed well-connected wetland sites to differ significantly in smooth newt occurrence from both isolated and partially connected sites. Additionally, smooth newt abundance in well-connected wetlands differed from isolated sites. A PCA model with residential buildings (negative effect) and aquatic vegetation (positive effect) best explained smooth newt occurrence and total and male abundance, and female newt occurrence was best explained by a model also incorporating forest and natural open areas. Predation pressure by fish negatively influenced both smooth newt occurrence and abundance. Discussion: Tighter networks of constructed wetlands and stricter management guidelines for urban wetland planning and fish community management could increase the suitable habitat for smooth newts in urban landscapes. Managing such areas for the common smooth newt offers potential broad benefits to the conservation of other semiaquatic amphibians and reptiles in urban wetlands and to urban wetland biodiversity in general. Our results show that smooth newt presence may indicate sustained wetland connectivity in an urban landscape and could even be used to signal successful urban planning.Peer reviewe

Lung matrix and vascular remodeling in mechanically ventilated elastin haplo-insufficient (<em>Eln^+/-</em>) newborn mice.

Elastin plays a pivotal role in lung development. We therefore queried if elastin haplo-insufficient newborn mice (Eln(+/-)) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. As mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haplo-insufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5d-old wild-type (Eln(+/+)) and Eln(+/-) littermates at baseline, and after MV with air for 8-24h. Lungs of unventilated Eln(+/-) mice contained ~50% less elastin and ~100% more collagen-1 and lysyl oxidase compared to Eln(+/+) pups. Eln(+/-) lungs contained fewer capillaries than Eln(+/+) lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln(+/+) neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln(+/-) mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln(+/-) than in Eln(+/+) pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln(+/-) compared to Eln(+/+) mice, was similar in both groups after MV. These results suggest that elastin haplo-insufficiency adversely impacts pulmonary angiogenesis, and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln(+/+) and Eln(+/-) mice. Paucity of lung capillaries in Eln(+/-) newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln(+/-) mice