Ambient air pollution and emergency department visits and hospitalisation for cardiac arrest: a population-based case-crossover study in Reykjavik, Iceland.

OBJECTIVES: To assess the association between traffic-related ambient air pollution and emergency hospital visits for cardiac arrest. DESIGN: Case-crossover design was used with a lag time to 4 days. SETTING: The Reykjavik capital area and the study population was the inhabitants 18 years and older identified by encrypted personal identification numbers and zip codes. PARTICIPANTS AND EXPOSURE: Cases were those with emergency visits to Landspitali University Hospital during the period 2006-2017 and who were given the primary discharge diagnosis of cardiac arrest according to the International Classification of Diseases 10th edition (ICD-10) code I46. The pollutants were nitrogen dioxide (NO2), particulate matter with aerodynamic diameter less than 10 µm (PM10), particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5) and sulfur dioxide (SO2) with adjustment for hydrogen sulfide (H2S), temperature and relative humidity. MAIN OUTCOME MEASURE: OR and 95% CIs per 10 µg/m3 increase in concentration of pollutants. RESULTS: The 24-hour mean NO2 was 20.7 µg/m3, mean PM10 was 20.5 µg/m3, mean PM2.5 was 12.5 µg/m3 and mean SO2 was 2.5 µg/m3. PM10 level was positively associated with the number of emergency hospital visits (n=453) for cardiac arrest. Each 10 µg/m3 increase in PM10 was associated with increased risk of cardiac arrest (ICD-10: I46), OR 1.096 (95% CI 1.033 to 1.162) on lag 2, OR 1.118 (95% CI 1.031 to 1.212) on lag 0-2, OR 1.150 (95% CI 1.050 to 1.261) on lag 0-3 and OR 1.168 (95% CI 1.054 to 1.295) on lag 0-4. Significant associations were shown between exposure to PM10 on lag 2 and lag 0-2 and increased risk of cardiac arrest in the age, gender and season strata. CONCLUSIONS: A new endpoint was used for the first time in this study: cardiac arrest (ICD-10 code: I46) according to hospital discharge registry. Short-term increase in PM10 concentrations was associated with cardiac arrest. Future ecological studies of this type and their related discussions should perhaps concentrate more on precisely defined endpoints.

Ambient nitrogen dioxide is associated with emergency hospital visits for atrial fibrillation: a population-based case-crossover study in Reykjavik, Iceland.

BACKGROUND: In Iceland air quality is generally good; however, previous studies indicate that there is an association between air pollution in Reykjavik and adverse health effects as measured by dispensing of medications, mortality, and increase in health care utilisation. The aim was to study the association between traffic-related ambient air pollution in the Reykjavik capital area and emergency hospital visits for heart diseases and particularly atrial fibrillation and flutter (AF). METHODS: A multivariate time-stratified case-crossover design was used to study the association. Cases were those patients aged 18 years or older living in the Reykjavik capital area during the study period, 2006-2017, who made emergency visits to Landspitali University Hospital for heart diseases. In this population-based study, the primary discharge diagnoses were registered according to International Classification of Diseases, 10th edition (ICD-10). The pollutants studied were NO2, PM10, PM2.5, and SO2, with adjustment for H2S, temperature, and relative humidity. The 24-h mean of pollutants was used with lag 0 to lag 4. RESULTS: During the study period 9536 cases of AF were identified. The 24-h mean NO2 was 20.7 µg/m3. Each 10 µg/m3 increase in NO2 was associated with increased risk of heart diseases (ICD-10: I20-I25, I44-I50), odds ratio (OR) 1.023 (95% CI 1.012-1.034) at lag 0. Each 10 µg/m3 increase in NO2 was associated with an increased risk of AF (ICD-10: I48) on the same day, OR 1.030 (95% CI: 1.011-1.049). Females were at higher risk for AF, OR 1.051 (95% CI 1.019-1.083) at lag 0, and OR 1.050 (95% CI 1.019-1.083) at lag 1. Females aged younger than 71 years had even higher risk for AF, OR 1.077 (95% CI: 1.025-1.131) at lag 0. Significant associations were found for other pollutants and emergency hospital visits, but they were weaker and did not show a discernable pattern. CONCLUSIONS: Short-term increase in NO2 concentrations was associated with heart diseases, more precisely with AF. The associations were stronger among females, and among females at younger age. This is the first study in Iceland that finds an association between air pollution and cardiac arrhythmias, so the results should be interpreted with caution.

Accuracy evaluation of five blood glucose monitoring systems: the North American comparator trial.

BACKGROUND: This study evaluated differences in accuracy between the CONTOUR® NEXT EZ (EZ) blood glucose monitoring system (BGMS) and four other BGMSs [ACCU-CHEK® Aviva (ACAP), FreeStyle Freedom Lite® (FFL), ONE TOUCH® Ultra®2 (OTU2), and TRUEtrack® (TT)]. METHODS: Up to three capillary blood samples (N = 393) were collected from 146 subjects with and without diabetes. One sample per subject was tested with fresh (natural) blood; the other samples were glycolyzed to lower blood glucose to <70 mg/dl. Meter results were compared with results from plasma from the same sample tested on a Yellow Springs Instruments (YSI) 2300 STAT PlusTM glucose analyzer. Blood glucose monitoring system accuracy was compared using mean absolute relative difference (MARD; from laboratory reference method results) and other analyses. Separate analyses on fresh (natural) samples only were conducted to determine potential effects of glycolysis on MARD values of systems utilizing glucose-oxidase-based test strip chemistry. RESULTS: Across the tested glucose range, the EZ had the lowest MARD of 4.7%; the ACAP, FFL, OTU2, and TT had MARD values of 6.3%, 18.3%, 23.4%, and 26.2%, respectively. For samples with glucose concentrations <70 mg/dl, the EZ had the lowest MARD (0.65%), compared with the ACAP (2.5%), FFL (18.3%), OTU2 (22.4%), and TT (33.2%) systems. CONCLUSIONS: The EZ had the lowest MARD across the tested glucose ranges when compared with four other BGMSs when all samples were analyzed as well as when natural samples only were analyzed.

Accuracy of the CONTOUR® blood glucose monitoring system.

OBJECTIVE: The aim of the study was to assess the accuracy of the CONTOUR® blood glucose monitoring system (BGMS) according to the International Organization for Standardization's International Standard 15197 (ISO 15197:2003) guidelines and to more stringent criteria. METHOD: Finger stick blood samples from 105 subjects with diabetes (25 with type 1, 77 with type 2, and 3 with type unknown) were tested using the CONTOUR BGMS and YSI glucose analyzer. RESULTS: 99.3% of results were within ISO 15197:2003 criteria (±15 mg/dl of YSI results at glucose concentrations <75 mg/dl and ±20% at glucose concentrations ≥75 mg/dl). Additionally, 96.7% of results were accurate according to more stringent criteria (±15 mg/dl of YSI results for glucose concentrations <100 mg/dl and ±15% for glucose concentrations ≥100 mg/dl). Error grid analysis showed that 99.3% and 0.7% of results were within zones A and B, respectively. CONCLUSION: The CONTOUR BGMS exceeded both the minimum acceptable accuracy based on ISO 15197:2003 and the more stringent accuracy criteria.

Reproducibility and accuracy of body composition assessments in mice by dual energy x-ray absorptiometry and time domain nuclear magnetic resonance.

OBJECTIVE: To assess the accuracy and reproducibility of dual-energy absorptiometry (DXA; PIXImus(™)) and time domain nuclear magnetic resonance (TD-NMR; Bruker Optics) for the measurement of body composition of lean and obese mice. SUBJECTS AND MEASUREMENTS: Thirty lean and obese mice (body weight range 19-67 g) were studied. Coefficients of variation for repeated (x 4) DXA and NMR scans of mice were calculated to assess reproducibility. Accuracy was assessed by comparing DXA and NMR results of ten mice to chemical carcass analyses. Accuracy of the respective techniques was also assessed by comparing DXA and NMR results obtained with ground meat samples to chemical analyses. Repeated scans of 10-25 gram samples were performed to test the sensitivity of the DXA and NMR methods to variation in sample mass. RESULTS: In mice, DXA and NMR reproducibility measures were similar for fat tissue mass (FTM) (DXA coefficient of variation [CV]=2.3%; and NMR CV=2.8%) (P=0.47), while reproducibility of lean tissue mass (LTM) estimates were better for DXA (1.0%) than NMR (2.2%) (

Presence/absence polymorphism for alternative pathogenicity islands in Pseudomonas viridiflava, a pathogen of Arabidopsis.

The contribution of arms race dynamics to plant-pathogen coevolution has been called into question by the presence of balanced polymorphisms in resistance genes of Arabidopsis thaliana, but less is known about the pathogen side of the interaction. Here we investigate structural polymorphism in pathogenicity islands (PAIs) in Pseudomonas viridiflava, a prevalent bacterial pathogen of A. thaliana. PAIs encode the type III secretion system along with its effectors and are essential for pathogen recognition in plants. P. viridiflava harbors two structurally distinct and highly diverged PAI paralogs (T- and S-PAI) that are integrated in different chromosome locations in the P. viridiflava genome. Both PAIs are segregating as presence/absence polymorphisms such that only one PAI ([T-PAI, nablaS-PAI] and [nablaT-PAI, S-PAI]) is present in any individual cell. A worldwide population survey identified no isolate with neither or both PAI. T-PAI and S-PAI genotypes exhibit virulence differences and a host-specificity tradeoff. Orthologs of each PAI can be found in conserved syntenic locations in other Pseudomonas species, indicating vertical phylogenetic transmission in this genus. Molecular evolutionary analysis of PAI sequences also argues against "recent" horizontal transfer. Spikes in nucleotide divergence in flanking regions of PAI and nabla-PAI alleles suggest that the dual PAI polymorphism has been maintained in this species under some form of balancing selection. Virulence differences and host specificities are hypothesized to be responsible for the maintenance of the dual PAI system in this bacterial pathogen.

Linkage disequilibrium mapping of Arabidopsis CRY2 flowering time alleles.

The selfing plant Arabidopsis thaliana has been proposed to be well suited for linkage disequilibrium (LD) mapping as a means of identifying genes underlying natural trait variation. Here we apply LD mapping to examine haplotype variation in the genomic region of the photoperiod receptor CRYPTOCHROME2 and associated flowering time variation. CRY2 DNA sequences reveal strong LD and the existence of two highly differentiated haplogroups (A and B) across the gene; in addition, a haplotype possessing a radical glutamine-to-serine replacement (AS) occurs within the more common haplogroup. Growth chamber and field experiments using an unstratified population of 95 ecotypes indicate that under short-day photoperiod, the AS and B haplogroups are both highly significantly associated with early flowering. Data from six genes flanking CRY2 indicate that these haplogroups are limited to an approximately 65-kb genomic region around CRY2. Whereas the B haplogroup cannot be delimited to <16 kb around CRY2, the AS haplogroup is characterized almost exclusively by the nucleotide polymorphisms directly associated with the serine replacement in CRY2; this finding strongly suggests that the serine substitution is directly responsible for the AS early flowering phenotype. This study demonstrates the utility of LD mapping for elucidating the genetic basis of natural, ecologically relevant variation in Arabidopsis.

A latitudinal cline in flowering time in Arabidopsis thaliana modulated by the flowering time gene FRIGIDA.

A latitudinal cline in flowering time in accessions of Arabidopsis thaliana has been widely predicted because the environmental cues that promote flowering vary systematically with latitude, but evidence for such clines has been lacking. Here, we report evidence of a significant latitudinal cline in flowering time among 70 Northern European and Mediterranean ecotypes when grown under ecologically realistic conditions in a common garden environment. The detected cline, however, is found only in ecotypes with alleles of the flowering time gene FRIGIDA (FRI) that lack major deletions that would disrupt protein function, whereas there is no relationship between flowering time and latitude of origin among accessions with FRI alleles containing such deletions. Analysis of climatological data suggests that late flowering in accessions with putatively functional FRI was associated with reduced January precipitation at the site of origin, consistent with previous reports of a positive genetic correlation between water use efficiency and flowering time in Arabidopsis, and the pleiotropic effects of FRI of increasing water use efficiency. In accessions collected from Southern latitudes, we detected that putatively functional FRI alleles were associated with accelerated flowering relative to accessions with nonfunctional FRI under the winter conditions of our experiment. These results suggest that the ecological function of the vernalization requirement conferred by FRI differs across latitudes. More generally, our results indicate that by combining ecological and molecular genetic data, it is possible to understand the forces acting on life history transitions at the level of specific loci.

Heterogeneous selection at specific loci in natural environments in Arabidopsis thaliana.

Genetic variation for quantitative traits is often greater than that expected to be maintained by mutation in the face of purifying natural selection. One possible explanation for this observed variation is the action of heterogeneous natural selection in the wild. Here we report that selection on quantitative trait loci (QTL) for fitness traits in the model plant species Arabidopsis thaliana differs among natural ecological settings and genetic backgrounds. At one QTL, the allele that enhanced the viability of fall-germinating seedlings in North Carolina reduced the fecundity of spring-germinating seedlings in Rhode Island. Several other QTL experienced strong directional selection, but only in one site and seasonal cohort. Thus, different loci were exposed to selection in different natural environments. Selection on allelic variation also depended upon the genetic background. The allelic fitness effects of two QTL reversed direction depending on the genotype at the other locus. Moreover, alternative alleles at each of these loci caused reversals in the allelic fitness effects of a QTL closely linked to TFL1, a candidate developmental gene displaying nucleotide sequence polymorphism consistent with balancing selection. Thus, both environmental heterogeneity and epistatic selection may maintain genetic variation for fitness in wild plant species.

Genotype-environment interactions at quantitative trait loci affecting inflorescence development in Arabidopsis thaliana.

Phenotypic plasticity and genotype-environment interactions (GEI) play a prominent role in plant morphological diversity and in the potential functional capacities of plant life-history traits. The genetic basis of plasticity and GEI, however, is poorly understood in most organisms. In this report, inflorescence development patterns in Arabidopsis thaliana were examined under different, ecologically relevant photoperiod environments for two recombinant inbred mapping populations (Ler x Col and Cvi x Ler) using a combination of quantitative genetics and quantitative trait locus (QTL) mapping. Plasticity and GEI were regularly observed for the majority of 13 inflorescence traits. These observations can be attributable (at least partly) to variable effects of specific QTL. Pooled across traits, 12/44 (27.3%) and 32/62 (51.6%) of QTL exhibited significant QTL x environment interactions in the Ler x Col and Cvi x Ler lines, respectively. These interactions were attributable to changes in magnitude of effect of QTL more often than to changes in rank order (sign) of effect. Multiple QTL x environment interactions (in Cvi x Ler) clustered in two genomic regions on chromosomes 1 and 5, indicating a disproportionate contribution of these regions to the phenotypic patterns observed. High-resolution mapping will be necessary to distinguish between the alternative explanations of pleiotropy and tight linkage among multiple genes.

Quantitative trait loci for inflorescence development in Arabidopsis thaliana.

Variation in inflorescence development patterns is a central factor in the evolutionary ecology of plants. The genetic architectures of 13 traits associated with inflorescence developmental timing, architecture, rosette morphology, and fitness were investigated in Arabidopsis thaliana, a model plant system. There is substantial naturally occurring genetic variation for inflorescence development traits, with broad sense heritabilities computed from 21 Arabidopsis ecotypes ranging from 0.134 to 0.772. Genetic correlations are significant for most (64/78) pairs of traits, suggesting either pleiotropy or tight linkage among loci. Quantitative trait locus (QTL) mapping indicates 47 and 63 QTL for inflorescence developmental traits in Ler x Col and Cvi x Ler recombinant inbred mapping populations, respectively. Several QTL associated with different developmental traits map to the same Arabidopsis chromosomal regions, in agreement with the strong genetic correlations observed. Epistasis among QTL was observed only in the Cvi x Ler population, and only between regions on chromosomes 1 and 5. Examination of the completed Arabidopsis genome sequence in three QTL regions revealed between 375 and 783 genes per region. Previously identified flowering time, inflorescence architecture, floral meristem identity, and hormone signaling genes represent some of the many candidate genes in these regions.

Novel loci control variation in reproductive timing in Arabidopsis thaliana in natural environments.

Molecular biologists are rapidly characterizing the genetic basis of flowering in model species such as Arabidopsis thaliana. However, it is not clear how the developmental pathways identified in controlled environments contribute to variation in reproductive timing in natural ecological settings. Here we report the first study of quantitative trait loci (QTL) for date of bolting (the transition from vegetative to reproductive growth) in A. thaliana in natural seasonal field environments and compare the results with those obtained under typical growth-chamber conditions. Two QTL specific to long days in the chamber were expressed only in spring-germinating cohorts in the field, and two loci specific to short days in the chamber were expressed only in fall-germinating cohorts, suggesting differential involvement of the photoperiod pathway in different seasonal environments. However, several other photoperiod-specific QTL with large effects in controlled conditions were undetectable in natural environments, indicating that expression of allelic variation at these loci was overridden by environmental factors specific to the field. Moreover, a substantial number of QTL with major effects on bolting date in one or more field environments were undetectable under controlled environment conditions. These novel loci suggest the involvement of additional genes in the transition to flowering under ecologically relevant conditions.