Surface and lightning sources of nitrogen oxides over the United States: Magnitudes, chemical evolution, and outflow

We use observations from two aircraft during the ICARTT campaign over the eastern United States and North Atlantic during summer 2004, interpreted with a global 3-D model of tropospheric chemistry (GEOS-Chem) to test current understanding of regional sources, chemical evolution, and export of NOx. The boundary layer NOx data provide top-down verification of a 50% decrease in power plant and industry NOx emissions over the eastern United States between 1999 and 2004. Observed NOx concentrations at 8–12 km altitude were 0.55 ± 0.36 ppbv, much larger than in previous U.S. aircraft campaigns (ELCHEM, SUCCESS, SONEX) though consistent with data from the NOXAR program aboard commercial aircraft. We show that regional lightning is the dominant source of this upper tropospheric NOx and increases upper tropospheric ozone by 10 ppbv. Simulating ICARTT upper tropospheric NOx observations with GEOS-Chem requires a factor of 4 increase in modeled NOx yield per flash (to 500 mol/ flash). Observed OH concentrations were a factor of 2 lower than can be explained from current photochemical models, for reasons that are unclear. A NOy-CO correlation analysis of the fraction f of North American NOx emissions vented to the free troposphere as NOy (sum of NOx and its oxidation products) shows observed f = 16 ± 10% and modeled f = 14 ± 9%, consistent with previous studies. Export to the lower free troposphere is mostly HNO3 but at higher altitudes is mostly PAN. The model successfully simulates NOy export efficiency and speciation, supporting previous model estimates of a large U.S. anthropogenic contribution to global tropospheric ozone through PAN export

The Role of Convection in Redistributing Formaldehyde to the Upper Troposphere Over North America and the North Atlantic during the Summer 2004 INTEX Campaign

Measurements of CH2O from a tunable diode laser absorption spectrometer (TDLAS) were acquired onboard the NASA DC-8 during the summer 2004 INTEX-NA (Intercontinental Chemical Transport Experiment - North America) campaign to test our understanding of convection and production mechanisms in the upper troposphere (UT, 6-12-km) over continental North America and the North Atlantic Ocean. Point-by-point comparisons with box model calculations, when MHP (CH3OOH) measurements were available for model constraint, resulted in a median CH2O measurement/model ratio of 0.91 in the UT. Multiple tracers were used to arrive at a set of UT CH2O background and perturbed air mass periods, and 46% of the TDLAS measurements fell within the latter category. At least 66% to 73% of these elevated UT observations were caused by enhanced production from CH2O precursors rather than direct transport of CH2O from the boundary layer. This distinction is important, since the effects from the former can last for over a week or more compared to one day or less in the case of convective transport of CH2O itself. In general, production of CH2O from CH4 was found to be the dominant source term, even in perturbed air masses. This was followed by production from MHP, methanol, PAN type compounds, and ketones, in descending order of their contribution. In the presence of elevated NO from lightning and potentially from the stratosphere, there was a definite trend in the CH2O discrepancy, which for the highest NO mixing ratios produced a median CH2O measurement/model ratio of 3.9 in the 10-12-km range. Discrepancies in CH2O and HO2 in the UT with NO were highly correlated and this provided further information as to the possible mechanism(s) responsible. These discrepancies with NO are consistent with additional production sources of both gases involving CH3O2 + NO reactions, most likely caused by unmeasured hydrocarbons

Impact of functional status on outcomes of simultaneous pancreas-kidney transplantation: Risks and opportunities for patient benefit

Background. The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described. Methods. We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio,(95% LCL)aHR(95%UCL)). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group. Results. KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR,(1.00)1.18(1.41)), requiring assistance (aHR,(1.06)1.31(1.60)), and disabled (aHR,(1.10)1.55(2.19)). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR,(0.26)0.48(0.88)) to 70% for patients with normal functioning (aHR,(0.26)0.30(0.34)). Conclusions. While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant

WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach?

The 2018 WHO draft guidelines on dietary saturated fatty acids and trans fatty acids recommend reducing total intake of saturated fat and replacing it with polyunsaturated and monounsaturated fatty acids. The recommendations fail to take into account considerable evidence that the health effects of saturated fat varies depending on the specific fatty acid and on the specific food source. Maintaining general advice to reduce total saturated fatty acids will work against the intentions of the guidelines and weaken their effect on chronic disease incidence and mortality. A food based translation of the recommendations for saturated fat intake would avoid unnecessary reduction or exclusion of foods that are key sources of important nutrients

Direct Measurements of the Convective Recycling of the Upper Troposphere

We present a statistical representation of the aggregate effects of deep convection on the chemistry and dynamics of the Upper Troposphere (UT) based on direct aircraft observations of the chemical composition of the UT over the Eastern United States and Canada during summer. These measurements provide new and unique observational constraints on the chemistry occurring downwind of convection and the rate at which air in the UT is recycled, previously only the province of model analyses. These results provide quantitative measures that can be used to evaluate global climate and chemistry models

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.</p

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression