PHYSICAL, OPTICAL, AND CHEMICAL PROPERTIES OF LIGHT ABSORBING AEROSOLS AND THEIR CLIMATIC IMPACTS

Aerosols are particles suspended in the atmosphere; they are emitted during natural phenomena such as dust storms, wildfires, and volcanic eruptions, and during anthropogenic activities like household wood burning, vehicles operations, and industrial productions, or they can form in the atmosphere from gas to particle partition. Aerosols impact earth’s weather and climate by absorbing and scattering the incoming solar and the outgoing earth thermal radiation and interacting with clouds. The optical properties of aerosols evolve as the chemical and physical properties vary during their residence in the atmosphere. In addition, the aerosols’ properties strongly depend on the vertical distribution in the atmosphere. Due to the dynamic and heterogenous nature of the aerosol properties, their optical characteristics are still highly uncertain and hence, it is essential to quantify their ability to absorb and scatter light. To address this knowledge gap, we studied atmospheric particles in three different regions of the world with different environmental conditions and particle compositions. To investigate the details of aerosols as a function of height, we studied how their optical properties vary vertically using a tethered balloon system at the U.S. Department of Energy Atmospheric Radiation Measurement Southern Great Plains site in Oklahoma. We also estimated the top of the atmosphere radiative forcing using Lorentz-Mie simulations and the Santa Barbara Disort Atmospheric Radiative Transfer (SBDART) model. In a second study, we collected aerosol samples at a mountaintop site in Italy to study aerosols transported over long ranges. In the samples, we found an abundance of tar balls which are a kind of particles often detected in biomass-burning plumes (e.g., wildfire smoke). Tar balls absorb light at shorter wavelengths falling within the particle category often referred to as brown carbon; however, the reported complex refractive indices in the literature are highly variable. Therefore, we estimated the refractive index (RI) and optical properties of single tar balls using electron energy loss spectroscopy. We also estimated their radiative forcing to understand their potential impacts on climate and weather systems. In a third study on aerosol processing in haze conditions, we used microscopy and mass spectrometry techniques to observe the abundance of organosulfates formed through multiphase chemical reactions between organic and sulfate particles collected in the Indo-Gangetic region. The formation of organosulfates was recently shown to increase the light absorption by organic particles in the ultraviolet and visible spectral range. Finally, we classified aerosols based on their chemical composition and phase state which also affect the aerosol optical properties in complex manners. My thesis discusses the chemical, physical, and optical properties of atmospheric aerosols providing data that can be used in climate and weather models to reduce uncertainties and enhance their predictability skills

Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective medical therapies. Recent research has focused on identifying the biological processes essential to the development and progression of fibrosis, and on the mediators driving these processes. Lysophosphatidic acid (LPA), a biologically active lysophospholipid, is one such mediator. LPA has been found to be elevated in bronchoalveolar lavage (BAL) fluid of IPF patients, and through interaction with its cell surface receptors, it has been shown to drive multiple biological processes implicated in the development of IPF. Accordingly, the first clinical trial of an LPA receptor antagonist in IPF has recently been initiated. In addition to being a therapeutic target, LPA also has potential to be a biomarker for IPF. There is increasing interest in exhaled breath condensate (EBC) analysis as a non-invasive method for biomarker detection in lung diseases, but to what extent LPA is present in EBC is not known. Methods: In this study, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess for the presence of LPA in the EBC and plasma from 11 IPF subjects and 11 controls. Results: A total of 9 different LPA species were detectable in EBC. Of these, docosatetraenoyl (22:4) LPA was significantly elevated in the EBC of IPF subjects when compared to controls (9.18 pM vs. 0.34 pM; p = 0.001). A total of 13 different LPA species were detectable in the plasma, but in contrast to the EBC, there were no statistically significant differences in plasma LPA species between IPF subjects and controls. Conclusions: These results demonstrate that multiple LPA species are detectable in EBC, and that 22:4 LPA levels are elevated in the EBC of IPF patients. Further research is needed to determine the significance of this elevation of 22:4 LPA in IPF EBC, as well as its potential to serve as a biomarker for disease severity and/or progression

Molecular and physical composition of tar balls in wildfire smoke: an investigation with complementary ionisation methods and 15-Tesla FT-ICR mass spectrometry

Tar balls (TBs) are a major carbonaceous product of wildfires and other biomass-burning events that often exceed soot or other elemental forms of carbon in number and mass. Being a recalcitrant fraction of organic carbon, TBs are capable of long-range atmospheric transport, and thus, exert influence not only in the vicinity of wildfires but also in remote regions. Here, we characterised ambient atmospheric aerosol samples with varying TB number fractions collected downwind of Pacific Northwest wildfires using a 15-Tesla Fourier transform-ion cyclotron resonance mass spectrometer (15-T FT-ICR MS). Relative to non-TB aerosol, we found 2006 and 851 molecular formulae exclusively in TB-rich aerosol using laser desorption ionisation (LDI) of samples directly from an aerosol-loaded substrate and electrospray ionisation (ESI) of ACN-extracted aerosol, respectively. Elemental composition from LDI/15-T FT-ICR MS revealed TBs to be abundant in molecular species of low volatility and high viscosity, providing molecular detail that was consistent with key climate and air quality-related properties of TBs. Our findings demonstrate that the TB-specific molecular composition obtained from (−)LDI/15-T FT-ICR MS not only complements (−)ESI analyses, but provides a more apt reflection of the physical properties of TBs as well. We provide proof-of-concept evidence for the potential value of using LDI/15-T FT-ICR MS in routine OA analyses, specifically smoke samples rich in refractory OA, and improve the representation of OA in atmospheric and climate modelling studies that aim to fully understand its impact and occurrence

Outcome and renal function following salvage surgery for bilateral Wilms tumor: a single-institution experience

Objective: The aim of this study was to determine the surgical outcomes and renal function following salvage surgery for bilateral Wilms tumor (BWT). Summary background data The challenge for the surgeon treating BWT lies in striking a fine balance between renal preservation and oncological clearance.Methods: This is a retrospective review of medical records in a tertiary care hospital in India. Nine children with BWT who presented between 2005 and 2015 were reviewed and followed up through telephone. Survival rates were calculated using the Kaplan–Meier method. A P value of less than 0.05 was considered statistically significant.Results: Seven (78%) of nine children were boys and two (22%) were syndromic. Six (67%) children presented at less than 1 year of age. Eight (89%) children presented with an abdominal mass. There were no metastases at presentation. All children underwent trucut biopsy and neoadjuvant chemotherapy. Six children underwent surgery: four underwent bilateral nephron sparing surgery (NSS) and two underwent unilateral nephrectomy with contralateral NSS. Tumor recurred in two children. The mean follow-up was 38 months (range: 5–108 months). Creatinine clearance (CrCl) improved postoperatively in all children. Postoperative hypertension was transient and resolved with improvement in CrCl.Conclusion: Children with BWT in the Indian subcontinent may be younger than those in the rest of the world. NSS yields good outcomes even for recurrences. Postoperative hypertension is transient in the majority of patients and correlated with improvement in CrCl. Prognosis is related to operability and syndromic association.Keywords: bilateral Wilms, creatinine clearance, hypertension, nephron sparing surger

The peace that I wanted, I got: Qualitative insights from patient experiences of SMART DAPPER interventions for major depression and traumatic stress disorders in Kenya.

SMART DAPPER is an implementation science study responding to mental health treatment gaps for depression and trauma-related disorders in Sub-Saharan Africa (SSA). We report on patient experiences in a study using a Sequential, Multiple Assignment Randomized Trial (SMART) design to test first and second line non-specialist treatment using psychotherapy (Interpersonal Psychotherapy [IPT] or medication (fluoxetine [FLX]), integrated within public sector primary care in western Kenya. An embedded qualitative study conducted in-depth interviews (n = 17) and three (n = 3) focus group discussions with participants (May to October 2021). Audio-recorded interviews were transcribed and translated into English; we deductively and inductively analyzed transcripts guided by grounded theoretical approaches and content analysis. We drew on the health belief model and socio-ecological framework to present findings, including perceived severity (motivations for taking part in the intervention), impacts of the intervention at the individual, interpersonal, and community and health systems levels as well as barriers and facilitators. Participants discussed family and marital conflict, loss of a child, loss of income or a job, and traumatic events such as a death or illness. Impacts at the individual level included reduced headaches, improved appetite and weight management, increased energy, improved sleep, better self-efficacy, and improved concentration, which was reported to lead to increased economic opportunities. At the interpersonal level, participants noted a reduction in conflict, better conflict management and resolution, increased harmony with family and community members, and improved relationships with their partners and children. Perceived challenges included balancing the intervention with livelihoods, preference for traditional medicines, actual or anticipated side effects with medication (FLX), mental health stigma, major life events, and perceived inadequate counseling and challenges with providers. The findings demonstrate the potential of the SMART DAPPER intervention for depression and trauma-related disorder treatments and underscore the challenges and barriers that must be addressed when scaling similar interventions. Trial registration: ClinicalTrials.gov identifier: NCT03466346

Serum Amyloid P Therapeutically Attenuates Murine Bleomycin-Induced Pulmonary Fibrosis via Its Effects on Macrophages

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcγ receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses

Treatment Outcomes for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study of the Impact of Immunosuppression on Pulmonary Function Trajectory

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. RESULTS: Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC % predicted was found after 12 months of treatment compared with the potential 12-month response without treatment (+3.90%; P ≤ .001; 95% CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted also improved at 12 months (+4.53%; P ≤ .001; 95% CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. INTERPRETATION: Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings

Pulmonary Hypertension and Anastrozole (PHANTOM): A Randomized, Double-Blind, Placebo-Controlled Trial

Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved six-minute walk distance (6MWD) at six months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled Phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four post-menopausal women and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at six months. Using intent-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued study drug. There was no significant difference in the change in 6MWD at six months (placebo-corrected treatment effect -7.9 m, 95%CI -32.7 – 16.9, p = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared to placebo in post-menopausal women and men with PAH. Anastrozole was safe and did not show adverse effects. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03229499

Predicted distribution of the yellow-throated marten Martes flavigula (Mammalia: Carnivora: Mustelidae) on Borneo

The yellow-throated marten Martes flavigula is a wide-ranging species across much of Asia. It is active mainly during the day, is semi-arboreal and has an omnivorous diet. On Borneo, it has a wide elevation range, from coastal lowland to lower montane habitat of 1700 m a.s.l. Records from camera-trapping and other wildlife surveys imply a widespread distribution, but the species is encountered less frequently than in many other parts of its global range. We collected a total of 195 occurrence records from all political units of Borneo except South Kalimantan. To reduce possibly confounding effects of sampling bias on habitat suitability we used 56 records in a Balanced Model and 94 records in a Spatial Filtering Model. Respondents’ opinions on habitat preference showed large variation, except for lowland and upland dipterocarp forests, which were consistently perceived as highly suitable; disturbed areas such as burnt forests and bare areas were perceived to be less favourable. The habitat suitability model predicted that the yellow-throated marten is widespread within Borneo, likely to occur in mosaics of lowland and upland forests, including old plantations and active logging areas; but unlikely to use young plantations and crops, perhaps including oil palm plantations. The effects of logging on yellow-throated marten are not well understood, yet the species’s population size on Borneo will depend on how tree plantations and logging concessions are managed and harvested. More surveys above about 1200 m a.s.l., where information is still limited, would enable more confident habitat assessments. Further research could determine if the Bornean subspecies, M. f. saba, could be a cryptic species