Outcome Prediction of Consciousness Disorders in the Acute Stage Based on a Complementary Motor Behavioural Tool.

INTRODUCTION: Attaining an accurate diagnosis in the acute phase for severely brain-damaged patients presenting Disorders of Consciousness (DOC) is crucial for prognostic validity; such a diagnosis determines further medical management, in terms of therapeutic choices and end-of-life decisions. However, DOC evaluation based on validated scales, such as the Revised Coma Recovery Scale (CRS-R), can lead to an underestimation of consciousness and to frequent misdiagnoses particularly in cases of cognitive motor dissociation due to other aetiologies. The purpose of this study is to determine the clinical signs that lead to a more accurate consciousness assessment allowing more reliable outcome prediction. METHODS: From the Unit of Acute Neurorehabilitation (University Hospital, Lausanne, Switzerland) between 2011 and 2014, we enrolled 33 DOC patients with a DOC diagnosis according to the CRS-R that had been established within 28 days of brain damage. The first CRS-R assessment established the initial diagnosis of Unresponsive Wakefulness Syndrome (UWS) in 20 patients and a Minimally Consciousness State (MCS) in the remaining13 patients. We clinically evaluated the patients over time using the CRS-R scale and concurrently from the beginning with complementary clinical items of a new observational Motor Behaviour Tool (MBT). Primary endpoint was outcome at unit discharge distinguishing two main classes of patients (DOC patients having emerged from DOC and those remaining in DOC) and 6 subclasses detailing the outcome of UWS and MCS patients, respectively. Based on CRS-R and MBT scores assessed separately and jointly, statistical testing was performed in the acute phase using a non-parametric Mann-Whitney U test; longitudinal CRS-R data were modelled with a Generalized Linear Model. RESULTS: Fifty-five per cent of the UWS patients and 77% of the MCS patients had emerged from DOC. First, statistical prediction of the first CRS-R scores did not permit outcome differentiation between classes; longitudinal regression modelling of the CRS-R data identified distinct outcome evolution, but not earlier than 19 days. Second, the MBT yielded a significant outcome predictability in the acute phase (p<0.02, sensitivity>0.81). Third, a statistical comparison of the CRS-R subscales weighted by MBT became significantly predictive for DOC outcome (p<0.02). DISCUSSION: The association of MBT and CRS-R scoring improves significantly the evaluation of consciousness and the predictability of outcome in the acute phase. Subtle motor behaviour assessment provides accurate insight into the amount and the content of consciousness even in the case of cognitive motor dissociation.

Reasoning on the Risks of Dynamic Manufacturing Networks through Cognitive Mapping

Part 17: Risk Analysis

Evaluation of the effect of complementary pollination on Actinidia deliciosa 'Hayward' in northwest Portugal

The objective of this research was to study the effect of complementary pollination on kiwifruit production and quality. For 3 years, complementary application of wet or dry pollen have been done at different stages of flower opening on vines in the Portuguese regions of Entre-Douro e Minho and Beira Litoral. Commercial production data were collected and fruit quality attributes were measured at harvest. Complementary pollination did not affect fruit soluble solids content or firmness in any year, and was beneficial for fruit size and commercial production in the third year only, showing that it is important in some conditions, when natural pollination is inadequate.

RISKS TO FOOD AVAILABILITY AND ACCESS FROM CLIMATE POLICIES: AN INTEGRATED ASSESSMENT OF REGIONAL FOOD AVAILABILITY AND ACCESS WITH ALTERNATIVE CLIMATE MITIGATION STRATEGIES TO 2050

Although mitigating GHG emissions is necessary to reduce the overall negative climate change impacts on crop yields and agricultural production, certain mitigation measures may generate unintended consequences to food availability and access due to land use competition and economic burden of mitigation. Prior studies have examined the co-impacts on food availability and global producer prices caused by alternative climate policies. More recent studies have looked at the reduction in total caloric intake driven by both changing income and changing food prices under one specific climate policy. However, due to inelastic calorie demand, consumers’ well-being are likely further reduced by increased food expenditures. Built upon existing literature, my dissertation explores how alternative climate policy designs might adversely affect both caloric intake and staple food budget share to 2050, by using the Global Change Assessment Model (GCAM) and a post-estimated metric of food availability and access (FAA). My dissertation first develop a set of new metrics and methods to explore new perspectives of food availability and access under new conditions. The FAA metric consists of two components, the fraction of GDP per capita spent on five categories of staple food and total caloric intake relative to a reference level. By testing the metric against alternate expectations of the future, it shows consistent results with previous studies that economic growth dominates the improvement of FAA. As we increase our ambition to achieve stringent climate targets, two policy conditions tend to have large impacts on FAA driven by competing land use and increasing food prices. Strict conservation policies leave the competition between bioenergy and agriculture production on existing commercial land, while pricing terrestrial carbon encourages large-scale afforestation. To avoid unintended outcomes to food availability and access for the poor, pricing land emissions in frontier forests has the advantage of selecting more productive land for agricultural activities compared to the full conservation approach, but the land carbon price should not be linked to the price of energy system emissions. These results are highly relevant to effective policy-making to reduce land use change emissions, such as the Reduced Emissions from Deforestation and Forest Degradation (REDD).

The Westerly Index as complementary indicator of the North Atlantic oscillation in explaining drought variability across Europe

This paper analyses the influence of different atmospheric circulation indices on the multi-scalar drought variability across Europe by using the Standardized Precipitation Evapotranspiration Index (SPEI). The monthly circulation indices used in this study include the North Atlantic oscillation (NAO), the East Atlantic (EA), the Scandinavian (SCAN) and the East Atlantic-Western Russia (EA-WR) patterns, as well as the recently published Westerly Index (WI), defined as the persistence of westerly winds over the eastern north Atlantic region. The results indicate that European drought variability is better explained by the station-based NAO index and the WI than by any other combination of circulation indices. In northern and central Europe the variability of drought severity for different seasons and time-scales is strongly associated with the WI. On the contrary, the influence of the NAO on southern Europe droughts is stronger than that exerted by the WI. The correlation patterns of the NAO and WI with the SPEI show a spatial complementarity in shaping drought variability across Europe. Lagged correlations of the NAO and WI with the SPEI also indicate enough skill of both indices to anticipate drought severity several months in advance. As long as instrumental series of the NAO and WI are available, their combined use would allow inferring European drought variability for the last two centuries and improve the calibration and interpretation of paleoclimatic proxies associated with drought.

Evaluation of the antioxidant activity and antitumor activity of marine invertebrates extracts

Dissertação de Mestrado, Biologia Marinha, Faculdade de Ciências e Tecnologias, Universidade do Algarve, 2014

Evaluation of the effect of complementary pollination on Actinidia deliciosa 'Hayward' in northwest Portugal

The objective of this research was to study the effect of complementary pollination on kiwifruit production and quality. For 3 years, complementary application of wet or dry pollen have been done at different stages of flower opening on vines in the Portuguese regions of Entre-Douro e Minho and Beira Litoral. Commercial production data were collected and fruit quality attributes were measured at harvest. Complementary pollination did not affect fruit soluble solids content or firmness in any year, and was beneficial for fruit size and commercial production in the third year only, showing that it is important in some conditions, when natural pollination is inadequate.

Assessment of the Occurrence and Potential Risks of Pharmaceuticals and their Metabolites in Fish and Water Using Liquid Chromatography Mass Spectrometry

A comprehensive method for the analysis of 11 target pharmaceuticals representing multiple therapeutic classes was developed for biological tissues (fish) and water. Water samples were extracted using solid phase extraction (SPE), while fish tissue homogenates were extracted using accelerated solvent extraction (ASE) followed by mixed-mode cation exchange SPE cleanup and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Among the 11 target pharmaceuticals analyzed, trimethoprim, caffeine, sulfamethoxazole, diphenhydramine, diltiazem, carbamazepine, erythromycin and fluoxetine were consistently detected in reclaimed water. On the other hand, caffeine, diphenhydramine and carbamazepine were consistently detected in fish and surface water samples. In order to understand the uptake and depuration of pharmaceuticals as well as bioconcentration factors (BCFs) under the worst-case conditions, mosquito fish were exposed to reclaimed water under static-renewal for 7 days, followed by a 14-day depuration phase in clean water. Characterization of the exposure media revealed the presence of 26 pharmaceuticals while 5 pharmaceuticals including caffeine, diphenhydramine, diltiazem, carbamazepine, and ibuprofen were present in the organisms as early as 5 h from the start of the exposure. Liquid chromatography ultra-high resolution Orbitrap mass spectrometry was explored as a tool to identify and quantify phase II pharmaceutical metabolites in reclaimed water. The resulting data confirmed the presence of acetyl-sulfamethoxazole and sulfamethoxazole glucuronide in reclaimed water. To my knowledge, this is the first known report of sulfamethoxazole glucuronide surviving intact through wastewater treatment plants and occurring in environmental water samples. Finally, five bioaccumulative pharmaceuticals including caffeine, carbamazepine, diltiazem, diphenhydramine and ibuprofen detected in reclaimed water were investigated regarding the acute and chronic risks to aquatic organisms. The results indicated a low potential risk of carbamazepine even under the worst case exposure scenario. Given the dilution factors that affect environmental releases, the risk of exposure to carbamazepine will be even more reduced.

Assessment of the Occurrence and Potential Risks of Antibiotics and their Metabolites in South Florida Waters Using Liquid Chromatography Tandem Mass Spectrometry

An automated on-line SPE-LC-MS/MS method was developed for the quantitation of multiple classes of antibiotics in environmental waters. High sensitivity in the low ng/L range was accomplished by using large volume injections with 10-mL of sample. Positive confirmation of analytes was achieved using two selected reaction monitoring (SRM) transitions per antibiotic and quantitation was performed using an internal standard approach. Samples were extracted using online solid phase extraction, then using column switching technique; extracted samples were immediately passed through liquid chromatography and analyzed by tandem mass spectrometry. The total run time per each sample was 20 min. The statistically calculated method detection limits for various environmental samples were between 1.2 and 63 ng/L. Furthermore, the method was validated in terms of precision, accuracy and linearity. The developed analytical methodology was used to measure the occurrence of antibiotics in reclaimed waters (n=56), surface waters (n=53), ground waters (n=8) and drinking waters (n=54) collected from different parts of South Florida. In reclaimed waters, the most frequently detected antibiotics were nalidixic acid, erythromycin, clarithromycin, azithromycin trimethoprim, sulfamethoxazole and ofloxacin (19.3-604.9 ng/L). Detection of antibiotics in reclaimed waters indicates that they can’t be completely removed by conventional wastewater treatment process. Furthermore, the average mass loads of antibiotics released into the local environment through reclaimed water were estimated as 0.248 Kg/day. Among the surface waters samples, Miami River (reaching up to 580 ng/L) and Black Creek canal (up to 124 ng/L) showed highest concentrations of antibiotics. No traces of antibiotics were found in ground waters. On the other hand, erythromycin (monitored as anhydro erythromycin) was detected in 82% of the drinking water samples (n.d-66 ng/L). The developed approach is suitable for both research and monitoring applications. Major metabolites of antibiotics in reclaimed wates were identified and quantified using high resolution benchtop Q-Exactive orbitrap mass spectrometer. A phase I metabolite of erythromycin was tentatively identified in full scan based on accurate mass measurement. Using extracted ion chromatogram (XIC), high resolution data-dependent MS/MS spectra and metabolic profiling software the metabolite was identified as desmethyl anhydro erythromycin with molecular formula C36H63NO12 and m/z 702.4423. The molar concentration of the metabolite to erythromycin was in the order of 13 %. To my knowledge, this is the first known report on this metabolite in reclaimed water. Another compound acetyl-sulfamethoxazole, a phase II metabolite of sulfamethoxazole was also identified in reclaimed water and mole fraction of the metabolite represent 36 %, of the cumulative sulfamethoxazole concentration. The results were illustrating the importance to include metabolites also in the routine analysis to obtain a mass balance for better understanding of the occurrence, fate and distribution of antibiotics in the environment. Finally, all the antibiotics detected in reclaimed and surface waters were investigated to assess the potential risk to the aquatic organisms. The surface water antibiotic concentrations that represented the real time exposure conditions revealed that the macrolide antibiotics, erythromycin, clarithromycin and tylosin along with quinolone antibiotic, ciprofloxacin were suspected to induce high toxicity to aquatic biota. Preliminary results showing that, among the antibiotic groups tested, macrolides posed the highest ecological threat, and therefore, they may need to be further evaluated with, long-term exposure studies considering bioaccumulation factors and more number of species selected. Overall, the occurrence of antibiotics in aquatic environment is posing an ecological health concern.