The relationship between quality of life (EORTC QLQ-C30) and survival in patients with gastro-oesopohageal cancer

It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and survival in patients with gastro-oesophageal cancer. Patients presenting with gastric or oesophageal cancer, staged using the UICC tumour node metastasis (TNM) classification and who received either potentially curative surgery or palliative treatment between November 1997 and December 2002 (n=152) participated in a quality of life study, using the EORTC QLQ-C30 core questionnaire. On univariate analysis, age (P < 0.01), tumour length (P < 0.0001), TNM stage (P<0.0001), weight loss (P<0.0001), dysphagia score (P<0.001), performance status (P<0.1) and treatment (P<0.0001) were significantly associated with cancer-specific survival. EORTC QLQ-C30, physical functioning (P<0.0001), role functioning (P<0.001), cognitive functioning (P<0.01), social functioning (P<0.0001), global quality of life (P<0.0001), fatigue (P<0.0001), nausea/vomiting (P<0.01), pain (P<0.001), dyspnoea (P<0.0001), appetite loss (P<0.0001) and constipation (P<0.05) were also significantly associated with cancer-specific survival. On multivariate survival analysis, tumour stage (P<0.0001), treatment (P<0.001) and appetite loss (P<0.0001) were significant independent predictors of cancer-specific survival. The present study highlights the importance of quality of life (EORTC QLQ-C30) measures, in particular appetite loss, as a prognostic factor in these patients

Large amplitude solitary waves in and near the Earth's magnetosphere, magnetopause and bow shock: Polar and Cluster observations

International audienceSolitary waves with large electric fields (up to 100's of mV/m) have been observed throughout the magnetosphere and in the bow shock. We discuss observations by Polar at high altitudes ( ~ 4-8 RE ), during crossings of the plasma sheet boundary and cusp, and new measurements by Polar at the equatorial magnetopause and by Cluster near the bow shock, in the cusp and at the plasma sheet boundary. We describe the results of a statistical study of electron solitary waves observed by Polar at high altitudes. The mean solitary wave duration was ~ 2 ms. The waves have velocities from ~ 1000 km/s to > 2500 km/s. Observed scale sizes (parallel to the magnetic field) are on the order of 1-10lD, with eF/kTe from ~ 0.01 to O(1). The average speed of solitary waves at the plasma sheet boundary is faster than the average speed observed in the cusp and at cusp injections. The amplitude increases with both velocity and scale size. These observations are all consistent with the identification of the solitary waves as electron hole modes. We also report the discovery of solitary waves at the magnetopause, observed in Polar data obtained at the subsolar equatorial magnetopause. Both positive and negative potential structures have been observed with amplitudes up to ~ 25 mV/m. The velocities range from 150 km/s to >2500 km/s, with scale sizes the order of a kilometer (comparable to the Debye length). Initial observations of solitary waves by the four Cluster satellites are utilized to discuss the scale sizes and time variability of the regions where the solitary waves occur. Preliminary results from the four Cluster satellites have given a glimpse of the spatial and temporal variability of the occurrence of solitary waves and their association with other wave modes. In all the events studied, significant differences were observed in the waveforms observed simultaneously at the four locations separated by ~ 1000 km. When solitary waves were seen at one satellite, they were usually also seen at the other satellites within an interval of a few seconds. In association with an energetic electron injection and a highly compressed magnetosphere, Cluster has observed the largest amplitude solitary waves (>750 mV/m) ever reported in the outer magnetosphere

An elevated C-reactive protein concentration, prior to surgery, predicts poor cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of tumours. The aim of the present study was to examine the relationship between clinico-pathological status, preoperative C-reactive protein concentration and cancer-specific survival in patients undergoing resection for gastro-oesophageal cancer. One hundred and twenty patients attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow, who were selected for potentially curative surgery, were included in the study. Laboratory measurements of haemoglobin, white cell, lymphocyte and platelet counts, albumin and C-reactive protein were carried out at the time of diagnosis. All patients underwent en-bloc resection with lymphadenectomy and survived at least 30 days following surgery. On multivariate analysis, only the positive to total lymph node ratio (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.44–2.84, P<0.001) and preoperative C-reactive protein concentration (HR 3.53, 95% CI 1.88–6.64, P<0.001) were independent predictors of cancer-specific survival. The patient group with no evidence of a preoperative systemic inflammatory response (C-reactive protein ⩽10 mg l−1) had a median survival of 79 months compared with 19 months in the elevated systemic inflammatory response group (P<0.001). The results of the present study indicate that in patients selected to undergo potentially curative resection for gastro-oesophageal cancer, the presence of an elevated preoperative C-reactive protein concentration is an independent predictor of poor cancer-specific survival

Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer

BACKGROUND: Advances in the treatment of metastatic colorectal cancer (mCRC) in the last decade have significantly improved survival; however, simple biomarkers to predict response or toxicity have not been identified, which are applicable to all community oncology settings worldwide. The use of inflammatory markers based on differential white-cell counts, such as the neutrophil/ lymphocyte ratio (NLR), may be simple and readily available biomarkers. METHODS: Clinical information and baseline laboratory parameters were available for 349 patients, from two independent cohorts, with unresectable mCRC receiving first-line palliative chemotherapy. Associations between baseline prognostic variables, including inflammatory markers such as the NLR and tumour response, progression and survival were investigated. RESULTS: In the training cohort, combination-agent chemotherapy (P ¼ 0.001) and NLRp5 (P ¼ 0.003) were associated with improved clinical benefit. The ECOG performance status X1 (P ¼ 0.002), NLR45 (P ¼ 0.01), hypoalbuminaemia (P ¼ 0.03) and single-agent chemotherapy (Po0.0001) were associated with increased risk of progression. The ECOG performance status X1 (P ¼ 0.004) and NLR45 (P ¼ 0.002) predicted worse overall survival (OS). The NLR was confirmed to independently predict OS in the validation cohort (Po0.0001). Normalisation of the NLR after one cycle of chemotherapy in a subset of patients resulted in improved progression-free survival (P ¼ 0.012). CONCLUSION: These results have highlighted NLR as a potentially useful clinical biomarker of systemic inflammatory response in predicting clinically meaningful outcomes in two independent cohorts. Results of this study have also confirmed the importance of a chronic systemic inflammatory response influencing clinical outcomes in patients with mCRC

Staging the tumour and staging the host: Pre-treatment combined Neutrophil Lymphocyte Ratio and modified Glasgow Prognostic Score is associated with overall survival in patients with oesophagogastric cancers undergoing treatment with curative intent

Background: This study examined whether an innate systemic inflammatory response (SIR) measured by combination neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) was associated with overall survival (OS) in patients with esophagogastric cancer (EC) undergoing neoadjuvant chemotherapy (NAC) followed by surgery. Methods: Patients diagnosed with EC, managed with NAC prior to surgery at a regional referral center, between January 2010 and December 2015, were included. The mGPS and NLR were calculated within 12 weeks before NAC. Patients were grouped by combined NLR/mGPS score into three groups of increasing SIR: NLR ≤ 3 (n = 152), NLR &gt; 3 + mGPS = 0 (n = 55), and NLR &gt; 3 + mGPS &gt; 0 (n = 32). Univariable and multivariable Cox regression was used to analyse OS. Results: Overall, 337 NAC patients were included, with 301 (89%) proceeding to surgery and 215 (64%) having R0 resection. There were 203 deaths, with a median follow-up of those alive at censor of 69 months (range 44–114). Higher combined NLR/mGPS score (n = 239) was associated with poorer OS independent of clinical stage and performance status (hazard ratio 1.28, 95% confidence interval 1.02–1.61; p = 0.032), higher rate of progression on NAC (7% vs. 7% vs. 19%; p = 0.003), and lower proportion of eventual resection (80% vs. 84% vs. 53%; p = 0.003). Conclusions: The combined NLR/mGPS score was associated with OS and initial treatment outcomes in patients undergoing NAC prior to surgery for EC, stratifying survival in addition to clinical staging and performance status. The host SIR may be a useful adjunct to multidisciplinary decision making

Canine CNGA3 Gene Mutations Provide Novel Insights Into Human Achromatopsia-Associated Channelopathies and Treatment

Cyclic nucleotide-gated (CNG) ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM). ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivoand channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD) simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ) domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivochannels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients

Anthropological contributions to historical ecology: 50 questions, infinite prospects.

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural

The Galactic Center Black Hole Laboratory

The super-massive 4 million solar mass black hole Sagittarius~A* (SgrA*) shows flare emission from the millimeter to the X-ray domain. A detailed analysis of the infrared light curves allows us to address the accretion phenomenon in a statistical way. The analysis shows that the near-infrared flare amplitudes are dominated by a single state power law, with the low states in SgrA* limited by confusion through the unresolved stellar background. There are several dusty objects in the immediate vicinity of SgrA*. The source G2/DSO is one of them. Its nature is unclear. It may be comparable to similar stellar dusty sources in the region or may consist predominantly of gas and dust. In this case a particularly enhanced accretion activity onto SgrA* may be expected in the near future. Here the interpretation of recent data and ongoing observations are discussed.Comment: 30 pages - 7 figures - accepted for publication by Springer's "Fundamental Theories of Physics" series; summarizing GC contributions of 2 conferences: 'Equations of Motion in Relativistic Gravity' at the Physikzentrum Bad Honnef, Bad Honnef, Germany, (Feb. 17-23, 2013) and the COST MP0905 'The Galactic Center Black Hole Laboratory' Granada, Spain (Nov. 19 - 22, 2013

The relationship between computed tomography-derived sarcopenia, cardiopulmonary exercise testing performance, systemic inflammation, and survival in good performance status patients with oesophago-gastric cancer undergoing neoadjuvant treatment

Background: Thought to capture the nutritional and functional reserve of the cancer patient, whether the computed tomography (CT)-derived sarcopenia score (CT-SS) has complimentary prognostic value to commonly utilized pre-treatment host assessments in patients with oesophago-gastric (OG) cancer is unknown. The aim of the present study was to examine if the CT-SS can stratify survival in OG cancer patients with good performance status [Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0/1]. Furthermore, if the CT-SS had complimentary prognostic value to cardiopulmonary exercise testing (CPET) performance and systemic inflammation. Methods: Consecutive patients with confirmed OG cancer and good performance status, who received neoadjuvant chemotherapy (NAC) with a view to surgical resection with curative intent, between 1 January 2010 and 31 December 2015, within NHS Greater Glasgow and Clyde (NHSGGC) and NHS Forth Valley (NHSFV), were identified from a prospectively maintained database. CT-SSs were grouped as 0/1/2. CPET variables recorded included VO2 anaerobic threshold (AT) and peak. Systemic inflammatory response was determined by modified Glasgow prognostic score (mGPS) and neutrophil/lymphocyte ratio (NLR). Associations between categorical variables were examined using χ2 test and binary logistics regression analysis. Results: A total of 232 patients met the inclusion criteria. 75% (n = 174) of patients were male, 54% (n = 126) were 65 years or older, and 60% (n = 139) were overweight [body mass index (BMI) ≥25 kg/m2]; 33% (n = 77) of patients had CT-SS ≥ 1, 36% (n = 83) had a low VO2 AT (≤11 ml/kg/min), and 57% (n = 132) had a low VO2 peak (≤19 ml/kg/min). Of the 200 patients who had pre-NAC bloods facilitating calculation of the mGPS, 28% (n = 55) had mGPS ≥ 1. Of the 211 patients who had pre-NAC bloods facilitating calculation of NLR, 38% (n = 80) had an NLR ≥ 3; 82% (n = 190) and 53% (n = 122) were alive at 1 and 3 years post-NAC, respectively. On univariate analysis, CT-SS was significantly associated with sex (P &lt; 0.05), histological cell type (P &lt; 0.05), low VO2 AT (P &lt; 0.05), low VO2 peak (P &lt; 0.05), BMI (P &lt; 0.05), mGPS (P &lt; 0.05), and 3-year survival (P &lt; 0.05). On multivariate analysis, tumour, node, and metastasis (TNM) stage (P &lt; 0.05) and CT-SS (P &lt; 0.05) remained significantly associated with 3-year survival. CT-SS was significantly associated with 3-year survival in patients who had mGPS 0 (P &lt; 0.05), but not low VO2 AT (P = 0.066) or peak (P = 0.065). Conclusion: The CT-SS would appear to capture the nutritional and functional reserve of the patient and is a useful objective measure for stratifying long-term survival in patients with good performance status undergoing potentially curative treatment for OG cancer