Distributions of total and size-fractionated particulate 210Po and 210Pb activities along the North Atlantic GEOTRACES GA01 transect: GEOVIDE cruise

Vertical distributions of total and particulate polonium-210 (210Po) and lead-210 (210Pb) activities in the water column were measured at 11 stations in the North Atlantic during the GEOTRACES GA01 transect: GEOVIDE cruise in May–June 2014. Total 210Po activity was on average 24% lower than 210Pb activity in the upper 100m, and it was closer to unity in the mesopelagic (100–1000m). The partitioning coefficients (Kd) along the transect suggest the preferential association of 210Po relative to 210Pb onto particles. The prominent role of small particles in sorption was confirmed by the observation that over 80% of the particulate radionuclide activity was on small particles. To account for the observed surface water 210Po∕210Pb disequilibria, particulate radionuclide activities and export of both small (1–53µm) and large ( \u3e 53µm) particles must be considered. A comparison between the GEOVIDE total particulate 210Po∕210Pb activity ratios (ARs) and the ratios in previous studies revealed a distinct geographic distribution, with lower particulate ARs in the high-latitude North Atlantic (including this study) and Arctic in relation to all other samples. For the samples where apparent oxygen utilization (AOU) was calculated at the same depth and time as the 210Po∕210Pb AR (40 stations including this study), there was a two-phase correlation between the total particulate AR and AOU, likely reflecting the nature of the particles and demonstrating the forces of remineralization and radionuclide decay from particles as they age

Radionuclides as Ocean Tracers

Radionuclides, both from natural and anthropogenic origin, are powerful ocean tracers that provide key information on fluxes, pathways and time scales of marine processes. Their added value compared to hydrographic parameters (e.g., temperature and salinity) relies either on their known rates of radioactive decay and production or on their time-variable releases from sources. Both aspects introduce a temporal dimension that allows quantifying rates or time scales of marine processes. Their wide range of half-lives and historical inputs, together with their physicochemical characteristics allow tracing a broad spectrum of marine processes. This chapter aims at providing an overview of the application of radionuclides as tracers of ocean processes. The chapter is structured in four sections: The first part reviews the main principles of radioactivity and the origin of radionuclides. The second section introduces the key aspects that allow using radionuclides as ocean tracers, followed by (third section) three real and contemporary instructive examples that cover different marine processes and require radionuclides with specific properties: i) thorium-234/uranium-238 (234Th/238U) pair to quantify the biological pump, ii) radium (Ra) isotopes to estimate the magnitude of submarine groundwater discharge, and iii) iodine-129 (129I) to investigate the large-scale ocean circulation. Finally, this chapter provides a summary of the different methods and techniques used to measure radionuclides in seawater

Differences in macular vessel density in the superficial plexus across cognitive impairment : the NORFACE cohort

Optical coherence tomography angiography (OCT-A) allows the detection of retinal vessel density (VD) loss, which is a reflection of brain vascular pathology. We aimed to investigate differences in macular VD in the superficial plexus in a large cohort of individuals cognitively unimpaired (CU), with mild cognitive impairment due to Alzheimer's disease (MCI-AD), MCI due to cerebrovascular pathology (MCI-Va), probable Alzheimer's disease dementia (ADD) and Vascular Dementia (VaD). Clinical, demographical, ophthalmological and OCT-A data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences of macular VD in four quadrants (superior, nasal, inferior and temporal) among the five diagnostic groups were assessed in a multivariate regression model, adjusted by age, sex, education, hypertension, diabetes mellitus, heart disease and stroke. The study cohort comprised 672 participants: 128 CU, 120 MCI-AD, 111 MCI-Va, 257 ADD and 56 VaD. Regression analysis showed a significantly higher VD in the temporal quadrant in MCI-AD compared to CU participants (49.05 ± 4.91 vs 47.27 ± 4.17, p = 0.02, d = 0.40), and a significantly lower VD in the inferior quadrant in MCI-Va compared to CU participants (48.70 ± 6.57 vs 51.27 ± 6.39, p = 0.02, d = 0.40). Individuals with heart disease presented significantly lower VD in the inferior quadrant than those without (p = 0.01). The interaction of sex and diagnosis had no effect in differentiating VD. Mini-Mental State Examination (MMSE) scores were not correlated to VD (all r 0.07). In conclusion, our study showed that the MCI-AD and MCI-Va groups had significant differences in macular VD in opposite directions in the temporal and inferior quadrants, respectively, compared to CU participants, suggesting that macular VD might be able to differentiate two pathogenic pathways (AD- and cerebrovascular-related) in early stages of cognitive decline

2-phenylethynesulphonamide (PFT-μ) enhances the anticancer effect of the novel hsp90 inhibitor NVP-AUY922 in melanoma, by reducing GSH levels

Heat shock proteins (HSPs), are molecular chaperones that assist the proper folding of nascent proteins. This study aims to evaluate the antitumour effects of the hsp90 inhibitor NVP-AUY922 in melanoma, both in vitro and in vivo. Our results show that NVP-AUY922 inhibits melanoma cell growth in vitro, with down regulation of multiple signalling pathways involved in melanoma progression such as NF-KB and MAPK/ERK. However, NVP-AUY922 was unable to limit tumour growth in vivo. Cotreatment of A375M xenografts with NVP-AUY922 and PFT-l, a dual inhibitor of both hsp70 and autophagy, induced a synergistic increase of cell death in vitro, and delayed tumour formation in A375M xenografts. PFT-l depleted cells from the reduced form of glutathione (GSH) and increased oxidative stress. The oxidative stress induced by PFT-l further enhanced NVP-AUY922-induced cytotoxic effects. These data suggest a potential therapeutic role for NVP-AUY922 used in combination with PFT-l, in melanoma

Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer’s disease

Abstract The use of optical coherence tomography (OCT) has been suggested as a potential biomarker for Alzheimer’s Disease based on previously reported thinning of the retinal nerve fiber layer (RNFL) in Alzheimer’s disease’s (AD) and Mild Cognitive Impairment (MCI). However, other studies have not shown such results. 930 individuals (414 cognitively healthy individuals, 192 probable amnestic MCI and 324 probable AD) attending a memory clinic were consecutively included and underwent spectral domain OCT (Maestro, Topcon) examinations to assess differences in peripapillary RNFL thickness, using a design of high ecological validity. Adjustment by age, education, sex and OCT image quality was performed. We found a non-significant decrease in mean RNFL thickness as follows: control group: 100,20 ± 14,60 µm, MCI group: 98,54 ± 14,43 µm and AD group: 96,61 ± 15,27 µm. The multivariate adjusted analysis revealed no significant differences in mean overall (p = 0.352), temporal (p = 0,119), nasal (p = 0,151), superior (p = 0,435) or inferior (p = 0,825) quadrants between AD, MCI and control groups. These results do not support the usefulness of peripapillary RNFL analysis as a marker of cognitive impairment or in discriminating between cognitive groups. The analysis of other OCT measurements in other retinal areas and layers as biomarkers for AD should be tested further

Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment : The NORFACE cohort

Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI). Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category. The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aβ1-42, p181-tau and t-tau measures were not correlated to VD (all r 0.13). Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

Background: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake. Aims: We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. Methods: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/-) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2. Results: Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02-1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months. Conclusions: Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 796706, and the Instituto de Salud Carlos III (ISCIII) grant PI19/00335 Acción Estratégica en Salud, integrated in the Spanish National R+D+I Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER-Una manera de hacer Europa") awarded to M.M. Funds were also obtained from donations from “La nit de l’Alzheimer”, a charity dinner initiative that takes place yearly as part of the “Festival Castell de Peralada” (2016-2018). The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project “Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer’s disease” under the leadership of C.H. Funds from Fundació ACE Institut Català de Neurociències Aplicades, Grifols, Life Molecular Imaging, Araclon Biotech, Alkahest, Laboratorio de análisis Echevarne and IrsiCaixa are supporting the FACEHBI study. These sponsors were not involved in the study design, data collection, analysis or interpretation. The sponsors have reviewed the manuscript and have given their approval

Starlikeness of Libera transformation (II) (Applications of Complex Function Theory to Differential Equations)

The GEOTRACES Intermediate Data Product 2017 (IDP2017) is the second publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2016. The IDP2017 includes data from the Atlantic, Pacific, Arctic, Southern and Indian oceans, with about twice the data volume of the previous IDP2014. For the first time, the IDP2017 contains data for a large suite of biogeochemical parameters as well as aerosol and rain data characterising atmospheric trace element and isotope (TEI) sources. The TEI data in the IDP2017 are quality controlled by careful assessment of intercalibration results and multi-laboratory data comparisons at crossover stations. The IDP2017 consists of two parts: (1) a compilation of digital data for more than 450 TEIs as well as standard hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing an on-line atlas that includes more than 590 section plots and 130 animated 3D scenes. The digital data are provided in several formats, including ASCII, Excel spreadsheet, netCDF, and Ocean Data View collection. Users can download the full data packages or make their own custom selections with a new on-line data extraction service. In addition to the actual data values, the IDP2017 also contains data quality flags and 1-σ data error values where available. Quality flags and error values are useful for data filtering and for statistical analysis. Metadata about data originators, analytical methods and original publications related to the data are linked in an easily accessible way. The eGEOTRACES Electronic Atlas is the visual representation of the IDP2017 as section plots and rotating 3D scenes. The basin-wide 3D scenes combine data from many cruises and provide quick overviews of large-scale tracer distributions. These 3D scenes provide geographical and bathymetric context that is crucial for the interpretation and assessment of tracer plumes near ocean margins or along ridges. The IDP2017 is the result of a truly international effort involving 326 researchers from 25 countries. This publication provides the critical reference for unpublished data, as well as for studies that make use of a large cross-section of data from the IDP2017. This article is part of a special issue entitled: Conway GEOTRACES - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González

Development of a prediction model for postoperative pneumonia A multicentre prospective observational study

BACKGROUND Postoperative pneumonia is associated with increased morbidity, mortality and costs. Prediction models of pneumonia that are currently available are based on retrospectively collected data and administrative coding systems. OBJECTIVE To identify independent variables associated with the occurrence of postoperative pneumonia. DESIGN A prospective observational study of a multicentre cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe database). SETTING Sixty-three hospitals in Europe. PATIENTS Patients undergoing surgery under general and/or regional anaesthesia during a 7-day recruitment period. MAIN OUTCOME MEASURE The primary outcome was postoperative pneumonia. Definition: the need for treatment with antibiotics for a respiratory infection and at least one of the following criteria: new or changed sputum; new or changed lung opacities on a clinically indicated chest radiograph; temperature more than 38.3 degrees C; leucocyte count more than 12 000 mu l(-1). RESULTS Postoperative pneumonia occurred in 120 out of 5094 patients (2.4%). Eighty-two of the 120 (68.3%) patients with pneumonia required ICU admission, compared with 399 of the 4974 (8.0%) without pneumonia (P < 0.001). We identified five variables independently associated with postoperative pneumonia: functional status [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.58 to 3.12], pre-operative SpO(2) values while breathing room air (OR 0.83, 95% CI 0.78 to 0.84), intra-operative colloid administration (OR 2.97, 95% CI 1.94 to 3.99), intra-operative blood transfusion (OR 2.19, 95% CI 1.41 to 4.71) and surgical site (open upper abdominal surgery OR 3.98, 95% CI 2.19 to 7.59). The model had good discrimination (c-statistic 0.89) and calibration (Hosmer-Lemeshow P = 0.572). CONCLUSION We identified five variables independently associated with postoperative pneumonia. The model performed well and after external validation may be used for risk stratification and management of patients at risk of postoperative pneumonia