Tractado de republica co[n] otras Hystorias y antiguedades ...

Copia digital : Junta de Comunidades de Castilla-La Mancha, 2010Pie de imp. consta en colofónSign.: a-d\p6\s, e\p8\sLetra gót

Codes of best practice in competitive markets for managers

We study firms' corporate governance in environments where possibly heterogeneous shareholders compete for possibly heterogeneous managers. A firm, formed by a shareholder and a manager, can sign either an incentive contract or a contract including a Code of Best Practice. A Code allows for a better manager's control but makes manager's decisions hard to react when market conditions change. It tends to be adopted in markets with low volatility and in low-competitive environments. The firms with the best projects tend to adopt the Code when managers are not too heterogeneous while the best managers tend to be hired through incentive contracts when the projects are similar. Although the matching between shareholders and managers is often positively assortative, the shareholders with the best projects might be willing to renounce to hire the best managers, signing contracts including Codes with lower-ability managers

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair

The aim of this study was to evaluate injectable, in situ cross-linkable elastin-like recombinamers (ELRs) for osteochondral repair. Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells (rMSCs) were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits. Thus, cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4 months for histological and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality and the new matrix in the defects. Although both approaches helped cartilage regeneration, the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration, whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage. In conclusion, the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesisThis project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 642687. The authors are grateful for the funding from the European Commission (NMP-2014-646075), the Spanish Government (PCIN-2015-010, MAT2015-68901-R, MAT2016-78903-R, MAT2016-79435-R), Junta de Castilla y León (VA015U16) and Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León. The authors also wish to thank Maria Victoria Saez Velasco for her important contribution to cell culture experimentsS

Sharp increase of Saharan dust intrusions over the Western Mediterranean and Euro-Atlantic region in winters 2020–2022 and associated atmospheric circulation [Discussion paper]

During the winters of the 2020–2022 period, several intense North African dust intrusions affected Europe. Some of them displayed a duration never recorded before. They were referred to as exceptional by several international operational and research institutions considering that wintertime is the season with minimum dust activity in the Mediterranean and Europe. These anomalous winter events with origin in North Africa largely affected western Mediterranean. The main objective of the present work is to analyse the atmospheric drivers (synoptic and large-scale environments) of wintertime (from January to March) dust events over the region covering North Africa, the Western Mediterranean and the Euro-Atlantic during the period 2003–2022. Overall, our results indicate large interannual variability over the study period. A dust catalogue of dust events identified by aerosols retrievals from satellite and aerosol reanalysis products shows a very irregular record and large differences between winter months. The analyses demonstrate a positive anomaly in dust concentration and maximum altitude during the dust events of 2020–2022 in comparison with those of previous years (2003–2019). Winter dust events over western Mediterranean are associated with enhanced blocking activity over the Euro-Atlantic sector, which favours the obstruction of the westerlies and the occurrence of cut-off lows at subtropical latitudes. However, these high-pressure systems can exhibit a large variety of configurations, including meridional dipole blocking patterns with poleward shifted jets or Mediterranean subtropical ridges with an intensified mid-latitude jet. The former was more frequent during the reference 2003–2019 period, whereas the latter was relatively common during the anomalous 2020–2022 period

Recensiones

Óscar Alzaga Villaamil. La conquista de la transición (1960-1978). Memorias documentadas (María Garrote de Marcos) Artemi Rallo Lombarte. Investiduras fallidas y Constitución ignota (Nieves Alonso García) Juan Francisco Sánchez Barrilao. Pluralismo ordinamental y Derecho constitucional: El Derecho como relaciones entre ordenamientos jurídicos (Patricia García Majado) María Salvador Martínez. Partidos políticos. El estatuto constitucional en los partidos y su desarrollo legal (Eva Sáenz Royo) María Garrote De Marcos. El sistema electoral español: memoria, balance y cambio (Carlos Fernández Esquer) María Isabel González Pascual. La salvaguarda de la autonomía política ante las crisis (Andrés Dueñas Castrillo) Ángel Sánchez Navarro y Rosa Fernández Riveira (Dirs.). Reflexiones para una democracia de calidad en una era tecnológica y Jordi Barrat i Esteve y Miguel Pérez Moneo (Eds.). La digitalización de los partidos políticos y el uso del voto electrónico (José Luis Mateos Crespo

Activation of LXR nuclear receptors impairs the anti-inflammatory gene and functional profile of M-CSF-dependent human monocyte-derived macrophages

13 p.-7 fig.Liver X Receptors (LXR) control cholesterol metabolism and exert anti-inflammatory actions but their contribution to human macrophage polarization remains unclear. The LXR pathway is enriched in pro-inflammatory macrophages from rheumatoid arthritis as well as in tumors-associated macrophages from human tumors. We now report that LXR activation inhibits the anti-inflammatory gene and functional profile of M-CSF-dependent human macrophages, and prompts the acquisition of a pro-inflammatory gene signature, with both effects being blocked by an LXR inverse agonist. Mechanistically, the LXR-stimulated macrophage polarization shift correlates with diminished expression of MAFB and MAF, which govern the macrophage anti-inflammatory profile, and with enhanced release of activin A. Indeed, LXR activation impaired macrophage polarization in response to tumor-derived ascitic fluids, as well as the expression of MAF- and MAFB-dependent genes. Our results demonstrate that LXR activation limits the anti-inflammatory human macrophage polarization and prompts the acquisition of an inflammatory transcriptional and functional profile.This work was supported by grants from Ministerio de Ciencia, Investigación y Universidades (SAF2017-83785-R to MV and ALC), Ministerio de Ciencia, Innovación y Universidades y Fondo Europeo de Desarrollo Regional (FEDER) (SAF2017-90604-REDT and PID2019-104284RB-I00/AEI/10.13039/501100011033 to AC), Fundación La Marató/TV3 (Grant 201619.31 to ALC), Instituto de Salud Carlos III (Grant PI20/00316 to AP-K), and Red de Investigación en Enfermedades Reumáticas (RIER, RD16/0012/0007) from Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund “A way to achieve Europe” (ERDF) to AP-K and ALC. This work was also supported in part by a grant from the Dutch Society for Clinical Chemistry (NVKC) to IM and R. de Jonge. AGA was funded by FPU predoctoral fellowship (FPU16/02756) from Ministerio de Universidades.Peer reviewe

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression

Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. Materials and methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the HΨ Patients with a lower H&Y stage may be more affected if they have a greater NMS burden

Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

COPPADIS Study Group.[Background and objective] The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD).[Patients and Methods] PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%.[Results] In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2.[Conclusions] In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.Fundación Curemos el Parkinson (www.curemoselparkinson.org).Peer reviewe

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

COPPADIS Study Group.[Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients.[Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems.[Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments.[Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.Peer reviewe