Population Mobility, Globalization, and Antimicrobial Drug Resistance

Human travel contributes to antimicrobial drug resistance around the world

Prevalence of Cardiovascular Disease and Rate of Major Adverse Cardiovascular Events in Severe Alpha-1 Antitrypsin Deficiency COPD

Aim: Alpha-1 antitrypsin deficiency is an autosomal co-dominant condition that predisposes individuals to early-onset emphysema. As with COPD, AATD-COPD is associated with pulmonary exacerbations, which impacts on overall mortality and quality of life. Though there is evidence that COPD is associated with a higher prevalence of cardiovascular disease and major adverse cardiovascular events (MACE), it is unclear if this is true for patients with AATD-COPD.Methods: Prevalence of cardiovascular disease was determined in two separate severe AATD cohorts: AlphaNet, USA and the Birmingham AATD registry, UK. All patients had preexisting lung disease. Cardiovascular disease was defined as presence of any of the following: heart failure, ischaemic heart disease, atrial fibrillation, stroke, and myocardial infarction. A Cox proportional hazards model was used to assess the impact of prior cardiovascular disease and frequent exacerbator phenotype on risk of future MACE.Results: Out of 3493 patients with severe AATD, 14.7% had prior cardiovascular disease, including stroke (2.3%), myocardial infarction (2.2%), and heart failure (2.5%). Frequent exacerbators were more likely to have preexisting cardiovascular disease compared with those with one or no exacerbations in the preceding year (63% vs 44.8%, p = 0.001). There was increased risk of future MACE in frequent exacerbators (HR 1.85, 95% CI 1.24 to 2.75), former and current smokers (HR 1.80, 95% CI 1.07 to 3.02, p = 0.026, and HR 4.04, 95% CI 1.44 to 11.32, p = 0.008, respectively), and those with prior cardiovascular disease (HR 3.81, 95% CI 2.60 to 5.58, p < 0.001).Conclusion: In severe AATD-COPD, MACE are associated with an increased exacerbation frequency, previous cardiovascular disease, and a history of smoking

Microplasma Processed Ultrathin Boron Nitride Nanosheets for Polymer Nanocomposites with Enhanced Thermal Transport Performance

This Research Article reports on the enhancement of the thermal transport properties of nanocomposite materials containing hexagonal boron nitride in poly(vinyl alcohol) through room-temperature atmospheric pressure direct-current microplasma processing. Results show that the microplasma treatment leads to exfoliation of the hexagonal boron nitride in isopropyl alcohol, reducing the number of stacks from amp;gt;30 to a few or single layers. The thermal diffusivity of the resulting nanocomposites reaches 8.5 mm(2) s(-1) times greater than blank poly(vinyl alcohol) and twice that of nanocomposites containing nonplasma treated boron nitride nanosheets. From TEM analysis, we observe much less aggregation Of the nanosheets after plasma processing along with indications of an amorphous carbon interfacial layer, which may contribute to stable dispersion of boron nitride nanosheets in the resulting plasma treated colloids.Funding Agencies|National Natural Science Foundation of China [51203135, 51173174]; Invest NI PoC award [325]; COST Action [TD1208]; Engineering &amp; Physical Sciences Research Council (EPSRC) [EP/M024938/1, EP/K022237/1]</p

Two-step human−environmental impact history for northern New Zealand linked to late-Holocene climate change

Following resolution of a long-standing debate over the timing of the initial settlement of New Zealand from Polynesia (late 13th century), a prevailing paradigm has developed that invokes rapid transformation of the landscape, principally by fire, within a few decades of the first arrivals. This model has been constructed from evidence mostly from southern and eastern regions of New Zealand, but a more complicated pattern may apply in the more humid western and northern regions where forests are more resilient to burning. We present a new pollen record from Lake Pupuke, Auckland, northern New Zealand, that charts the changing vegetation cover over the last 1000 years, before and after the arrival of people. Previous results from this site concurred with the rapid transformation model, although sampling resolution, chronology and sediment disturbance make that interpretation equivocal. Our new record is dated principally by tephrochronology together with radiocarbon dating, and includes a cryptotephra deposit identified as Kaharoa tephra, a key marker for first settlement in northern New Zealand. Its discovery and stratigraphic position below two Rangitoto-derived tephras enables a clearer picture of environmental change to be drawn. The new pollen record shows an early phase (step 1) of minor, localised forest clearance around the time of Kaharoa tephra (c. 1314 AD) followed by a later, more extensive deforestation phase (step 2) commencing at around the time of deposition of the Rangitoto tephras (c. 1400‒1450 AD). This pattern, which needs to be corroborated from other well-resolved records from northern New Zealand, concurs with an emerging hypothesis that the ‘Little Ice Age’ had a significant impact on pre-European Māori with the onset of harsher conditions causing a consolidation of populations and later environmental impact in northern New Zealand

A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Effect of Calcium Fructoborate on Systemic Inflammation and Dyslipidemia Markers for Middle-Aged People with Primary Osteoarthritis

The objective of this pilot study was to determine whether 15 days of dietary supplementation with calcium fructoborate could acutely modulate inflammatory and lipid blood markers in individuals diagnosed with primary osteoarthritis. During 2 weeks, a placebo-controlled, randomized, double-blind study was conducted on 116 subjects that were initially recruited. Seventy-two subjects started the study, being divided into four groups, and only 60 completed the study as designed. The aim was to compare the effects of calcium fructoborate to placebo on subjects diagnosed with knee primary osteoarthritis. The obtained outcomes were inflammation biomarkers (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and lipid markers (triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol). No serious adverse events were reported. The calcium fructoborate showed beneficial effect on the inflammatory markers for all groups subjected to the treatment when compared with the placebo group and slight changes in the lipid metabolism. This study suggests that short-term (2 weeks) calcium fructoborate supplementation in patients with osteoarthritis symptoms has a favorable prognosis on inflammation diseases

Can oxygen stable isotopes be used to track precipitation moisture

Variations in the isotopic composition of precipitation are determined by fractionation processes which occur during temperature- and humidity-dependent phase changes associated with evaporation and condensation. Oxygen stable isotope ratios have therefore been frequently used as a source of palaeoclimate data from a variety of proxy archives, which integrate this signal over time. Applications from ombrotrophic peatlands, where the source water used in cellulose synthesis is derived solely from precipitation, have been mostly limited to Northern Hemisphere Sphagnum-dominated bogs, with few in the Southern Hemisphere or in peatlands dominated by vascular plants. New Zealand (NZ) provides an ideal location to undertake empirical research into oxygen isotope fractionation in vascular peatlands because single taxon analysis can be easily carried out, in particular using the preserved root matrix of the restionaceous wire rush (Empodisma spp.) that forms deep Holocene peat deposits throughout the country. Furthermore, large gradients are observed in the mean isotopic composition of precipitation across NZ, caused primarily by the relative influence of different climate modes. Here, we test whether δ18O of Empodisma α-cellulose from ombrotrophic restiad peatlands in NZ can provide a methodology for developing palaeoclimate records of past precipitation δ18O. Surface plant, water and precipitation samples were taken over spatial (six sites spanning >10◦ latitude) and temporal (monthly measurements over one year) gradients. A link between the isotopic composition of root-associated water, the most likely source water for plant growth, and precipitation in both datasets was found. Back-trajectory modelling of precipitation moisture source for rain days prior to sampling showed clear seasonality in the temporal data that was reflected in root-associated water. The link between source water and plant cellulose was less clear, although mechanistic modelling predicted mean cellulose values within published error margins for both datasets. Improved physiological understanding and modelling of δ18O in restiad peatlands should enable use of this approach as a new source of palaeoclimate data to reconstruct changes in past atmospheric circulation

Identification of rare sequence variation underlying heritable pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlies most heritable forms of PAH. To identify the missing heritability we perform whole-genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses reveal significant overrepresentation of rare variants in ATP13A3, AQP1 and SOX17, and provide independent validation of a critical role for GDF2 in PAH. We demonstrate familial segregation of mutations in SOX17 and AQP1 with PAH. Mutations in GDF2, encoding a BMPR2 ligand, lead to reduced secretion from transfected cells. In addition, we identify pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings contribute new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation