Watershed-Scale Drivers of Air-Water CO2 Exchanges in Two Lagoonal North Carolina (USA) Estuaries

Riverine loading of nutrients and organic matter act in concert to modulate CO2 fluxes in estuaries, yet quantitative relationships between these factors remain poorly defined. This study explored watershed-scale mechanisms responsible for the relatively low CO2 fluxes observed in two microtidal, lagoonal estuaries. Air-water CO2 fluxes were quantified with 74 high-resolution spatial surveys in the neighboring New River Estuary (NewRE) and Neuse River Estuary (NeuseRE), North Carolina, which experience a common climatology but differ in marine versus riverine influence. Annually, both estuaries were relatively small sources of CO2 to the atmosphere, 12.5 and 16.3mmolCm(-2)d(-1) in the NeuseRE and NewRE, respectively. Large-scale pCO(2) variations were driven by changes in freshwater age, which modulates nutrient and organic carbon supply and phytoplankton flushing. Greatest pCO(2) undersaturation was observed at intermediate freshwater ages, between 2 and 3weeks. Biological controls on CO2 fluxes were obscured by variable inputs of river-borne CO2, which drove CO2 degassing in the river-dominated NeuseRE. Internally produced CO2 exceeded river-borne CO2 in the marine-dominated NewRE, suggesting that net ecosystem heterotrophy, rather than riverine inputs, drove CO2 fluxes in this system. Variations in riverine alkalinity and inorganic carbon loading caused zones of minimum buffering capacity to occur at different locations in each estuary, enhancing the sensitivity of estuarine inorganic C chemistry to acidification. Although annual CO2 fluxes were similar between systems, watershed-specific hydrologic factors led to disparate controls on internal carbonate chemistry, which can influence ecosystem biogeochemical cycling, trophic state, and response to future perturbations. Plain Language Summary Estuaries release nearly as much CO2 to the atmosphere as is taken up over the continental shelf. However, estuarine emissions vary greatly across space and time, contributing significantly to the uncertainty of global carbon budgets. In this study, we assess spatial and temporal variability in CO2 emissions from adjacent estuaries in North Carolina, USA. These emissions varied across seasons and river discharge conditions but were relatively small when assessed as annual averages. Freshwater age (time freshwater spends in estuary before being flushed to ocean) was an important driver of CO2 dynamics in both estuaries, due to its role in regulating nutrient, DOC, and DIC supply while also affecting the rate at which phytoplankton are flushed from the system. While the relationship between freshwater age and CO2 was similar for both estuaries, we show that the various external and internal inputs of CO2 were quite different. Riverine CO2 inputs drove CO2 emissions in the river-dominated estuary, while internally produced CO2 (from community respiration) was more important in the marine-dominated estuary. We also demonstrate that poorly buffered regions in both estuaries are particularly vulnerable to acidification, with potentially negative impacts on calcifying organisms

Carbon budget of a shallow, lagoonal estuary: Transformations and source-sink dynamics along the river-estuary-ocean continuum

A comprehensive carbon budget was constructed to quantify carbon flows through the freshwater-marine continuum of a temperate, microtidal estuary. We performed coordinated measurements of dissolved inorganic carbon and total organic carbon fluxes to resolve spatial variability between and along the channel and shoals and diel variability across the entire estuary for 2 yr. Net ecosystem metabolism (NEM) was the most significant control on carbon flow within estuary regions. However, metabolic rates were spatially coupled such that counteracting fluxes across the channel-shoal gradient or along the river-ocean gradient resulted in system-wide NEM that was closely in balance (-3.0 +/- 3.3 to 1.1 +/- 4.4 molC m(-2) yr(-1)). Similarly, large diel and seasonal variability in air-water CO2 fluxes were observed during 72 spatial surveys, but these short-term variations generally cancelled out when aggregated to annual budget terms. Although atmospheric exchanges were small (-0.2 +/- 0.1 to 2.0 +/- 0.4 molC m(-2) yr(-1)), they were subject to large errors (+/- 4 molC m(-2) yr(-1)) if diel variability was neglected. Internal mechanisms that maintained balanced carbon flows were strongly impacted by river discharge and were only apparent by separately quantifying channel and shoal fluxes. Notably, metabolic responses of the shoal to river forcing outweighed the responses of the channel, and the net impact was contrary to prior relationships derived from synthesis of lower-resolution carbon budgets. Our budget demonstrates that resolution of carbon fluxes at appropriate scales, including channel-shoal and diel variability, is critical to characterizing ecosystem function and the fate of carbon within the river-ocean continuum

Posttraumatic stress symptoms and interpersonal processes in burn survivors and their partners

Background: A burn event can elicit symptoms of posttraumatic stress disorder (PTSD) in survivors and their partners and may impact the way these couple members interact with each other. They may try to protect each other from further emotional distress by avoiding talking about the burn event, but they may also show concern towards each other. Objective: The aim of this study was to investigate bidirectional relationships between survivor’s and partner’s PTSD symptoms and two interpersonal processes: partner-oriented ‘self-regulation’, which is avoidance-oriented, and ‘expressed concern’, which is approach-oriented. Method: In this longitudinal multi-centre study, 119 burn survivors and their partners participated. Measures of PTSD symptoms, self-regulation, and expressed concern were administered in the acute phase following the burns, and follow-ups took place up to 18 months postburn. Intra- and interpersonal effects were examined in a random intercept cross-lagged panel model. Exploratory effects of burn severity were also investigated. Results: Within individuals, survivor’s expressed concern predicted later higher levels of survivor’s PTSD symptoms. In their partners, self-regulation and PTSD symptoms reinforced each other in the early phase postburn. Between the two couple members, partner’s expressed concern predicted later lower levels of survivor’s PTSD symptoms. Exploratory regression analyses showed that burn severity moderated the effect of survivor’s self-regulation on survivor’s PTSD symptoms, indicating that self-regulation was continuously related to higher levels of PTSD symptoms over time within more severely burned survivors, but not in less severely burned survivors. Conclusion: PTSD symptoms and self-regulation reinforced each other in partners and possibly also in more severely burned survivors. Partner’s expressed concern was related to lower levels of survivor’s PTSD symptoms, whereas survivor’s expressed concern was related to higher levels of survivor’s PTSD symptoms. These findings emphasize the importance of screening for and monitoring PTSD symptoms in burn survivors and their partner and of encouraging couple’s self-disclosure

Bio-Psychological Predictors of Acute and Protracted Fatigue After Burns: A Longitudinal Study

Objective: Fatigue after burns is often attributed to the hyperinflammatory and hypermetabolic response, while it may be best understood from a bio-psychological perspective, also involving the neuro-endocrine system. This longitudinal multi-center study examined the course of fatigue up to 18 months postburn. The contribution of bio-psychological factors, including burn severity, pain, and acute PTSD symptoms, to the course and persistence of fatigue was studied in a multifactorial model. Methods: Participants were 247 adult burn survivors. Fatigue symptoms were assessed with the Multidimensional Fatigue Inventory during the acute phase and subsequently at 3, 6, 12, and 18 months postburn, and were compared to population norms. Age, gender, burn severity, acute PTSD symptoms and pain were assessed as potential predictors of fatigue over time in a latent growth model. Results: At 18 months postburn, 46% of the burn survivors reported fatigue, including 18% with severe fatigue. In the acute phase, higher levels of fatigue were related to multiple surgeries, presence of pain, and higher levels of acute PTSD symptoms. Fatigue gradually decreased over time with minor individual differences in rate of decrease. At 18 months, pain and acute PTSD symptoms remained significant predictors of fatigue levels. Conclusions: Protracted fatigue after burns was found in almost one out of five burn survivors and was associated with both pain and acute PTSD symptoms. Early detection of PTSD symptoms and early psychological interventions aimed at reducing PTSD symptoms and pain may be warranted to reduce later fatigue symptoms

Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial

Introduction: In ES-SCLC patients with residual intrathoracic disease after first-line chemotherapy, the addition of thoracic radiotherapy reduces the risk of intrathoracic recurrence, and improves 2-year survival. To identify patient subgroups for future trials investigating higher dose (extra)thoracic radiotherapy, we investigated the prognostic importance of number and sites of metastases in patients included in the CREST trial. Materials/methods: Additional data on sites and numbers of metastases were collected from individual records of 260 patients from the top 9 recruiting centers in the randomized CREST trial (53% of 495 study patients), which compared thoracic radiotherapy (TRT) to no TRT in ES-SCLC patients after any response to chemotherapy. All patients received prophylactic cranial irradiation. Results: The clinical characteristics and outcomes of the 260 patients analyzed here did not differ significantly from that of the other 235 patients included in the CREST trial, except that fewer patients had a WHO = 0 performance status (24% vs 45%), and a higher proportion had WHO = 2 (15% vs 5%; p <0.0001). No distant metastases were recorded in 5%, 39% had metastases confined to one organ, 34% to two, and 22% to three or more organ sites. Metastases were present in the liver (47%), bone (40%), lung (28%), extrathoracic (non-supraclavicular) lymph nodes (19%), supraclavicular nodes (18%), adrenals (17%) and other sites (12%). The OS (p = 0.02) and PFS (p = 0.04) were significantly better in patients with 2 or fewer metastases, with OS significantly worse if liver (p = 0.03) and/or bone metastases (p= 0.04) were present. Discussion: This analysis of patients recruited from the top 9 accruing centers in the CREST trial suggests that future studies evaluating more intensive thoracic and extra-thoracic radiotherapy in ES-SCLC should focus on patients with fewer than 3 distant metastases. (C) 2017 The Author(s). Published by Elsevier Ireland Ltd

C-Met targeted fluorescence molecular endoscopy in Barrett's esophagus patients and identification of outcome parameters for phase-I studies

Fluorescence molecular endoscopy (FME) is an emerging technique in the field of gastroenterology that holds potential to improve diagnosis and guide therapy, by serving as a ‘red-flag’ endoscopic imaging technique. Here, we investigated the safety, feasibility and optimal method of administration of EMI-137, targeting c-Met, during FME in Barrett’s Esophagus (BE) and report several outcome parameters for early phase FME studies. Methods: FME was performed in 15 Barrett’s neoplasia patients. EMI-137 was administered to three cohorts of five patients: 0.13 mg/kg intravenously (IV); 0.09 mg/kg IV or topically at a dose of 200 µg/cm BE (n=1) or 100 µg/cm BE (n=4). Fluorescence was visualized in vivo, quantified in vivo using multi-diameter single-fiber reflectance, single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlated to histopathology and immunohistochemistry. EMI-137 localization was assessed using fluorescence microscopy. Results: FME using different IV and topical doses o

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance:A retrospective, single-center study and the generation of www.emergencyprotocol.net

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD

Body surface potential mapping detects early disease onset in plakophilin-2-pathogenic variant carriers

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited cardiac disease. Early detection of disease and risk stratification remain challenging due to heterogeneous phenotypic expression. The standard configuration of the 12 lead electrocardiogram (ECG) might be insensitive to identify subtle ECG abnormalities. We hypothesized that body surface potential mapping (BSPM) may be more sensitive to detect subtle ECG abnormalities. METHODS AND RESULTS: We obtained 67 electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carriers and control subjects. Subject-specific computed tomography/magnetic resonance imaging based models of the heart/torso and electrode positions were created. Cardiac activation and recovery patterns were visualized with QRS- and STT-isopotential map series on subject-specific geometries to relate QRS-/STT-patterns to cardiac anatomy and electrode positions. To detect early signs of functional/structural heart disease, we also obtained right ventricular (RV) echocardiographic deformation imaging. Body surface potential mapping was obtained in 25 controls and 42 PKP2-pathogenic variant carriers. We identified five distinct abnormal QRS-patterns and four distinct abnormal STT-patterns in the isopotential map series of 31/42 variant carriers. Of these 31 variant carriers, 17 showed no depolarization or repolarization abnormalities in the 12 lead ECG. Of the 19 pre-clinical variant carriers, 12 had normal RV-deformation patterns, while 7/12 showed abnormal QRS- and/or STT-patterns. CONCLUSION: Assessing depolarization and repolarization by BSPM may help in the quest for early detection of disease in variant carriers since abnormal QRS- and/or STT-patterns were found in variant carriers with a normal 12 lead ECG. Because electrical abnormalities were observed in subjects with normal RV-deformation patterns, we hypothesize that electrical abnormalities develop prior to functional/structural abnormalities in ARVC

Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy:nationwide, observational cohort study

Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator.Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated.Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P &lt; 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P &lt; 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy.Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adequate treatment of complications and use of neoadjuvant treatment may improve oncological outcomes.</p

Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease

Background: Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for endocrine resistant breast cancer. Materials & methods: Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis. Results: A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2 (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen. Conclusions: This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance