Environmental influences on Arctic halogen chemistry: investigation of melt onset and snowpack properties

Thesis (M.S.) University of Alaska Fairbanks, 2016Reactive halogen radicals (e.g. Br, Cl and their oxide forms) dominate tropospheric oxidation mechanisms during Arctic springtime (Feb. – Apr.) by depleting ozone and changing the fate of pollutants. During ozone depletion events, reactive bromine radicals rapidly oxidize mercury which gets subsequently deposited, becoming more bioavailable. During Arctic springtime, a heterogeneous surface reaction (referred to as BrO recycling) between hypobromous acid (HOBr) and bromide (Br-) rapidly increases the abundance of reactive bromine episodically up to 40 pptv peaks. However, as spring transitions to summer (May - June), elevated reactive bromine levels suddenly decrease. There are two key requirements to maintain BrO recycling including surface area and sea salt (i.e. bromide) abundance. This study investigated environmental factors that impact BrO recycling during late spring (May-June) in the Arctic, including temperature, snowpack depth and rain/snow precipitation events. Near horizon BrO was measured using Multi-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) at Barrow, AK and above frozen Arctic sea ice. The late spring “end” to elevated reactive bromine (referred as the Seasonal End Date, SED) was objectively determined at all sites (N=12). Air temperature derived melt onset dates were determined for all sites (N=12) and occurred within two days of the SED (RMS = 1.8 days, R² = 0.989). Through these studies, we determined BrO recycling is hindered by melt onset of snowpack, ending the reactive bromine season.Chapter 1: Introduction -- 1.1 Motivation -- 1.2 Arctic tropospheric chemistry -- 1.3 Bromine explosion mechanism -- 1.3.1 Saline surfaces -- 1.3.2 Snow surface area -- 1.4 Melt onset -- 1.5 Ion pulse -- 1.6 Gas-phase bromine seasonal behavior -- 1.7 Multi-AXis differential optical absorption spectroscopy (MAX-DOAS) -- 1.8 Thesis structure -- 1.9 References -- 1.10 Figures -- Chapter 2: Late spring snow melt onset hinders bromine monoxide heterogeneous recycling in the arctic -- 2.1 Introduction -- 2.2 Data sources and methods -- 2.2.1 Bromine monoxide measurement sites -- 2.2.2 Snow/ rain precipitation observations and snow depth measurements -- 2.2.3 Objective determination of seasonal end and recurrence events -- 2.2.4 Objective determination of melt onset dates using surface air temperature -- Results -- 2.3.1 Seasonal end date determination and sensitivity to threshold parameters -- 2.3.2 Melt onset determination and correlation to the seasonal end date -- 2.3.3 Snow depth changes at seasonal end and recurrence events -- 2.3.4 Rain/snow precipitation at seasonal end and recurrence events -- 2.4 Discussion -- 2.4.1 Seasonal end date is the melt onset date -- 2.4.2 Decaying snowpack and rain precipitation prevents BrO recycling -- 2.4.3 Below freezing temperatures and new surface area re-initialize BrO recycling -- 2.5 Conclusion -- 2.6 Acknowledgements -- 2.7 References -- 2.8 Figures -- Chapter 3: Conclusions and outlook -- 3.1 Conclusions -- 3.2 Future Outlook -- 3.3 References

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Length of Stay per Total Body Surface Area Burn Relative to Mechanism: A Pediatric Injury Quality Improvement Collaborative Study

Studies on length of stay (LOS) per total body surface area (TBSA) burn in pediatric patients are often limited to single institutions and are grouped in ranges of TBSA burn which lacks specific detail to counsel patients and families. A LOS to TBSA burn ratio of 1 has been widely accepted but not validated with multi-institution data. The objective of this study is to describe the current relationship of LOS per TBSA burn and LOS per TBSA burn relative to burn mechanism with the use of multi-institutional data. Data from the Pediatric Injury Quality Improvement Collaborative (PIQIC) were obtained for patients across five pediatric burn centers from July 2018 to September 2020. LOS per TBSA burn ratios were calculated. Descriptive statistics and generalized linear regression which modeled characteristics associated with LOS per TBSA ratio are described. Among the 1267 pediatric burn patients, the most common mechanism was scald (64%), followed by contact (17%) and flame (13%). The average LOS/TBSA burn ratio across all cases was 1.2 (SD = 2.1). In adjusted models, scald burns and chemical burns had similar LOS/TBSA burn ratios of 0.8 and 0.9, respectively, whereas all other burns had a significantly higher LOS/TBSA burn ratio (p<0.0001). LOS/TBSA burn ratios were similar across races, although Hispanics had a slightly higher ratio at 1.4 days. These data establish a multi-institution LOS per TBSA ratio across PIQIC centers and demonstrate a significant variation in the LOS per TBSA burn relative to the burn mechanism sustained

Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1). Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges

Timing and volume of crystalloid and blood products in pediatric trauma: An Eastern Association for the Surgery of Trauma multicenter prospective observational study

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. BACKGROUND The purpose of this study was to determine the relationship between timing and volume of crystalloid before blood products and mortality, hypothesizing that earlier transfusion and decreased crystalloid before transfusion would be associated with improved outcomes. METHODS A multi-institutional prospective observational study of pediatric trauma patients younger than 18 years, transported from the scene of injury with elevated age-adjusted shock index on arrival, was performed from April 2018 to September 2019. Volume and timing of prehospital, emergency department, and initial admission resuscitation were assessed including calculation of 20 ± 10 mL/kg crystalloid boluses overall and before transfusion. Multivariable Cox proportional hazards and logistic regression models identified factors associated with mortality and extended intensive care, ventilator, and hospital days. RESULTS In 712 children at 24 trauma centers, mean age was 7.6 years, median (interquartile range) Injury Severity Score was 9 (2-20), and in-hospital mortality was 5.3% (n = 38). There were 311 patients(43.7%) who received at least one crystalloid bolus and 149 (20.9%) who received blood including 65 (9.6%) with massive transfusion activation. Half (53.3%) of patients who received greater than one crystalloid bolus required transfusion. Patients who received blood first (n = 41) had shorter median time to transfusion (19.8 vs. 78.0 minutes, p = 0.005) and less total fluid volume (50.4 vs. 86.6 mL/kg, p = 0.033) than those who received crystalloid first despite similar Injury Severity Score (median, 22 vs. 27, p = 0.40). On multivariable analysis, there was no association with mortality (p = 0.51); however, each crystalloid bolus after the first was incrementally associated with increased odds of extended ventilator, intensive care unit, and hospital days (all p \u3c 0.05). Longer time to transfusion was associated with extended ventilator duration (odds ratio, 1.11; p = 0.04). CONCLUSION Resuscitation with greater than one crystalloid bolus was associated with increased need for transfusion and worse outcomes including extended duration of mechanical ventilation and hospitalization in this prospective study. These data support a crystalloid-sparing, early transfusion approach for resuscitation of injured children. LEVEL OF EVIDENCE Therapeutic, level IV