Caos y complejidad en Ciencias de la Vida

En los últimos años, y siguiendo una larga tradición en que las Matemáticas y la Física han contribuido notablemente al desarrollo de las ciencias de la vida, ha habido un resurgir de esta contribución. En el presente artículo se presenta una visión panorámica acerca de algunas aplicaciones de la Dinámica No Lineal, la Teoría del Caos y la Física de los Sistemas Complejos en las Ciencias de la Vida, en particular las neurociencias y las redes de regulación genéticas. Todo ello muestra que estamos ante un impulso de naturaleza interdisciplinar, del que pueden esperarse resultados esperanzadore

Analysis of Chaos-Based Coded Modulations under Intersymbol Interference

Ministerio de Educación y CienciaMinisterio de Ciencia e InnovaciónMinisterio de IndustriaComunidad de Madri

Estrategias en internet a partir de un modelo de dinámica competitiva

The present paper studies the characteristics and strategies suggested by a model of web sites competition dynamics, based on the Lotka-Volterra competition equations. The model captures the well know winner-take-all characteristic that is caused by the strong positive feedback mechanisms linked to high competence. From the analysis, both quantitative and qualitatively, of the model a series of strategic recommendations are offered to reach success, that prove to be coherent with the trends observed in the Internet real market. Among the above mentioned recommendations, the strategy of coopetition is highlighted as the most suitable option for small sites in order to deal with the leaders of the Net, being this one of the most interesting and novel behaviors that arise from the above mentioned analysis. This alternative strategy to the competition is backed by the predictions offered by a model of competitive dynamics. Furthermore, a series of interesting strategies for start-ups sites or new comers to the market are suggested, like segmentation and affiliation programs between vertical portals.En el presente trabajo se estudia un modelo que describe las principales características del mercado de Internet y las dinámicas competitivas de los denominados sitios web. Este modelo, basado en las ecuaciones de Lotka-Volterra, analiza situaciones del tipo ‘el ganador se lleva todo’ manifestadas recurrentemente en mercados altamente competitivos. Con base en su tratamiento tanto cuantitativo como cualitativo se ofrecen una serie de recomendaciones estratégicas para mejorar resultados, por supuesto, coherentes con las tendencias observadas en la realidad de la Red. Dentro de estas recomendaciones destaca la estrategia de competición, que se propone como una opción viable para que los sitios pequeños puedan hacer frente a los grandes líderes de Internet; reforzada por su fundamento en consonancia con las predicciones propias de un modelo de dinámica competitiva. Junto a ello, también se formulan diversas estrategias para los sitios de nueva creación o recién llegados al mercado (los conocidos start-ups) como la de segmentación y los programas de filiación entre portales verticales

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of lifeThis project was partially supported by Fundación Española de Farmacia Hospitalaria “Convocatoria de ayudas de proyectos para grupos de trabajo de la SEFH 2021-2022”, Plan Galego de Saude Mental (SERGAS) and Axencia Galega Innovación (Grupos de Potencial Crecimiento IN607B2020/11). Bandín-Vilar E.: Mondelo-García C. and Fernández-Ferreiro A. are grateful to the Carlos III Health Institute for financing their personnel contracts: CM20/00135, JR20/00026 and JR18/00014S

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center

The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3-20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2-38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement

Pancreatic metastases from renal cell carcinoma. Postoperative outcome after surgical treatment in a Spanish multicenter study (PANMEKID)

Background: Renal Cell Carcinoma (RCC) occasionally spreads to the pancreas. The purpose of our study is to evaluate the short and long-term results of a multicenter series in order to determine the effect of surgical treatment on the prognosis of these patients. Methods: Multicenter retrospective study of patients undergoing surgery for RCC pancreatic metastases, from January 2010 to May 2020. Variables related to the primary tumor, demographics, clinical characteristics of metastasis, location in the pancreas, type of pancreatic resection performed and data on short and long-term evolution after pancreatic resection were collected. Results: The study included 116 patients. The mean time between nephrectomy and pancreatic metastases' resection was 87.35 months (ICR: 1.51-332.55). Distal pancreatectomy was the most performed technique employed (50 %). Postoperative morbidity was observed in 60.9 % of cases (Clavien-Dindo greater than IIIa in 14 %). The median follow-up time was 43 months (13-78). Overall survival (OS) rates at 1, 3, and 5 years were 96 %, 88 %, and 83 %, respectively. The disease-free survival (DFS) rate at 1, 3, and 5 years was 73 %, 49 %, and 35 %, respectively. Significant prognostic factors of relapse were a disease free interval of less than 10 years (2.05 [1.13-3.72], p 0.02) and a history of previous extrapancreatic metastasis (2.44 [1.22-4.86], p 0.01). Conclusions: Pancreatic resection if metastatic RCC is found in the pancreas is warranted to achieve higher overall survival and disease-free survival, even if extrapancreatic metastases were previously removed. The existence of intrapancreatic multifocal compromise does not always warrant the performance of a total pancreatectomy in order to improve survival

Estrategias en Internet a partir de un modelo de dinámica competitiva

En el presente trabajo se estudia un modelo que describe las principales características del mercado de Internet y las dinámicas competitivas de los denominados sitios web. Este modelo, basado en las ecuaciones de Lotka- Volterra, analiza situaciones del tipo "el ganador se lleva todo" manifestadas recurrentemente en mercados altamente competitivos. Con base en su tratamiento tanto cuantitativo como cualitativo se ofrecen una serie de recomendaciones estratégicas para mejorar resultados, por supuesto, coherentes con las tendencias observadas en la realidad de la Red. Dentro de estas recomendaciones destaca la estrategia de coopetición, que se propone como una opción viable para que los sitios pequeños puedan hacer frente a los grandes líderes de Internet; reforzada por su fundamento en consonancia con las predicciones propias de un modelo de dinámica competitiva. Junto a ello, también se formulan diversas estrategias para los sitios de nueva creación o recién llegados al mercado (los conocidos start-ups) como la de segmentación y los programas de filiación entre portales verticales

Natural Fluorite from Órgiva Deposit (Spain). A Study of Its Pozzolanic and Mechanical Properties

This work presents the results of the partial substitution of Portland cement (PC) by natural fluorite (NF) and calcined fluorite (CF) in mortars, at 10%, 25% and 40%. To meet these objectives, a sample of fluorite was initially studied by XRD, SEM and Raman Spectroscopy (RS). A chemical quality analysis (CQA) and a chemical pozzolanicity test (CPT) at 8 and 15 days were carried out in a second stage to establish the pozzolanic properties of the investigated sample. Finally, a mechanical compressive strength test (MCST) at 7, 28 and 90 days was carried out on specimens made up with PC/NF and PC/CF mixes, at a ratio of 10%, 25% and 40%. XRD, SEM and RS results indicated fluorite as the major mineralogical phase. The CPT and CQA showed an increase in the pozzolanicity of the samples from 8 to 15 days. The MCST showed an increase in compressive strength from 7 to 90 days for both PC/NF and PC/CF specimens. The results obtained establish that fluorite produces positive effects in the mortar and contributes to the gain of mechanical strength over time, being a suitable material for the manufacture of cements with pozzolanic addition with a reduction of CO2 emissions, and by reducing the energy costs of production

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice.

Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p  In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials

Incidence and clinical manifestations of giant cell arteritis in Spain: results of the ARTESER register

Objective This study aimed to estimate the incidence of giant cell arteritis (GCA) in Spain and to analyse its clinical manifestations, and distribution by age group, sex, geographical area and season.Methods We included all patients diagnosed with GCA between 1 June 2013 and 29 March 2019 at 26 hospitals of the National Health System. They had to be aged ≥50 years and have at least one positive results in an objective diagnostic test (biopsy or imaging techniques), meet 3/5 of the 1990 American College of Rheumatology classification criteria or have a clinical diagnosis based on the expert opinion of the physician in charge. We calculated incidence rate using Poisson regression and assessed the influence of age, sex, geographical area and season.Results We identified 1675 cases of GCA with a mean age at diagnosis of 76.9±8.3 years. The annual incidence was estimated at 7.42 (95% CI 6.57 to 8.27) cases of GCA per 100 000 people ≥50 years with a peak for patients aged 80–84 years (23.06 (95% CI 20.89 to 25.4)). The incidence was greater in women (10.06 (95% CI 8.7 to 11.5)) than in men (4.83 (95% CI 3.8 to 5.9)). No significant differences were found between geographical distribution and incidence throughout the year (p=0.125). The phenotypes at diagnosis were cranial in 1091 patients, extracranial in 337 patients and mixed in 170 patients.Conclusions This is the first study to estimate the incidence of GCA in Spain at a national level. We found a predominance among women and during the ninth decade of life with no clear variability according to geographical area or seasons of the year