Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), ...nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960–2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr−1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr−1. Over the period 2013–2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000–2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m−2 (5–95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m−2), CO2 (34.3 mW m−2), and NOx (17.5 mW m−2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m−2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.
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•Global aviation warms Earth's surface through both CO2 and net non-CO2 contributions.•Global aviation contributes a few percent to anthropogenic radiative forcing.•Non-CO2 impacts comprise about 2/3 of the net radiative forcing.•Comprehensive and quantitative calculations of aviation effects are presented.•Data are made available to analyze past, present and future aviation climate forcing.
BACKGROUND: Pro-inflammatory chemokines that attract and cytokines that activate immune cells contribute to normal physiological homeostasis in the female reproductive tract, and are needed to deal ...effectively with potential pathogenic microbes. Mucosal epithelial cells are capable of producing these factors that communicate with cells of the innate and adaptive immune systems. METHODS: Epithelial cells from Fallopian tube, endometrium and endocervix were isolated and grown to high transepithelial resistance in cell inserts from seven patients who had hysterectomies. Interleukin (IL)-8, IL-6, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), granulocyte–macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-α (TNF-α) and macrophage inflammatory peptide-1β (MIP-1β) were assessed by Luminex bead analysis or enzyme-linked immunosorbent assay (ELISA) in epithelial cell conditioned media from the apical and basolateral compartments. RESULTS: With the exception of MCP-1, the seven chemokines/cytokines constitutively produced by the polarized epithelial cells were preferentially secreted apically. A concentration pattern was found in all cases, with IL-8 and IL-6 produced in the greatest quantity. CONCLUSIONS: The concentrations of IL-8, IL-6, G-CSF and MCP-1 are similar to the levels found in reproductive tract fluids of patients with infection. The constitutive secretion and compartmentalization of large quantities of bioactive chemokines and cytokines provide additional evidence for the role of epithelial cells as gatekeepers of innate immune protection in the female reproductive tract.
Airborne observations of fluorescent aerosol were made aboard an airship during CloudLab, a series of flights that took place in September and October of 2013 and covered a wideband of longitude ...across the continental U.S. between Florida and California and between 28 and 37 N latitudes. Sampling occurred from near the surface to 1000 m above the ground. A Wideband Integrated Bioaerosol Sensor (WIBS‐4) measured average concentrations of supermicron fluorescent particles aloft (1 µm to 10 µm), revealing number concentrations ranging from 2.1 ± 0.8 to 8.7 ± 2.2 × 104 particles m−3 and representing up to 24% of total supermicron particle number. We observed distinct variations in size distributions and fluorescent characteristics in different regions, and attribute these to geographically diverse bioaerosol. Fluorescent aerosol detected in the east is largely consistent with mold spores observed in a laboratory setting, while a shift to larger sizes associated with different fluorescent patterns is observed in the west. Fluorescent bioaerosol loadings in the desert west were as high as those near the Gulf of Mexico, suggesting that bioaerosol is a substantial component of supermicron aerosol both in humid and arid environments. The observations are compared to model fungal and bacterial loading predictions, and good agreement in both particle size and concentrations is observed in the east. In the west, the model underestimated observed concentrations by a factor between 2 and 4 and the prescribed particle sizes are smaller than the observed fluorescent aerosol. A classification scheme for use with WIBS data is also presented.
Key Points
Fluorescent supermicron aerosol loads are reported across the southern U.S.
Regional variations in fluorescent behavior and particle size are observed
Comparison to modeled emissions shows an underestimate in the west
Childhood stroke results in long-term, multifaceted difficulties, affecting motor, cognitive, communication, and behavioral domains of function which impact on participation and quality of life. The ...Childhood Stroke Consensus Rehabilitation Guideline was developed to improve the care of children with stroke by providing health professionals with recommendations to assist in their rehabilitative treatment. Clinical questions were formulated to inform systematic database searches from 2001 to 2016, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grade of Recommendation, Assessment, Development and Evaluation system was used to grade evidence as strong or weak. Where evidence was inadequate or absent, a modified Delphi consensus process was used to develop consensus-based recommendations. The guideline provides 56 recommendations (1 evidence-based recommendation and 55 consensus recommendations). These relate to the framework of rehabilitation service delivery as well as domain-specific rehabilitation treatment strategies for each domain of function. It is anticipated that this guideline will provide health professions with recommendations to improve the subacute care of children with stroke both in Australia and internationally.
Summary
‘Days alive and at home’ is a validated measure that estimates the time spent at home, defined as the place of residence before admission to hospital. We evaluated this metric in older adults ...after hip fracture surgery and assessed two follow‐up durations, 30 and 90 days. Patients aged ≥ 70 years who underwent hip fracture surgery were identified retrospectively via hospital admission and government mortality records. Patients who successfully returned home and were still alive within 90 days of surgery were distinguished from those who were not. Regression models were used to examine which variables were associated with failure to return home and number of days at home among those who did return, within 90 days of surgery. We analysed the records of 825 patients. Median (IQR range) number of days at home within 90 days (n = 788) was 54 (0–76 0–88) days and within 30 days (n = 797) it was 2 (0–21 0–28) days. Out of these, 274 (35%) patients did not return home within 90 days and 374 (47%) within 30 days after surgery. Known peri‐operative risk‐factors such as older age, pre‐operative anaemia and postoperative acute renal impairment were associated with failure to return home. This study supports days alive and at home as a useful patient‐centred outcome measure in older adults after hip fracture surgery. We recommend that this metric should be used in clinical trials and measured at 90, rather than 30, postoperative days. As nearly half of this patient population did not return home within 30 days, the shorter time‐period catches fewer meaningful events.
Summary
The objective of this study was to examine the expression of toll‐like receptors (TLRs) by the uterine epithelial cell line ECC‐1 and to determine if stimulation of the expressed TLRs induces ...changes in cytokine and/or chemokine secretion. The expression of TLR1 to TLR9 by ECC‐1 cells was demonstrated by reverse transcription polymerase chain reaction, with only TLR10 not being expressed. Stimulation of ECC‐1 cells using agonists to TLR2, TLR4 and TLR5 induced the expression of the chemokines interleukin‐8 (IL‐8) and monocyte chemotactic protein‐1 (MCP‐1), as well as the pro‐inflammatory cytokine IL‐6, and occurred in a dose‐dependent manner. In response to zymosan and flagellin, pathogen‐associated molecular patterns (PAMP) that are recognized by TLR2 and TLR5 respectively, ECC‐1 cells secreted significantly more IL‐8, MCP‐1 and IL‐6 than in response to other TLR agonists. In contrast, agonists to TLR3, TLR7, and TLR9 had no effect on the secretion of the 13 cytokines or chemokines analysed. These results indicate that uterine epithelial cells are important sentinels of the innate immune system. Further it indicates that all but one of the known TLRs are expressed by ECC‐1 cells and that stimulation through specific TLRs mediates changes in the expression of key chemokines and pro‐inflammatory cytokines that aid in the defence of the uterus against potential pathogens.
The objectives of this study were 1) to compare the effects of a ME () or a NE () system for rationing ewes during late gestation on ewe and progeny performance and 2) to investigate incremental ...increases in NE allocation above 100% of recommendation during late gestation on ewe and progeny performance. Fifty-two twin-bearing ewes ( = 13 per treatment) were rationed to either 100% of recommended ME requirements (100% ME) or 100, 110, or 120% of recommended NE requirements (100% NE, 110% NE, and 120% NE) from d 112 of gestation to parturition. Mean energy intake, measured as ME and NE, from Day 112 of gestation to parturition was higher in all NE treatments compared with 100% ME ewes ( = 0.01). Ewes offered the 3 NE treatments had a higher live weight at parturition compared with 100% ME ewes ( = 0.02), with 100% NE and 120% NE ewes still being heavier than 100% ME ewes at 35 d postpartum ( = 0.02). Increasing NE allowance resulted in a linear decrease in the level of BCS loss prepartum ( = 0.01) and a linear increase in the level of BCS loss postpartum ( = 0.01). There was no difference observed between any of the treatments in total colostrum produced to 18 h postpartum ( = 0.29) or in total colostrum intake to 18 h postpartum ( = 0.27). Increasing maternal NE allowance led to a linear increase in lamb serum IgG concentration at 24 h postpartum ( = 0.03). The estimated milk production of 120% NE ewes tended to be higher than all other treatments at wk 6 of lactation ( = 0.08). Colostral SFA levels from 100% ME ewes was lower than that of all 3 NE treatments ( = 0.01), and unsaturated fatty acid (UFA) levels in colostrum of the 100% ME ewes were lower than those of the 100% NE ewes ( = 0.01). Cumulative levels of milk SFA, UFA, and MUFA did not differ between treatments ( = 0.19). Lamb growth rates during the first 5 wk postpartum were unaffected by treatment ( = 0.18) as were days to slaughter ( = 0.34). It can be concluded that both ME and NE systems used in this study are appropriate for formulating ewe diets during late gestation. Increasing NE allocation above 100% altered the pattern of body reserve mobilization during late gestation and early lactation without observed variations in lamb performance during this time.
Summary
Aims: The aim of the study was to explore the long‐term effect of allopurinol on mortality and cardiovascular hospitalisations in heart failure (HF) patients.
Methods: This is a ...population‐based cohort study using a record‐linkage database in Tayside, Scotland. A total of 4785 HF patients (4260 non‐users, 267 incident users and 258 prevalent users) were studied between 1993 and 2002.
Results: Compared with non‐users, low‐dose users in the incident group had a significant increased risk of all‐cause mortality, cardiovascular mortality and cardiovascular recurrence (adjusted HR, 1.60, 95%CI 1.26–2.03; 1.70, 1.29–2.23 and 1.44, 1.01–2.07). For the prevalent users, the adjusted HR were 1.27, 0.98–1.64; 1.43, 1.07–1.90 and 1.27, 0.91–1.76 respectively. There was no increased risk of outcome for high‐dose users when compared with non‐users (adjusted HR, 1.18, 0.84–1.66; 1.14, 0.76–1.71 and 1.36, 0.88–2.10 for the incident users, and 0.86, 0.64–1.15; 0.90, 0.64–1.26; and 1.27, 0.93–1.74 for the prevalent users respectively). High‐dose allopurinol was associated with reduced risk of all‐course mortality for prevalent users when compared with low‐dose (adjusted HR 0.65, 95%CI 0.42–0.99).
Conclusions: The prevalent high‐dose allopurinol use had a lower risk of mortality than the prevalent low‐dose use suggesting that allopurinol may be of benefit in HF patients.
Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable ...from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended.
This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic.
Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance.
Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test.
These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses.
Genetic white matter disorders are genetically and phenotypically heterogeneous. Deep phenotyping together with a range of genomic technologies underpin the identification of causes of unclassified white matter disease. A molecular diagnosis is essential for prognostication, appropriate management, and accurate reproductive counseling.
Summary
Background Coeliac disease is more prevalent than was previously thought. The association between coeliac disease and cardiovascular outcome is not clear.
Aim To investigate whether coeliac ...disease patients have an increased risk of cardiovascular events.
Methods A community‐based cohort study using a record‐linkage database. Three hundred and sixty‐seven coeliac patients identified by a positive antiendomysial antibody test or a diagnosis with small bowel biopsy, and 5537 subjects who were tested and had a negative coeliac immunology, were included in the study.
Results The crude rates of cardiovascular events were 9.5 per 1000 person‐years (95% CI: 4.4–14.6) in the coeliac cohort and 8.9 per 1000 person‐years (95% CI: 7.6–10.3) in the antiendomysial antibody‐negative cohort. Compared with the antiendomysial antibody‐negative cohort, the adjusted relative risk of cardiovascular events for coeliac cohort was 1.9 (95% CI: 1.00–3.60). When we excluded patients who had previous hospitalization for cardiovascular disease, the adjusted relative risk was 2.5 (95% CI: 1.22–5.01). The use of any cardiovascular drugs prior to and after entry to the study were 36% and 29% for the coeliac cohort (P = 0.05), and 34% and 26% for the antiendomysial antibody‐negative cohort (P < 0.01).
Conclusion Our findings suggest that coeliac disease seems to be associated with an increased risk of cardiovascular outcome.
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