Forgotten giants: Robust climate signal in pollarded trees.

Tree ring records are among the most valuable resources to create high-resolution climate reconstructions. Most climate reconstructions are based on old trees growing in inaccessible mountainous areas with low human activity. Therefore, reconstruction of climate conditions in lowlands is usually based on data from distant mountains. Albeit old trees can be common in humanized areas, they are not used for climate reconstructions. Pollarding was a common traditional management in Europe that enabled trees to maintain great vitality for periods exceeding the longevity of unmanaged trees. We evaluate the potential of pollarded deciduous oaks to record past climate signal. We sampled four pollarded woodlands in Central Spain under continental Mediterranean climate. We hypothesized that pollarded trees have a strong response to water availability during current period without pollarding management, but also in the period under traditional management if pruning was asynchronous among trees. Moreover, we hypothesized that if climate is a regional driver of oak secondary growth, chronologies from different woodlands will be correlated. Pollard oaks age exceeded 500 years with a strong response to Standardized Precipitation-Evapotranspiration Index (SPEI) from 9 to 11 months. Climate signal was exceptionally high in three of the sites (r2 = 0.443-0.655) during low management period (1962-2022). The largest fraction of this climate signal (≈70 %) could be retrieved during the traditional management period (1902-1961) in the three sites where pollarding was asynchronous. Chronologies were significantly correlated since the 19th century for all the studied period, highlighting a shared climate forcing. We identified critical points to optimize pollard tree sampling schema. Our results show the enormous potential of pollarded woodlands to reconstruct hydroclimate conditions in the Mediterranean with a fine spatial grain. Studying pollarded trees is an urgent task, since the temporal window to retrieve the valuable information in pollarded trees is closing as these giants collapse and their wood rots.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Paediatric nuclear medicine practice: an international survey by the IAEA.

PURPOSE: The International Atomic Energy Agency (IAEA) decided to initiate a survey to evaluate the current status of the practice of paediatric nuclear medicine worldwide, with the focus mainly on low and middle-income countries specifically in Latin America, Eastern Europe, Africa and Asia. This investigation sought to determine if the practice in paediatric nuclear medicine in these countries differed from that indicated by the survey of the Nuclear Medicine Global Initiative (NMGI) and if nuclear medicine practitioners were following established paediatric nuclear medicine guidelines. METHODS: A total of 133 institutes took part in the survey from 62 different IAEA member states within Africa (29), Asia (39), Europe (29) and Latin America (36). The four most frequent conventional (single-photon) nuclear medicine procedures were 99mTc labelled MDP, DSMA, MAG3 and pertechnetate thyroid scans. In addition, 46 centres provided data on FDG PET/CT, including exposure data for the CT component. Nearly half of the sites (48%) perform less than 200 paediatric nuclear medicine studies per year, while 11% perform more than 1000 such studies per year. RESULTS: Administered activities largely exceeded the recommendations for most of the sites for DMSA, MAG3 and pertechnetate, while compliance with international standards was somehow better for MDP studies. For FDG PET, the results were more uniform than for conventional nuclear medicine procedures. However, the use of CT in PET/CT for paediatric nuclear medicine revealed a high variability and, in some cases, high, dose-length product (DLP) values. This observation indicates that further attention is warranted for optimizing clinical practice in FDG PET/CT. CONCLUSIONS: Overall, in most parts of the world, efforts have been undertaken to comply either with the EANM dosage card or with the North American Consensus Guidelines. However, variability in the practice of paediatric nuclear medicine still exists. The results of this survey provide valuable recommendations for a path towards global standardization of determining the amount of activity to be administered to children undergoing nuclear medicine procedures.

Historical evolution of the diseases caused by non-pigmented rapidly growing mycobacteria in a University Hospital.

OBJECTIVE: Non-pigmented rapidly growing mycobacteria (NPRGM) are a group of organisms of increasing interest due to the growing number of potential patients and the difficulties for a proper treatment in many of them. However, the evolution of these diseases in a long period of time and its evolutionary changes has been described only in a scanty number of reports. METHODS: We performed a retrospective study between January 1st 2004 and December 31st 2017 in order to evaluate the clinical significance and types of diseases caused by NPRGM. Patients with isolates of NPRGM during this period were selected for the study, and clinical charts were reviewed using a predefined protocol. RESULTS: During this period we identified 59 patients (76 clinical samples) with isolates of NPRGM, with 12 cases of clinical disease and one patient with doubtful significance (including 6 respiratory tract infections, 2 catheter infections, 1 skin and soft tissue infection, 1 disseminated infection, 1 conjunctivitis, 1 prosthetic joint infection and 1 mastitis). Fifty percent of M. chelonae isolates, 37.5% of M. abscessus isolates and 23.33% of M. fortuitum isolates were clinically significant. None of the isolates of other species were significant. CONCLUSIONS: Most isolates in respiratory samples were contaminants/colonizations. M. abscessus was the main etiological agent in respiratory syndromes, whereas M. chelonae and M. fortuitum were more frequently associated with other infections, especially clinical devices and skin and soft tissue infections.

Finger and forehead PPG signal comparison for respiratory rate estimation.

OBJECTIVE: An evaluation of the location of the photoplethysmogram (PPG) sensor for respiratory rate estimation is performed. APPROACH: Finger PPG, forehead PPG, and respiratory signal were simultaneously recorded from 35 subjects while breathing spontaneously, and during controlled respiration experiments at a constant rate from 0.1 Hz to 0.6 Hz, in 0.1 Hz steps. Four PPG-derived respiratory (PDR) signals were extracted from each one of the recorded PPG signals: pulse rate variability (PRV), pulse width variability, pulse amplitude variability and the respiratory-induced intensity variability (RIIV). Respiratory rate was estimated from each one of the four PDR signals for both PPG sensor locations. In addition, different combinations of PDR signals, power distribution of the respiratory frequency range and differences of the morphological parameters extracted from both PPG signals have been analysed. MAIN RESULTS: Results show better performance in terms of successful estimation and relative error when: (i) PPG signal is recorded in the finger; (ii) the respiratory rate is less than 0.4 Hz; (iii) RIIV signal is not considered. Furthermore, lower spectral power around the respiratory rate in the PDR signals recorded from the forehead was observed. SIGNIFICANCE: These results suggest that respiratory rate estimation is better at lower rates (0.4 Hz and below) and that the finger is better than the forehead to estimate respiratory rate.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

BACKGROUND: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. METHODS: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. RESULTS: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. CONCLUSION: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

Indirect comparison for Anti-TNF drugs in moderate to severe ulcerative colitis.

OBJECTIVE: To compare the relative efficacy of infliximab, adalimumab and golimumab through adjusted indirect treatment comparisons (ITCs). METHODS: An exhaustive search was performed until October 2013. Databases consulted were MEDLINE, EMBASE, the Cochrane Library, the Centre for Reviews and Dissemination and the Web of Science. Randomized control trials (RCTs) comparing the efficacy of infliximab, adalimumab or golimumab versus placebo, in terms of clinical remission, clinical response and mucosal healing, were included. In the case that more than one RCT fulfilled the inclusion criteria for the same drug, a metanalysis was undertaken using a fixed effects model. ITCs were carried out using the method proposed by Bucher et al. RESULTS: 6 RCTs published in 5 papers were included: 2 for infliximab (ACT 1 and ACT 2), 2 for adalimumab (ULTRA 1 y ULTRA 2) and 2 for golimumab (PURSUIT-SC y PURSUIT-M).In these RTCs, each biological agent was superior in efficacy to placebo. The results of the adjusted ITC are the following. In relation to the clinical remission, in the induction and maintenance period, there are no statistically significant differences between the three anti-TNF drugs. In relation to the clinical response and mucosal healing, in the induction period, there are statistically significant differences between infliximab and adalimumab. CONCLUSION: In view of the results obtained, infliximab, adalimumab and golimumab appear to be similarly effective therapeutic alternatives. Therefore, other considerations such as safety, tolerance and cost-effectiveness should be taken into account in order to select the most appropriate treatment.

Objetivo: Comparar la eficacia relativa de infliximab, adalimumab y golimumab mediante comparaciones indirectas (CI) ajustadas. Métodos: Se realizó una búsqueda bibliográfica que abarcó hasta Octubre 2013. Las bases de datos consultadas fueron: MEDLINE, EMBASE, the Cochrane Library, the Centre for Reviews and Dissemination y the Web of Science. Se incluyeron ensayos clínicos aleatorizados (ECA) que compararan la eficacia de infliximab, adalimumab o golimumab frente a placebo en términos de remisión clínica, respuesta clínica y curación de la mucosa. En el caso de que se incluyera más de un ECA para un mismo fármaco se llevó a cabo un metanálisis utilizado el modelo de efectos fijos. Las CI se realizaron utilizando el método de Butcher et al. Resultados: Se incluyeron 6 ECA publicados en 5 artículos: 2 para infliximab (ACT 1 y ACT 2), 2 para adalimumab (ULTRA 1 y ULTRA 2) y 2 para golimumab (PURSUIT-SC y PURSUIT-M). Los tres agentes biológicos presentaron mayor eficacia que placebo. Los resultados de las CI fueron los siguientes: en relación a la remisión clínica, en el período de inducción y en el período de mantenimiento, no hubo diferencias estadísticamente significativas entre los tres fármacos anti-TNF. En relación a la respuesta clínica y a la curación de la mucosa, en el período de inducción hay diferencias estadísticamente significativas entre infliximab y adalimumab. Conclusiones: En base a los resultados obtenidos (eficacia similar), infliximab, adalimumab y golimumab parecen ser alternativas terapéuticas. Así, otras consideraciones como la seguridad, la tolerancia y el coste-efectividad deben considerarse a la hora de seleccionar el tratamiento más adecuado.

Factors related with the appropriateness of pharmacological treatment in polypathological patients.

OBJECTIVE: To evaluate the association between the number of pharmacological inappropriateness and possible factors related with it. METHODS: All polyphatological patients of the IMPACTO project in a tertiary hospital were included (July 2010-March 2012). The pharmacist performed the interventions based on a combined strategy that included the modified MAI and the STOPP-START criteria. A greater number of interventions indicated smaller treatment appropriateness. In the analysis of the strength of association between two continuous variables the Pearson correlation coefficient was used. Test of Student's t or Mann-Whitney comparisons of quantitative data between two groups were applied. Subsequently, a multivariate analysis was performed to study possible variables which explain the inappropriateness of the pharmacological treatment. RESULTS: 242 patients were included. 838 inappropriateness were detected (average per patient of 3±2). The appropriateness was associated with: number of diagnoses, medications, and categories of polypathology, Charlson Comorbidity Index, sex, and categories A1 and B2. When diagnosing collinearity in the multivariate model, we observed that there was collinearity between "Charlson Comorbidity Index" and "number of categories of polypathological patients", so it was decided to conduct two multivariate models variables, one each. The number of drugs, the number of diagnoses and the gender remained significant in both multivariate models. CONCLUSIONS: The appropriateness of pharmacological treatment decreases with increasing number of drugs and number of diagnoses, as well as female gender. However, both multi variate models explain a low percentage of variability in the number of inappropriateness.

Objetivo: evaluar la asociación entre el número de inadecuaciones farmacológicas y posibles factores relacionados con la misma. Métodos: : Se incluyeron todos los pacientes pluripatológicos del proyecto IMPACTO en un hospital de tercer nivel (Julio 2010-Marzo 2012). El farmacéutico realizó las intervenciones en base a una estrategia combinada que incluía el MAI modificado y los criterios STOPP-START. A mayor número de intervenciones menor adecuación del tratamiento. En los análisis de la fuerza de asociación entre dos variables continuas se utilizó el coeficiente de correlación de Pearson. Se aplicó el test de la t de Student o U de Mann-Whitney en comparaciones de datos cuantitativos entre dos grupos. Posteriormente, se realizó un análisis multivariante, para estudiar posibles variables que explicasen las inadecuaciones del tratamiento farmacológico. Resultados: Se incluyeron un total de 242 pacientes. Se detectaron un total de 838 inadecuaciones, siendo la media por paciente de 3±2. La adecuación del tratamiento farmacológico se asoció con el número de diagnósticos, el número de medicamentos, el número de categorías de paciente pluripatológico, el índice de comorbilidad de Charlson, el sexo y las categorías A1 y B2. Al realizar el diagnóstico de colinealidad, en el modelo multivariante, de las variables se observó que existía colinealidad entre las variables "índice de comorbilidad de Charlson" y "número de categorías de paciente pluripatológico", por lo que se decidió realizar dos modelos multivariantes, uno con cada una de ellas. Se mantuvieron significativos con el multivariante y para ambos modelos el número de medicamentos, el número de diagnósticos y el sexo. Conclusiones: La adecuación del tratamiento farmacológico disminuyó al aumentar el número de medicamentos y el número de diagnósticos, así como en mujeres. No obstante, ambos modelos multivariantes, explicaron un porcentaje de variabilidad del número de inadecuaciones leve.

Cross time-frequency analysis for combining information of several sources: application to estimation of spontaneous respiratory rate from photoplethysmography.

A methodology that combines information from several nonstationary biological signals is presented. This methodology is based on time-frequency coherence, that quantifies the similarity of two signals in the time-frequency domain. A cross time-frequency analysis method, based on quadratic time-frequency distribution, has been used for combining information of several nonstationary biomedical signals. In order to evaluate this methodology, the respiratory rate from the photoplethysmographic (PPG) signal is estimated. The respiration provokes simultaneous changes in the pulse interval, amplitude, and width of the PPG signal. This suggests that the combination of information from these sources will improve the accuracy of the estimation of the respiratory rate. Another target of this paper is to implement an algorithm which provides a robust estimation. Therefore, respiratory rate was estimated only in those intervals where the features extracted from the PPG signals are linearly coupled. In 38 spontaneous breathing subjects, among which 7 were characterized by a respiratory rate lower than 0.15 Hz, this methodology provided accurate estimates, with the median error {0.00; 0.98} mHz ({0.00; 0.31}%) and the interquartile range error {4.88; 6.59} mHz ({1.60; 1.92}%). The estimation error of the presented methodology was largely lower than the estimation error obtained without combining different PPG features related to respiration.

Reliability of a questionnaire for pharmacological treatment appropriateness in patients with multiple chronic conditions.

BACKGROUND: The original Medication Appropriateness Index was validated for elderly and polymedicated patients, both in hospital and outpatient contexts. However, no studies have applied this questionnaire in patients with multiple chronic conditions. The objective of this study is to assess the reliability of a modified Medication Appropriateness Index questionnaire in a population of patients with multiple chronic conditions. METHODS: We selected patients with multiple chronic conditions who were included in an integrated care project conducted at the Hospital Universitario Virgen del Rocío. To determine inter-observer reliability, each professional (internist or hospital pharmacy specialist) applied the questionnaire under the same conditions and with the same resources. To determine intra-observer reliability, each physician applied the tool at baseline and two months later. We measured inter- and intra-observer reliability using the kappa coefficient. The proportion of overall agreement was also determined. RESULTS: We obtained a weak overall kappa (k=0.38) for inter-observer reliability and moderate (k=0.52) and very good (k=0.84) values for intra-observer reliability of the internist and specialist in hospital pharmacy, respectively. The proportion of overall agreement is very high in all three situations: 96%, 98%, and 99%, respectively. CONCLUSIONS: Despite its limitations, the Medication Appropriateness Index questionnaire modified by our group can be used, as a reliable method, to assess the appropriateness of pharmacotherapy in patients with multiple chronic conditions.

Treatment of agro-industrial wastewater using microalgae-bacteria consortium combined with anaerobic digestion of the produced biomass.

Two combined processes were studied in order to produce second generation biofuels: microalgae biomass production and its further use to produce biogas. Two 5 L photobioreactors for treating wastewater from a potato processing industry (from now on RPP) and from a treated liquid fraction of pig manure (from now on RTE) were inoculated with Chlorella sorokiniana and aerobic bacteria at 24±2.7 °C and 6000 lux for 12 h per day of light supply. The maximum biomass growth was obtained for RTE wastewater, with 26.30 mg dry weight L(-1) d(-1). Regarding macromolecular composition of collected biomass, lipid concentration reached 30.20% in RPP and 4.30% in RTE. Anaerobic digestion results showed that methane yield was highly influenced by substrate/inoculum ratio and by lipids concentration of the biomass, with a maximum methane yield of 518 mL CH4 g COD(-1)added using biomass with a lipid content of 30% and a substrate/inoculum ratio of 0.5.

[Health care models for patients with multiple chronic conditions and the role of the hospital pharmacy/the hospital pharmacist]. / Modelos de atención al paciente pluripatológico y el papel de la farmacia hospitalaria.

INTRODUCTION: Managing care for patients with chronic conditions currently represents one of the greatest challenges to health care systems. As a subgroup of these patients, those with multiple chronic conditions are at greater risk for death or disability, and they consume more resources. They are characterized by the coexistence of two or more chronic illnesses lasting a year or longer which require ongoing medical attention and/or interfere with their daily activities. For these polypathological patients pharmaceutical care would be of special benefit, thus, their needs should be a priority objective for hospital pharmacy. OBJECTIVE: To increase awareness of this type of patients and the characteristics of the principal approaches and health care models proposed to improve chronic disease management, as well as to emphasize the urgency for hospital pharmacists to join these models, and to present various activities that pharmacists might carry out as an integral part of these approaches. RESULTS: Numerous models exist internationally, including the Chronic Care Model and the Kaiser Permanente pyramid of risks. In our country a growing number of initiatives has culminated in the recent Seville Declaration. For the hospital pharmacy, caring for the chronically ill patient following a model that is multi-professional, cooperative, integral, and patient centered, is an enormous task. Pharmacy departments and the Spanish Society of Hospital Pharmacy should reorient their strategies for pharmaceutical care, training, and research. Of special interest are those activities designed to improve adherence, adequacy, and continuity in treatments, all the while emphasizing active patient participation.

Scale-dependent segregation of seeders and resprouters in cork oak (Quercus suber) forests.

Recent studies showed that disturbances and water availability determine the richness among plants with different post-fire strategies of Mediterranean-type ecosystems. The aim of this study was to determine whether or not the scale of analysis has an influence on the effects of these factors and, therefore, on the segregation of the dominant post-fire strategies, obligate seeders and obligate resprouters, and facultative species. We recorded all woody species and geographical features on 94 (75 m(2)) plots of cork oak woodlands in the southern Iberian Peninsula. For each regenerative type (resprouters, seeders and species with both traits--facultative species), we tested the relationship between the number of species and the predictors using a generalised linear mixed model. The fixed predictor considered at the large scale was altitude, and fixed predictors considered at the local scale were aspect (north/south) and disturbance (fire and clearing by heavy machinery; yes/no). The random predictor was the factor of site. When this factor did not have significant effect for some regenerative types, these relationships was tested using a generalised linear model. Resprouting species were most represented at lower altitudes and in undisturbed sites, while seeders were also at lower altitudes but mostly on south-facing slopes, especially south-facing disturbed sites. For facultative species, site is the most important variable. The proportion of seeders from the total species is not related to altitude, but it is related to disturbance and aspect. These results suggest that there is no segregation of the richness of seeders and resprouters at the large scale (altitudinal gradient). Differences appeared at the local scale (aspect and disturbance).

Kinetic study of ozonation of molasses fermentation wastewater.

A kinetic study of molasses wastewater ozonation was carried out in a stirred tank reactor to obtain the rate constants for the decolorization reaction and the regime through which ozone is absorbed. First, fundamental mass transfer parameters such as ozone solubility, volumetric mass transfer coefficients and ozone decomposition kinetics were determined from semi-batch experiments in organic-free solutions with an ionic composition similar that of industrial wastewater. The influence of operating variables such as the stirring rate and gas flow rate on the kinetic and mass transfer parameters was also studied. The application of film theory allows to establish that the reactions between ozone and colored compounds in wastewater take place in the fast and pseudo-first-order regime, within the liquid film. The decolorization rate constants were evaluated at pH 8.7 and 25 degrees C, varying from 0.6 x 10(7) to 3.8 x 10(7)L mol(-1)s(-1), depending on the stirring rate and the inlet gas flow.

Variables affecting efficiency of molasses fermentation wastewater ozonation.

The main operating variables affecting ozonation efficiencies of wastewater from beet molasses alcoholic fermentation have been studied. Semibatch experiments have been performed in order to analyze the influence of pH, bicarbonate ion, temperature and stirring rate on color and organic matter removals. The efficiencies were similar regardless of the pH, which indicates that direct reactions of ozone with wastewater organics were predominant to radical reactions. Gel permeation chromatography confirmed the reduction in the concentration of organics absorbing light at 475 nm after ozonation. The elimination of bicarbonate ion, strong inhibitor of hydroxyl radical reactions, yielded an improvement in both color and COD reduction efficiencies. Acidification for removing bicarbonate ions produced a shift of colored compounds to smaller molecular weights. The highest efficiencies were achieved at 40 degrees C. Color and COD reductions at 40 degrees C were about 90% and 37%, respectively. In no case, the percentage of TOC removed was higher than 10-15%. Stirring rate had a slightly positive effect during the first stage of the ozonation showing that mass transfer played a role only during the initial reaction phase when direct attack of ozone molecules to aromatic/olefinic structures of colored substances was the predominant pathway.

Chemical oxidation of wastewater from molasses fermentation with ozone.

Color removal from biologically pre-treated molasses wastewater by means of chemical oxidation with ozone has been investigated. Batch experiments have been performed in order to analyze the influence of ozone dosage and reaction time on color removal, molecular weight distribution and decolorization kinetics. Depending on the applied ozone dosage, color removal from 71% to 93% and COD reduction from 15% to 25% were reached after 30 min reaction time. TOC values remained constant throughout ozonation. Gel permeation chromatography corroborated that high molecular weight compounds, responsible for the brown color, were present in raw wastewater. UV spectral studies confirmed that these colored compounds were melanoidins. As a result of ozonation the concentration of chromophore groups decreased. Ozonation of synthetic melanoidin under the same experimental conditions provided similar color removal efficiencies. Pseudo-first order kinetics with respect to colored compounds were found.