Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-ß and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes.

Transient ice loss in the Patagonia Icefields during the 2015-2016 El Niño event.

The Patagonia Icefields (PIF) are the largest non-polar ice mass in the southern hemisphere. The icefields cover an area of approximately 16,500 km2 and are divided into the northern and southern icefields, which are ~ 4000 km2 and ~ 12,500 km2, respectively. While both icefields have been losing mass rapidly, their responsiveness to various climate drivers, such as the El Niño-Southern Oscillation, is not well understood. Using the elastic response of the earth to loading changes and continuous GPS data we separated and estimated ice mass changes observed during the strong El Niño that started in 2015 from the complex hydrological interactions occurring around the PIF. During this single event, our mass balance estimates show that the northern icefield lost ~ 28 Gt of mass while the southern icefield lost ~ 12 Gt. This is the largest ice loss event in the PIF observed to date using geodetic data.

Cardiac Magnetic Resonance at 3.0 T in Patients With C282Y Homozygous Hereditary Hemochromatosis: Superiority of Radial and Circumferential Strain Over Cardiac T2* Measurements at Baseline and at Post Venesection Follow-up.

BACKGROUND: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment. MATERIALS AND METHODS: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software. RESULTS: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) ( P =0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) ( P =0.001) and mean global circumferential strain improved, decreasing from -15.7 (range: -11.1 to -19.2) to -17.1 (range: -13.0 to -20.1) ( P =0.001). CONCLUSION: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment.

Microwave Radiometry at Frequencies From 500 to 1400 MHz: An Emerging Technology for Earth Observations.

Microwave radiometry has provided valuable spaceborne observations of Earth's geophysical properties for decades. The recent SMOS, Aquarius, and SMAP satellites have demonstrated the value of measurements at 1400 MHz for observing surface soil moisture, sea surface salinity, sea ice thickness, soil freeze/thaw state, and other geophysical variables. However, the information obtained is limited by penetration through the subsurface at 1400 MHz and by a reduced sensitivity to surface salinity in cold or wind-roughened waters. Recent airborne experiments have shown the potential of brightness temperature measurements from 500-1400 MHz to address these limitations by enabling sensing of soil moisture and sea ice thickness to greater depths, sensing of temperature deep within ice sheets, improved sensing of sea salinity in cold waters, and enhanced sensitivity to soil moisture under vegetation canopies. However, the absence of significant spectrum reserved for passive microwave measurements in the 500-1400 MHz band requires both an opportunistic sensing strategy and systems for reducing the impact of radio-frequency interference. Here, we summarize the potential advantages and applications of 500-1400 MHz microwave radiometry for Earth observation and review recent experiments and demonstrations of these concepts. We also describe the remaining questions and challenges to be addressed in advancing to future spaceborne operation of this technology along with recommendations for future research activities.

The Protein Secretome Is Altered in Rectal Cancer Tissue Compared to Normal Rectal Tissue, and Alterations in the Secretome Induce Enhanced Innate Immune Responses.

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy; however, only ~22% of patients achieve a complete response, and resistance mechanisms are poorly understood. The role of inflammation and immune cell biology in this setting is under-investigated. In this study, we profiled the inflammatory protein secretome of normal (non-cancer) (n = 8) and malignant rectal tissue (n = 12) pre- and post-radiation in human ex vivo explant models and examined the influence of these untreated and treated secretomes on dendritic cell biology (n = 8 for cancer and normal). These resultant profiles were correlated with patient clinical characteristics. Nineteen factors were secreted at significantly higher levels from the rectal cancer secretome when compared to the normal rectal secretome; Flt-1, P1GF, IFN-γ, IL-6, IL-10, CCL20, CCL26, CCL22, CCL3, CCL4, CCL17, GM-CSF, IL-12/IL-23p40, IL-17A, IL-1α, IL-17A/F, IL-1RA, TSLP and CXCL10 (p < 0.05). Radiation was found to have differential effects on normal rectal tissue and rectal cancer tissue with increased IL-15 and CCL22 secretion following radiation from normal rectal tissue explants (p < 0.05), while no significant alterations were observed in the irradiated rectal cancer tissue. Interestingly, however, the irradiated rectal cancer secretome induced the most potent effect on dendritic cell maturation via upregulation of CD80 and PD-L1. Patient's visceral fat area correlated with secreted factors including CCL20, suggesting that obesity status may alter the tumour microenvironment (TME). These results suggest that radiation does not have a negative effect on the ability of the rectal cancer TME to induce an immune response. Understanding these responses may unveil potential therapeutic targets to enhance radiation response and mitigate normal tissue injury. Tumour irradiation in this cohort enhances innate immune responses, which may be harnessed to improve patient treatment outcome.

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model.

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBE-induction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.

Observing Rivers With Varying Spatial Scales.

The National Aeronautics and Space Administration/Centre national d'études spatiales Surface Water and Ocean Topography (SWOT) mission will estimate global river discharge using remote sensing. Synoptic remote sensing data extend in situ point measurements but, at any given point, are generally less accurate. We address two questions: (1)What are the scales at which river dynamics can be observed, given spatial sampling and measurement noise characteristics? (2) Is there an equation whose variables are the averaged hydraulic quantities obtained by remote sensing and which describes the dynamics of spatially averaged rivers? We use calibrated hydraulic models to examine the power spectra of the different terms in the momentum equation and conclude that the measurement of river slope sets the scale at which rivers can be observed. We introduce the reach-averaged Saint Venant equations that involve only observable hydraulic variations and which parametrize within-reach variability with a variability index that multiplies the friction coefficient and leads to an increased "effective" friction coefficient. An exact expression is derived for the increase in the effective friction coefficient, and we propose an approximation that requires only estimates of the hydraulic parameter variances. We validate the results using a large set of hydraulic models and find that the approximated variability index is most faithful when the river parameters obey lognormal statistics. The effective friction coefficient, which can vary from a few percent to more than 50% of the point friction coefficient, is proportional to the riverbed elevation variance and inversely proportional to the depth. This has significant implications for estimating discharge from SWOT  data.

Adenocarcinoma of the lung: from BAC to the future.

Adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma are relatively new classification entities which replace the now retired term, bronchoalveolar carcinoma (BAC). The radiographic appearance of these lesions ranges from pure, ground glass nodules to large, solid masses. A thorough understanding of the new classification is essential to radiologists who work with MDT colleagues to provide accurate staging and treatment. A 2-year review was performed of all surgically resected cases of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma in our institution. Cases are broken down by age, gender, tumour type and tumour location. A pictorial review is presented to illustrate the radiologic and pathologic features of each entity.

Chemotherapy and repeat resection abrogate the prognostic value of neutrophil lymphocyte ratio in colorectal liver metastases.

BACKGROUND: Evolution in surgical and oncological management of CRLM has called into question the utility of clinical risk scores. We sought to establish if neutrophil lymphocyte ratio (NLR) has a prognostic role in this patient cohort. METHODS: From 2005 to 2015,379 hepatectomies were performed for CRLM, 322 underwent index hepatectomy, 57 s hepatectomies were performed. Clinicopathological data were obtained from a prospectively maintained database. Variables associated with longterm survival following index and second hepatectomy were identified by Cox regression analyses and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Following index hepatectomy 1-,3-and 5-year survival was 90.7%, 68.1% and 48.6%. Major resection, positive margins and >5 tumours were negatively associated with survival. Those with elevated NLR(>5) had a median survival of 55 months, compared to 70 months with lower NLR(p = 0.027). Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (p = 0.93). Furthermore, NLR >5 had no impact on prognosis following repeat hepatectomy. Tumour diameter >5 cm (p = 0.04) was the sole predictor of poorer survival (p = 0.049). CONCLUSION: Despite elevated NLR correlating with shorter survival following index hepatectomy, this effect is negated by neoadjuvant chemotherapy and second hepatectomy for recurrent disease. This data would not support the use of NLR in the preoperative decision algorithm for patients with CRLM.

Global Reconstruction of Naturalized River Flows at 2.94 Million Reaches.

Spatiotemporally continuous global river discharge estimates across the full spectrum of stream orders are vital to a range of hydrologic applications, yet they remain poorly constrained. Here we present a carefully designed modeling effort (Variable Infiltration Capacity land surface model and Routing Application for Parallel computatIon of Discharge river routing model) to estimate global river discharge at very high resolutions. The precipitation forcing is from a recently published 0.1° global product that optimally merged gauge-, reanalysis-, and satellite-based data. To constrain runoff simulations, we use a set of machine learning-derived, global runoff characteristics maps (i.e., runoff at various exceedance probability percentiles) for grid-by-grid model calibration and bias correction. To support spaceborne discharge studies, the river flowlines are defined at their true geometry and location as much as possible-approximately 2.94 million vector flowlines (median length 6.8 km) and unit catchments are derived from a high-accuracy global digital elevation model at 3-arcsec resolution (~90 m), which serves as the underlying hydrography for river routing. Our 35-year daily and monthly model simulations are evaluated against over 14,000 gauges globally. Among them, 35% (64%) have a percentage bias within ±20% (±50%), and 29% (62%) have a monthly Kling-Gupta Efficiency ≥0.6 (0.2), showing data robustness at the scale the model is assessed. This reconstructed discharge record can be used as a priori information for the Surface Water and Ocean Topography satellite mission's discharge product, thus named "Global Reach-level A priori Discharge Estimates for Surface Water and Ocean Topography". It can also be used in other hydrologic applications requiring spatially explicit estimates of global river flows.

Multivisceral Resection for Locally Invasive Colorectal Liver Metastases: Outcomes of a Matched Cohort Analysis.

Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections. METHODS: From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period. RESULTS: Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted. CONCLUSION: In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to -surgery with comparable morbidity and mortality rates to -isolated hepatectomy.

Spatial analysis of respiratory disease on an urbanized geothermal field.

Chronic exposure to hydrogen sulfide (H(2)S) in the parts per billion-parts per million range occurs in the population of Rotorua, a city built upon an actively degassing geothermal field in the Taupo Volcanic Zone, New Zealand. H(2)S is acutely toxic at high concentrations but little is understood of the health effects of chronic, low-level exposure. In Rotorua, H(2)S emissions and ambient concentrations are heterogeneous and approximately 30% of the greater urban area's population live upon or <4 km downwind of the geothermal field. Spatial analysis of disease incidence clustering using a spatial scan statistic is a powerful tool with which to investigate the spatial relationship which may exist between H(2)S and respiratory disease. This paper reports findings from a spatial cluster analysis of 11 years of hospital discharge data at the census area unit resolution. Results indicate that the relative risk (RR) of incidence of noninfectious respiratory diseases may be substantially higher among residents living in the geothermal area than have been reported previously. RR >5 for chronic obstructive pulmonary disease and its associated conditions are found in clusters which are spatially coincident with the geothermal field. Future work which investigates neurological and circulatory disease groups at the same or better spatial resolution may provide further insight into the chronic health effects of H(2)S exposure than these preliminary findings indicate.

Geothermal ground gas emissions and indoor air pollution in Rotorua, New Zealand.

The emission of toxic gases from the soil is a hazard in geothermal regions that are also urbanized because buildings constructed on geothermal ground may be subject to the ingress of gases from the soil directly into the structure. The Rotorua geothermal field, New Zealand, is extensively urbanized but to date no studies have evaluated the extent of the ground gas hazard. The main gases emitted are hydrogen sulphide (H2S) and carbon dioxide (CO2), both of which are highly toxic and denser than air. This paper reports preliminary findings from a study of selected buildings constructed in the gas anomaly area. Properties were investigated for evidence of ingress by H2S, CO2, and 222Rn, with a view to determine the means and rates of gas entry and the nature of any consequent hazard. H2S and CO2 were investigated using infrared active gas analysers and passive detector tubes left in place for 10-48 h. 222Rn was measured over a period of 3 months by poly-allyl diglycol carbonate sensors. Eight of the nine buildings studied were found to suffer problems with soil gases entering the indoor air through the structure. The primary means of gas entry was directly from the ground through the floors, walls, and subsurface pipes. Indoor vents were located and found emitting up to approximately 200 ppm H2S and approximately 15% CO2, concentrations high enough to present an acute respiratory hazard to persons close to the vent (e.g., children playing at floor level). In some properties, gas problems occurred despite preventative measures having been made during construction or during later renovations. Typically, these measures include the under-laying of concrete floors with a gas-proof butanol seal, under-floor ventilation systems or the installation of positive-pressure air conditioning. Recently constructed buildings (<10 years) with butanol seals were nevertheless affected by ground gas emissions, and we conclude that such measures are not always effective in the long term.

Effect of volcanic gas exposure on urine, blood, and serum chemistry.

AIMS: This pilot study tested the hypothesis that aluminium (Al), rubidium (Rb), arsenic (As), lead (Pb), mercury (Hg), fluorine (F), and chlorine (Cl), which are all known to be present in volcanic emissions, may be useful biological markers for occupational gas exposure in volcanologists. METHODS: Ten human subjects were exposed to fumarole gases on White Island, New Zealand, for approximately 20 minutes. Sulphur dioxide (SO2) exposure was recorded by personal monitoring tubes. Pre- and post-exposure urine, blood and serum samples (collected using standard protocols) were analysed in the pathology laboratory for trace element and halogen content. RESULTS: Average personal exposure was measured at <75 ppm SO2 and calculated at approximately 25 ppm HCl, approximately 8 ppm hydrogen fluoride (HF), approximately 1 ppm Al, approximately 0.1 ppb Rb and approximately 4 ppb Pb. These concentrations almost certainly exceed those usually found in occupational exposure settings. Advanced levels of urinary Al and Rb were found following gas exposure and were statistically significant in the population at p<0.005 and p<0.001, respectively. The other chemical elements that were analysed (urinary Cl, F, and Hg; blood Pb, and serum Al) did not show such patterns. CONCLUSIONS: It is possible that urinary Al and Rb may be useful markers for exposure, a hypothesis which should be followed up in future work.