Infant microbes and metabolites point to childhood neurodevelopmental disorders.

This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.

Spontaneous dark formation of OH radicals at the interface of aqueous atmospheric droplets.

Hydroxyl radical (OH) is a key oxidant that triggers atmospheric oxidation chemistry in both gas and aqueous phases. The current understanding of its aqueous sources is mainly based on known bulk (photo)chemical processes, uptake from gaseous OH, or related to interfacial O3 and NO3 radical-driven chemistry. Here, we present experimental evidence that OH radicals are spontaneously produced at the air-water interface of aqueous droplets in the dark and the absence of known precursors, possibly due to the strong electric field that forms at such interfaces. The measured OH production rates in atmospherically relevant droplets are comparable to or significantly higher than those from known aqueous bulk sources, especially in the dark. As aqueous droplets are ubiquitous in the troposphere, this interfacial source of OH radicals should significantly impact atmospheric multiphase oxidation chemistry, with substantial implications on air quality, climate, and health.

Unveiling the underestimated direct emissions of nitrous acid (HONO).

Gaseous nitrous acid (HONO) is a critical source of hydroxyl radicals (OH) in the troposphere. While both direct and secondary sources contribute to atmospheric HONO, direct emissions have traditionally been considered minor contributors. In this study, we developed δ15N and δ18O isotopic fingerprints to identify six direct HONO emission sources and conducted a 1-y case study on the isotopic composition of atmospheric HONO at rural and urban sites. Interestingly, we identified that livestock farming is a previously overlooked direct source of HONO and determined its HONO to ammonia (NH3) emission ratio. Additionally, our results revealed that spatial and temporal variations in atmospheric HONO isotopic composition can be partially attributed to direct emissions. Through a detailed HONO budget analysis incorporating agricultural sources, we found that direct HONO emissions accounted for 39~45% of HONO production in rural areas across different seasons. The findings were further confirmed by chemistry transport model simulations, highlighting the significance of direct HONO emissions and their impact on air quality in the North China Plain. These findings provide compelling evidence that direct HONO emissions play a more substantial role in contributing to atmospheric HONO than previously believed. Moreover, the δ15N and δ18O isotopic fingerprints developed in this study may serve as a valuable tool for further research on the atmospheric chemistry of reactive nitrogen gases.

Imaging of pH distribution inside individual microdroplet by stimulated Raman microscopy.

Aerosol microdroplets as microreactors for many important atmospheric reactions are ubiquitous in the atmosphere. pH largely regulates the chemical processes within them; however, how pH and chemical species spatially distribute within an atmospheric microdroplet is still under intense debate. The challenge is to measure pH distribution within a tiny volume without affecting the chemical species distribution. We demonstrate a method based on stimulated Raman scattering microscopy to visualize the three-dimensional pH distribution inside single microdroplets of varying sizes. We find that the surface of all microdroplets is more acidic, and a monotonic trend of pH decreasing is observed in the 2.9-µm aerosol microdroplet from center to edge, which is well supported by molecular dynamics simulation. However, bigger cloud microdroplet differs from small aerosol for pH distribution. This size-dependent pH distribution in microdroplets can be related to the surface-to-volume ratio. This work presents noncontact measurement and chemical imaging of pH distribution in microdroplets, filling the gap in our understanding of spatial pH in atmospheric aerosol.

Quantification and Mechanistic Investigation of the Spontaneous H2O2 Generation at the Interfaces of Salt-Containing Aqueous Droplets.

There is now much evidence that OH radicals and H2O2 are spontaneously generated at the air-water interface of atmospheric aerosols. Here, we investigated the effect of halide anions (Cl-, Br-, I-), which are abundant in marine aerosols, on this H2O2 production. Droplets were generated via nebulization of water solutions containing Na2SO4, NaCl, NaBr, and NaI containing solutions, and H2O2 was monitored as a function of the salt concentration under atmospheric relevant conditions. The interfacial OH radical formation was also investigated by adding terephthalic acid (TA) to our salt solutions, and the product of its reaction with OH, hydroxy terephthalic acid (TAOH), was monitored. Finally, a mechanistic investigation was performed to examine the reactions participating in H2O2 production, and their respective contributions were quantified. Our results showed that only Br- contributes to the interfacial H2O2 formation, promoting the production by acting as an electron donor, while Na2SO4 and NaCl stabilized the droplets by only reducing their evaporation. TAOH was observed in the collected droplets and, for the first time, directly in the particle phase by means of online fluorescence spectroscopy, confirming the interfacial OH production. A mechanistic study suggests that H2O2 is formed by both OH and HO2 self-recombination, as well as HO2 reaction with H atoms. This work is expected to enhance our understanding of interfacial processes and assess their impact on climate, air quality, and health.

Phase State Regulates Photochemical HONO Production from NaNO3/Dicarboxylic Acid Mixtures.

Field observations of daytime HONO source strengths have not been well explained by laboratory measurements and model predictions up until now. More efforts are urgently needed to fill the knowledge gaps concerning how environmental factors, especially relative humidity (RH), affect particulate nitrate photolysis. In this work, two critical attributes for atmospheric particles, i.e., phase state and bulk-phase acidity, both influenced by ambient RH, were focused to illuminate the key regulators for reactive nitrogen production from typical internally mixed systems, i.e., NaNO3 and dicarboxylic acid (DCA) mixtures. The dissolution of only few oxalic acid (OA) crystals resulted in a remarkable 50-fold increase in HONO production compared to pure nitrate photolysis at 85% RH. Furthermore, the HONO production rates (PHONO) increased by about 1 order of magnitude as RH rose from <5% to 95%, initially exhibiting an almost linear dependence on the amount of surface absorbed water and subsequently showing a substantial increase in PHONO once nitrate deliquescence occurred at approximately 75% RH. NaNO3/malonic acid (MA) and NaNO3/succinic acid (SA) mixtures exhibited similar phase state effects on the photochemical HONO production. These results offer a new perspective on how aerosol physicochemical properties influence particulate nitrate photolysis in the atmosphere.

Unveiling the Molecular Characteristics, Origins, and Formation Mechanism of Reduced Nitrogen Organic Compounds in the Urban Atmosphere of Shanghai Using a Versatile Aerosol Concentration Enrichment System.

Reduced nitrogen-containing organic compounds (NOCs) in aerosols play a crucial role in altering their light-absorption properties, thereby impacting regional haze and climate. Due to the low concentration levels of individual NOCs in the air, the utilization of accurate detection and quantification technologies becomes essential. For the first time, this study investigated the diurnal variation, chemical characteristics, and potential formation pathways of NOCs in urban ambient aerosols in Shanghai using a versatile aerosol concentration enrichment system (VACES) coupled with HPLC-Q-TOF-MS. The results showed that NOCs accounted over 60% of identified components of urban organic aerosols, with O/N < 3 compounds being the major contributors (>70%). The predominance of the positive ionization mode suggested the prevalence of reduced NOCs. Higher relative intensities and number fractions of NOCs were observed during nighttime, while CHO compounds showed an opposite trend. Notably, a positive correlation between the intensity of NOCs and ammonium during the nighttime was observed, suggesting that the reaction of ammonium to form imines may be a potential pathway for the formation of reduced NOCs during the nighttime. Seven prevalent types of reduced NOCs in autumn and winter were identified and characterized by an enrichment of CH2 long-chain homologues. These NOCs included alkyl, cyclic, and aromatic amides in CHON compounds, as well as heterocyclic or cyclic amines and aniline homologue series in CHN compounds, which were associated with anthropogenic activities and may be capable of forming light-absorbing chromophores or posing harm to human health. The findings highlight the significant contributions of both primary emissions and ammonium chemistry, particularly amination processes, to the pollution of reduced NOCs in Shanghai's atmosphere.

Spontaneous Iodide Activation at the Air-Water Interface of Aqueous Droplets.

We present experimental evidence that atomic and molecular iodine, I and I2, are produced spontaneously in the dark at the air-water interface of iodide-containing droplets without any added catalysts, oxidants, or irradiation. Specifically, we observe I3- formation within droplets, and I2 emission into the gas phase from NaI-containing droplets over a range of droplet sizes. The formation of both products is enhanced in the presence of electron scavengers, either in the gas phase or in solution, and it clearly follows a Langmuir-Hinshelwood mechanism, suggesting an interfacial process. These observations are consistent with iodide oxidation at the interface, possibly initiated by the strong intrinsic electric field present there, followed by well-known solution-phase reactions of the iodine atom. This interfacial chemistry could be important in many contexts, including atmospheric aerosols.

Sunlight Induces the Production of Atmospheric Volatile Organic Compounds (VOCs) from Thermokarst Ponds.

Ground subsidence caused by permafrost thawing causes the formation of thermokarst ponds, where organic compounds from eroding permafrost accumulate. We photolyzed water samples from two such ponds in Northern Quebec and discovered the emission of volatile organic compounds (VOCs) using mass spectrometry. One pond near peat-covered permafrost mounds was organic-rich, while the other near sandy mounds was organic-poor. Compounds up to C10 were detected, comprising the atoms of O, N, and S. The main compounds were methanol, acetaldehyde, and acetone. Hourly VOC fluxes under actinic fluxes similar to local solar fluxes might reach up to 1.7 nmol C m-2 s-1. Unexpectedly, the fluxes of VOCs from the organic-poor pond were greater than those from the organic-rich pond. We suggest that different segregations of organics at the air/water interface may partly explain this observation. This study indicates that sunlit thermokarst ponds are a significant source of atmospheric VOCs, which may affect the environment and climate via ozone and aerosol formation. Further work is required for understanding the relationship between the pond's organic composition and VOC emission fluxes.

Chronic Exposure to Secondary Organic Aerosols Causes Lung Tissue Damage.

Recently, secondary organic aerosols (SOAs) emerged as a predominant component of fine particulate matter. However, the pathogenic mechanism(s) of SOAs are still poorly understood. Herein, we show that chronic exposure of mice to SOAs resulted in lung inflammation and tissue destruction. Histological analyses found lung airspace enlargement associated with massive inflammatory cell recruitment predominated by macrophages. Concomitant with such cell influx, our results found changes in the levels of a series of inflammatory mediators in response to SOA. Interestingly, we observed that the expression of the genes encoding for TNF-α and IL-6 increased significantly after one month of exposure to SOAs; mediators that have been largely documented to play a role in chronic pulmonary inflammatory pathologies. Cell culture studies confirmed these in vivo findings. Of importance as well, our study indicates increased matrix metalloproteinase proteolytic activity suggesting its contribution to lung tissue inflammation and degradation. Our work represents the first in vivo study, which reports that chronic exposure to SOAs leads to lung inflammation and tissue injury. Thus, we hope that these data will foster new studies to enhance our understanding of the underlying pathogenic mechanisms of SOAs and perhaps help in the design of therapeutic strategies against SOA-mediated lung injury.

Apportioning Atmospheric Ammonia Sources across Spatial and Seasonal Scales by Their Isotopic Fingerprint.

Mitigating ammonia (NH3) emissions is a significant challenge, given its well-recognized role in the troposphere, contributing to secondary particle formation and impacting acid rain. The difficulty arises from the highly uncertain attribution of atmospheric NH3 to specific emission sources, especially when accounting for diverse environments and varying spatial and temporal scales. In this study, we established a refined δ15N fingerprint for eight emission sources, including three previously overlooked sources of potential importance. We applied this approach in a year-long case study conducted in urban and rural sites located only 40 km apart in the Shandong Peninsula, North China Plain. Our findings highlight that although atmospheric NH3 concentrations and seasonal trends exhibited similarities, their isotopic compositions revealed significant distinctions in the primary NH3 sources. In rural areas, although agriculture emerged as the dominant emission source (64.2 ± 19.5%), a previously underestimated household stove source also played a considerably greater role, particularly during cold seasons (36.5 ± 12.5%). In urban areas, industry and traffic (33.5 ± 15.6%) and, surprisingly, sewage treatment (27.7 ± 11.3%) associated with high population density were identified as the major contributors. Given the relatively short lifetime of atmospheric NH3, our findings highlight the significance of the isotope approach in offering a more comprehensive understanding of localized and seasonal influences of NH3 sources compared to emissions inventories. The refined isotopic fingerprint proves to be an effective tool in distinguishing source contributions across spatial and seasonal scales, thereby providing valuable insights for the development of emission mitigation policies aimed at addressing the increasing NH3 burden on the local atmosphere.

Pathogenic Mechanisms of Secondary Organic Aerosols.

Air pollution represents a major health problem and an economic burden. In recent years, advances in air pollution research has allowed particle fractionation and identification of secondary organic aerosol (SOA). SOA is formed from either biogenic or anthropogenic emissions, through a mass transfer from the gaseous mass to the particulate phase in the atmosphere. They can have deleterious impact on health and the mortality of individuals with chronic inflammatory diseases. The pleiotropic effects of SOA could involve different and interconnected pathogenic mechanisms ranging from oxidative stress, inflammation, and immune system dysfunction. The purpose of this review is to present recent findings about SOA pathogenic roles and potential underlying mechanisms focusing on the lungs; the latter being the primary exposed organ to atmospheric pollutants.

Nitrogen-Containing Compounds Enhance Light Absorption of Aromatic-Derived Brown Carbon.

The formation of secondary brown carbon (BrC) is chemically complex, leading to an unclear relationship between its molecular composition and optical properties. Here, we present an in-depth investigation of molecular-specific optical properties and aging of secondary BrC produced from the photooxidation of ethylbenzene at varied NOx levels for the first time. Due to the pronounced formation of unsaturated products, the mass absorption coefficient (MAC) of ethylbenzene secondary organic aerosols (ESOA) at 365 nm was higher than that of biogenic SOA by a factor of 10. A high NOx level ([ethylbenzene]0/[NOx]0 < 10 ppbC ppb-1) was found to significantly increase the average MAC300-700nm of ESOA by 0.29 m2 g-1. The data from two complementary high-resolution mass spectrometers and quantum chemical calculations suggested that nitrogen-containing compounds were largely responsible for the enhanced light absorption of high-NOx ESOA, and multifunctional nitroaromatic compounds (such as C8H9NO3 and C8H9NO4) were identified as important BrC chromophores. High-NOx ESOA underwent photobleaching upon direct exposure to ultraviolet light. Photolysis did not lead to the significant decomposition of C8H9NO3 and C8H9NO4, indicating that nitroaromatic compounds may serve as relatively stable nitrogen reservoirs and would effectively absorb solar radiation during the daytime.

Field Detection of Highly Oxygenated Organic Molecules in Shanghai by Chemical Ionization-Orbitrap.

Secondary organic aerosol, formed through atmospheric oxidation processes, plays an important role in affecting climate and human health. In this study, we conducted a comprehensive campaign in the megacity of Shanghai during the 2019 International Import Expo (EXPO), with the first deployment of a chemical ionization─Orbitrap mass spectrometer for ambient measurements. With the ultrahigh mass resolving power of the Orbitrap mass analyzer (up to 140,000 Th/Th) and capability in dealing with massive spectral data sets by positive matrix factorization, we were able to identify the major gas-phase oxidation processes leading to the formation of oxygenated organic molecules (OOM) in Shanghai. Nine main factors from three independent sub-range analysis were identified. More than 90% of OOM are of anthropogenic origin and >60% are nitrogen-containing molecules, mainly dominated by the RO2 + NO and/or NO3 chemistry. The emission control during the EXPO showed that even though the restriction was effectual in significantly lowering the primary pollutants (20-70% decrease), the secondary oxidation products responded less effectively (14% decrease), or even increased (50 to >200%) due to the enhancement of ozone and the lowered condensation sink, indicating the importance of a stricter multi-pollutant coordinated strategy in primary and secondary pollution mitigation.

Seasonal variation of water-soluble brown carbon in Qingdao, China: Impacts from marine and terrestrial emissions.

Brown carbon (BrC) has been attracting more and more attention owing to its significant effects on climate. However, the limited knowledge on its chemical composition and sources limits the precision of aerosol radiative forcing estimated by climate models. In this study, the chemical components of PM2.5 and optical properties of water-soluble BrC (WS-BrC) were investigated from atmospheric particles collected in summer and winter in Qingdao, China. On the whole, though there were slight diurnal variations, seasonal differences were more obvious. Due to the influence of emission sources and meteorological conditions, the heavier pollution of carbonaceous aerosols occurred in winter. By comparison, the absorption Ångström exponent (AAE) and mass absorption efficiency of WS-BrC at 365 nm (MAE365) showed that WS-BrC in winter had stronger wavelength dependence and light absorption capacity, which might be associated with biomass burning source contributions. This was further confirmed by a strong correlation between the light absorption coefficient at 365 nm (Abs365) and non-sea salt K+, an indicator for biomass burning emissions. Four fluorescent components (C1∼C4) with high unsaturation in water-soluble organic carbon (WSOC) were identified by excitation-emission matrix fluorescence spectroscopy combined with parallel factor analysis method, which showed that WSOC in Qingdao was mainly related to humic-like chromophores. It is worth noting that C1 was similar to the water-soluble chromophore of simulated marine aerosols, which proved that marine emissions do have a certain impact on atmospheric particulate matter in coastal areas. In addition, the results of source analysis showed that WS-BrC originated from different terrestrial sources in different seasons. The current results may help to improve the knowledge of optical properties of WS-BrC in coastal cities, optimize the global climate model and formulate air management policies.

Indoor heterogeneous photochemistry of molds and their contribution to HONO formation.

To better understand the impact of molds on indoor air quality, we studied the photochemistry of microbial films made by Aspergillus niger species, a common indoor mold. Specifically, we investigated their implication in the conversion of adsorbed nitrate anions into gaseous nitrous acid (HONO) and nitrogen oxides (NOx ), as well as the related VOC emissions under different indoor conditions, using a high-resolution proton transfer reaction-time of flight-mass spectrometer (PTR-TOF-MS) and a long path absorption photometer (LOPAP). The different mold preparations were characterized by the means of direct injection into an Orbitrap high-resolution mass spectrometer with a heated electrospray ionization (ESI-Orbitrap-MS). The formation of a wide range of VOCs, having emission profiles sensitive to the types of films (either doped by potassium nitrate or not), cultivation time, UV-light irradiation, potassium nitrate concentration and relative humidity was observed. The formation of nitrous acid from these films was also determined and found to be dependent on light and relative humidity. Finally, the reaction paths for the NOx and HONO production are proposed. This work helps to better understand the implication of microbial surfaces as a new indoor source for HONO emission.

Machine-learning Models Predict 30-Day Mortality, Cardiovascular Complications, and Respiratory Complications After Aseptic Revision Total Joint Arthroplasty.

BACKGROUND: Aseptic revision THA and TKA are associated with an increased risk of adverse outcomes compared with primary THA and TKA. Understanding the risk profiles for patients undergoing aseptic revision THA or TKA may provide an opportunity to decrease the risk of postsurgical complications. There are risk stratification tools for postoperative complications after aseptic revision TKA or THA; however, current tools only include nonmodifiable risk factors, such as medical comorbidities, and do not include modifiable risk factors. QUESTIONS/PURPOSES: (1) Can machine learning predict 30-day mortality and complications for patients undergoing aseptic revision THA or TKA using a cohort from the American College of Surgeons National Surgical Quality Improvement Program database? (2) Which patient variables are the most relevant in predicting complications? METHODS: This was a temporally validated, retrospective study analyzing the 2014 to 2019 National Surgical Quality Improvement Program database, as this database captures a large cohort of aseptic revision THA and TKA patients across a broad range of clinical settings and includes preoperative laboratory values. The training data set was 2014 to 2018, and 2019 was the validation data set. Given that predictive models learn expected prevalence of outcomes, this split allows assessment of model performance in contemporary patients. Between 2014 and 2019, a total of 24,682 patients underwent aseptic revision TKA and 17,871 patients underwent aseptic revision THA. Of those, patients with CPT codes corresponding to aseptic revision TKA or THA were considered as potentially eligible. Based on excluding procedures involving unclean wounds, 78% (19,345 of 24,682) of aseptic revision TKA procedures and 82% (14,711 of 17,871) of aseptic revision THA procedures were eligible. Ten percent of patients in each of the training and validation cohorts had missing predictor variables. Most of these missing data were preoperative sodium or hematocrit (8% in both the training and validation cohorts). No patients had missing outcome data. No patients were excluded due to missing data. The mean patient was age 66 ± 12 years, the mean BMI was 32 ± 7 kg/m 2 , and the mean American Society of Anesthesiologists (ASA) Physical Score was 3 (56%). XGBoost was then used to create a scoring tool for 30-day adverse outcomes. XGBoost was chosen because it can handle missing data, it is nonlinear, it can assess nuanced relationships between variables, it incorporates techniques to reduce model complexity, and it has a demonstrated record of producing highly accurate machine-learning models. Performance metrics included discrimination and calibration. Discrimination was assessed by c-statistics, which describe the area under the receiver operating characteristic curve. This quantifies how well a predictive model discriminates between patients who have the outcome of interest versus those who do not. Relevant ranges for c-statistics include good (0.70 to 0.79), excellent (0.80 to 0.89), and outstanding (> 0.90). We estimated 95% confidence intervals (CIs) for c-statistics by 500-sample bootstrapping. Calibration curves quantify reliability of model predictions. Reliable models produce prediction probabilities for outcomes that are similar to observed probabilities of those outcomes, so a well-calibrated model should demonstrate a calibration curve that does not deviate substantially from a line of slope 1 and intercept 0. Calibration curves were generated on the 2019 validation data. Shapley Additive Explanations (SHAP) visualizations were used to investigate feature importance to gain insight into how models made predictions. The models were built into an online calculator for ongoing testing and validation. The risk calculator, which is freely available ( http://nb-group.org/rev2/ ), allows a user to input patient data to calculate postoperative risk of 30-day mortality, cardiac, and respiratory complications after aseptic revision TKA or THA. A post hoc analysis was performed to assess whether using data from 2020 would improve calibration on 2019 data. RESULTS: The model accurately predicted mortality, cardiac complications, and respiratory complications after aseptic revision THA or TKA, with c-statistics of 0.88 (95% CI 0.83 to 0.93), 0.80 (95% CI 0.75 to 0.84), and 0.78 (95% CI 0.74 to 0.82), respectively, on internal validation and 0.87 (95% CI 0.77 to 0.96), 0.70 (95% CI 0.61 to 0.78), and 0.82 (95% CI 0.75 to 0.88), respectively, on temporal validation. Calibration curves demonstrated slight over-confidence in predictions (most predicted probabilities were higher than observed probabilities). Post hoc analysis of 2020 data did not yield improved calibration on the 2019 validation set. Important risk factors for all models included increased age and higher ASA, BMI, hematocrit level, and sodium level. Hematocrit and ASA were in the top three most important features for all models. The factor with the strongest association for mortality and cardiac complication models was age, and for the respiratory model, chronic obstructive pulmonary disease. Risk related to sodium followed a U-shaped curve. Preoperative hyponatremia and hypernatremia predicted an increased risk of mortality and respiratory complications, with a nadir of 138 mmol/L; hyponatremia was more strongly associated with mortality than hypernatremia. A hematocrit level less than 36% predicted an increased risk of all three adverse outcomes. A BMI less than 24 kg/m 2 -and especially less than 20 kg/m 2 -predicted an increased risk of all three adverse outcomes, with little to no effect for higher BMI. CONCLUSION: This temporally validated model predicted 30-day mortality, cardiac complications, and respiratory complications after aseptic revision THA or TKA with c-statistics ranging from 0.78 to 0.88. This freely available risk calculator can be used preoperatively by surgeons to educate patients on their individual postoperative risk of these specific adverse outcomes. Unanswered questions that remain include whether altering the studied preoperative patient variables, such as sodium or hematocrit, would affect postoperative risk of adverse outcomes; however, a prospective cohort study is needed to answer this question. LEVEL OF EVIDENCE: Level III, therapeutic study.

Symptom Burden and Palliative Care Needs of Patients with Incurable Cancer at Diagnosis and During the Disease Course.

BACKGROUND: Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied. MATERIAL AND METHODS: We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self-report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL-Q], Patients Health Questionnaire-4 [PHQ-4], modified Supportive Care Needs Survey [SCNS-SF-34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow-up. RESULTS: From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%). CONCLUSION: Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care. IMPLICATIONS FOR PRACTICE: A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients' needs.

Anthropogenic-Biogenic Interactions at Night: Enhanced Formation of Secondary Aerosols and Particulate Nitrogen- and Sulfur-Containing Organics from ß-Pinene Oxidation.

Mixing of anthropogenic gaseous pollutants and biogenic volatile organic compounds impacts the formation of secondary aerosols, but still in an unclear manner. The present study explores secondary aerosol formation via the interactions between ß-pinene, O3, NO2, SO2, and NH3 under dark conditions. Results showed that aerosol yield can be largely enhanced by more than 330% by NO2 or SO2 but slightly enhanced by NH3 by 39% when the ratio of inorganic gases to ß-pinene ranged from 0 to 1.3. Joint effects of NO2 and SO2 and SO2 and NH3 existed as aerosol yields increased with NO2 but decreased with NH3 when SO2 was kept constant. Infrared spectra showed nitrogen-containing aerosol components derived from NO2 and NH3 and sulfur-containing species derived from SO2. Several particulate organic nitrates (MW 215, 229, 231, 245), organosulfates (MW 250, 264, 280, 282, 284), and nitrooxy organosulfates (MW 295, 311, 325, 327, and 343) were identified using high-resolution orbitrap mass spectrometry in NO2 and SO2 experiments, and their formation mechanism is discussed. Most of these nitrogen- and sulfur-containing species have been reported in ambient particles. Our results suggest that the complex interactions among ß-pinene, O3, NO2, SO2, and NH3 during the night might serve as a potential pathway for the formation of particulate nitrogen- and sulfur-containing organics, especially in polluted regions with both anthropogenic and biogenic influences.

Elucidating an Atmospheric Brown Carbon Species-Toward Supplanting Chemical Intuition with Exhaustive Enumeration and Machine Learning.

Brown carbon (BrC) is involved in atmospheric light absorption and climate forcing and can cause adverse health effects. Understanding the formation mechanisms and molecular structure of BrC is of key importance in developing strategies to control its environment and health impact. Structure determination of BrC is challenging, due to the lack of experiments providing molecular fingerprints and the sheer number of molecular candidates with identical mass. Suggestions based on chemical intuition are prone to errors due to the inherent bias. We present an unbiased algorithm, using graph-based molecule generation and machine learning, which can identify all molecular structures of compounds involved in biomass burning and the composition of BrC. We apply this algorithm to C12H12O7, a light-absorbing "test case" molecule identified in chamber experiments on the aqueous photo-oxidation of syringol, a prevalent marker in wood smoke. Of the 260 million molecular graphs, the algorithm leaves only 36,518 (0.01%) as viable candidates matching the spectrum. Although no unique molecular structure is obtained from only a chemical formula and a UV/vis absorption spectrum, we discuss further reduction strategies and their efficacy. With additional data, the method can potentially more rapidly identify isomers extracted from lab and field aerosol particles without introducing human bias.