A COMPARISON OF SPATIAL PREDICTION METHODS USING INTENSE SPATIALLY-ACQUIRED WATER QUALITY DATA

Water quality information obtained through intensive spatial sampling using automated devices provides opportunities to monitor and forecast the spatial distribution of nutrients and phytoplankton concentrations, and help establish water circulation patterns in estuarine and coastal waters. To be cost effective, efficient sampling designs and estimation methodologies must first be developed. As a starting basis, we applied an original transect sampling design that was used to estimate the spatial distribution of chlorophyll a, salinity, and temperature in the Cienaga Grande de Santa Marta, a coastal lagoon in Colombia. We superimposed the transects over satellite images of the lagoon obtained in the period 1993-2001 to evaluate the efficiency and accuracy of using such transects to estimate the distribution of water quality variables. The satellite images were taken in 1993 (SPOT-3), 1995 (Landsat-6), and 1999 (Landsat-6), and water reflectance values were used as a “proxy” for the water quality variables. Spatial prediction using kriging and thin-plate smoothing splines were used to predict reflectance for a grid network of points taken from the images, and predictions were compared with observed values to compare methods and transect routes. Rapid changes in reflectance in short distances (for example , caused by phytoplankton blooms), complicated the analysis, and neither method proved superior over all transect routes and images, although the kriging predictor remained relatively consistent in performance over the various selected sampling routes

Soluble CD137 as a dynamic biomarker to monitor agonist CD137 immunotherapies

Background On the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved chimeric antigen receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and costimulation of T cells will facilitate clinical development of CD137 agonists in the clinic. Methods We used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored on treatment with agonist anti-CD137 monoclonal antibodies (mAbs). Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 mAb (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISA and Luminex. Flow cytometry was used to monitor CD137 surface expression. Results CD137 costimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 costimulation inside subcutaneously implanted Matrigel plugs. The CD137 signaling domain-containing CAR T cells readily released sCD137 and acquired CD137 surface expression on antigen recognition. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137. Conclusion sCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic costimulatory activity elicited by agonist CD137-targeted agents

A Spanish version for the new ERA-EDTA coding system for primary renal disease

Background: The European Renal Association and the European Dialysis and Transplant Association (ERA-EDTA) have issued an English-language new coding system for primary kidney disease (PKD) aimed at solving the problems that were identified in the list of "Primary renal diagnoses" that has been in use for over 40 years. Purpose: In the context of Registro Español de Enfermos Renales (Spanish Registry of Renal Patients, REER]), the need for a translation and adaptation of terms, definitions and notes for the new ERA-EDTA codes was perceived in order to help those who have Spanish as their working language when using such codes. Methods: Bilingual nephrologists contributed a professional translation and were involved in a terminological adaptation process, which included a number of phases to contrast translation outputs. Codes, paragraphs, definitions and diagnostic criteria were reviewed and agreements and disagreements aroused for each term were labelled. Finally, the version that was accepted by a majority of reviewers was agreed. Results: A wide agreement was reached in the first review phase, with only 5 points of discrepancy remaining, which were agreed on in the final phase. Conclusions: Translation and adaptation into Spanish represent an improvement that will help to introduce and use the new coding system for PKD, as it can help reducing the time devoted to coding and also the period of adaptation of health workers to the new codes

A Spanish version for the new ERA-EDTA coding system for primary renal disease

Background: The European Renal Association and the European Dialysis and Transplant Association (ERA-EDTA) have issued an English-language new coding system for primary kidney disease (PKD) aimed at solving the problems that were identified in the list of "Primary renal diagnoses" that has been in use for over 40 years. Purpose: In the context of Registro Español de Enfermos Renales (Spanish Registry of Renal Patients, REER]), the need for a translation and adaptation of terms, definitions and notes for the new ERA-EDTA codes was perceived in order to help those who have Spanish as their working language when using such codes. Methods: Bilingual nephrologists contributed a professional translation and were involved in a terminological adaptation process, which included a number of phases to contrast translation outputs. Codes, paragraphs, definitions and diagnostic criteria were reviewed and agreements and disagreements aroused for each term were labelled. Finally, the version that was accepted by a majority of reviewers was agreed. Results: A wide agreement was reached in the first review phase, with only 5 points of discrepancy remaining, which were agreed on in the final phase. Conclusions: Translation and adaptation into Spanish represent an improvement that will help to introduce and use the new coding system for PKD, as it can help reducing the time devoted to coding and also the period of adaptation of health workers to the new codes

A Model of Continuous Improvement Programme Management

The aim of this study is to identify key management decisions that enable the sustainment of a continuous improvement (CI) initiative. To accomplish this aim, we examine the procedures and practices used by two manufacturing companies for the management of their CI initiatives; one that is successfully sustaining the effectiveness of its CI initiative and another failing to do the same. This research makes two contributions to the conceptual understanding of CI programme management. First, we identify five CI programme management factors that enable the sustainment of a CI initiative. Second, the five factors are incorporated into a new CI programme management model. The model details a ‘bottom-up’ procedure for the generation of manufacturing performance improvement ideas and the management of their implementation

APC/C-Mediated Degradation of dsRNA-Binding Protein 4 (DRB4) Involved in RNA Silencing

Background: Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells. However, its role in post-mitotic cells remains elusive and only a few substrates have been characterized. Methodology/Principal Findings: In order to identify novel APC/C substrates, we performed a yeast two-hybrid screen using as the bait Arabidopsis APC10/DOC1, one core subunit of the APC/C, which is required for substrate recruitment. This screen identified DRB4, a double-stranded RNA binding protein involved in the biogenesis of different classes of small RNA (sRNA). This protein interaction was further confirmed in vitro and in plant cells. Moreover, APC10 interacts with DRB4 through the second dsRNA binding motif (dsRBD2) of DRB4, which is also required for its homodimerization and binding to its Dicer partner DCL4. We further showed that DRB4 protein accumulates when the proteasome is inactivated and, most importantly, we found that DRB4 stability depends on APC/C activity. Hence, depletion of Arabidopsis APC/C activity by RNAi leads to a strong accumulation of endogenous DRB4, far beyond its normal level of accumulation. However, we could not detect any defects in sRNA production in lines where DRB4 was overexpressed

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

El enano con pies de barro: la protección internacional de los defensores de derechos humanos en estos tiempos. El caso de Colombia

La relación entre el discurso relativo a los derechos humanos y la realidad de la protección a los mismos siempre ha sido objeto de análisis, y hay una abundante literatura sobre ella. Pero se debe volver sobre tales reflexiones una vez más: ¿qué podemos decir de dicha relación entre discurso y protección real, en unos momentos en que los discursos se están viendo copados por la atención prioritaria de muchos gobiernos hacia el fenómeno que definen como terrorismo internacional? En este artículo propondremos un modelo de espacio de actuación, que puede servir para relacionar el discurso sobre derechos humanos y las actuaciones de protección hacia los mismos. Veremos cómo las tendencias actuales influyen en esta relación y lo interpretaremos aplicándolo al caso de Colombia