Bernoulli and binomial proliferation on evolutionary graphs.

In this paper we introduce random proliferation models on graphs. We consider two types of particles: type-1/mutant/invader/red particles proliferates on a population of type-2/wild-type/resident/blue particles. Unlike the well-known Moran model on graphs -as introduced in Lieberman et al. (2005)-, type-1 particles can occupy in a single iteration several neighbouring sites previously occupied by type-2 particles. Two variants are considered, depending on the random distribution involving the proliferation mechanism: Bernoulli and binomial proliferation. By comparison with fixation probability of type-1 particles in the Moran process, critical parameters are introduced. Properties of proliferation are studied and some particular cases are analytically solved. Finally, by updating the parameters that drive the processes through a density-dependent mechanism, it is possible to capture additional relevant features as fluctuating waves of type-1 particles over long periods of time. In fact, the models can be adapted to tackle more general, complex and realistic situations.

Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator.

BACKGROUND AND OBJECTIVE: Unlike migraine and migraine with aura, little information exists regarding chronic migraine (CM) as a risk factor for cardiovascular disease. In this study we aim to determine whether an association between CM and endothelial dysfunction exists. METHODS: Individuals 18 years and older diagnosed with episodic migraine (EM) and CM according to ICHD criteria were studied. After an overnight fast and abstinence from vasoactive drugs, ultrasound studies were performed and blood samples taken from patients and matched controls according to internationally agreed on protocols. RESULTS: A total of 113 individuals were enrolled (35 CM, 37 EM, 41 controls). CM patients had a lower percentage of flow-mediated vasodilation (FMD; difference of means = 5.03%; p = 1.0E-6) and breath-holding index (BHI; difference of means 0.754; p = 2.0E-6), as well as increased carotid intima media thickness (cIMT; difference of means = 0.128 mm; p = 7.0E-5) than controls. The EM patients and controls comparison found similar, but less pronounced, differences: decreased BHI (p = 0.031), and increased cIMT (p = 0.028). Fibrinogen (r = 0.277; p = 0.006), C-reactive protein (r = 0.288; p = 0.003), and erythrocyte rate sedimentation (r = 0.298; p = 0.002) also correlated with cIMT, and inversely with BHImV and FMD. CONCLUSIONS: Migraine is associated with systemic and cerebral endothelial dysfunction demonstrated by ultrasound studies and biological markers. The degree of these changes was strongly associated with the severity of migraine. Our data indicate that migraine may be a cerebral disorder with systemic endothelial damage.

Comparative analysis of patellar tendon, achilles tendon and plantar fascia structure in indoor and outdoor football players: a novel cross-sectional pilot study.

Different sport modalities were associate with tendon adaptation or even tendon disturbances, such as volleyball, soccer or basketball. Purpose: the aim of the present study was to determine de difference between indoor and outdoor football players on patellar tendon (PT), Achilles tendon (AT), plantar fascia (FP) and Hoffa's fat pad thickness assessed with ultrasound imaging (USI). A cross-sectional study was developed with a total sample of 30 soccer players divided in two groups: outdoor group (n = 15) and indoor group (n = 15). The thickness of PT, AT, PF and Hoffa's fat pad has been assessed with USI. Hoffa's fat pad reported significant differences for the left side between groups (P = 0.026). The rest of variables did not show any significant difference (P < 0.05). The ultrasonography assessment of the thickness of the PT, AT and PF did not show differences between outdoor and indoor football players. Hoffa's fat pad resulted showed a significant decrease for outdoor soccer players with respect futsal players. Thus, it can be considered that the load stimuli received in both soccer players were not enough to produce structural adaptations in PT, AT and PF tissues.

Evolutionary regime transitions in structured populations.

The evolutionary dynamics of a finite population where resident individuals are replaced by mutant ones depends on its spatial structure. Usually, the population adopts the form of an undirected graph where the place occupied by each individual is represented by a vertex and it is bidirectionally linked to the places that can be occupied by its offspring. There are undirected graph structures that act as amplifiers of selection increasing the probability that the offspring of an advantageous mutant spreads through the graph reaching any vertex. But there also are undirected graph structures acting as suppressors of selection where this probability is less than that of the same individual placed in a homogeneous population. Here, firstly, we present the distribution of these evolutionary regimes for all undirected graphs with N ≤ 10 vertices. Some of them exhibit transitions between different regimes when the mutant fitness increases. In particular, as it has been already observed for small-order random graphs, we show that most graphs of order N ≤ 10 are amplifiers of selection. Secondly, we describe examples of amplifiers of order 7 that become suppressors from some critical value. In fact, for graphs of order N ≤ 7, we apply computer-aided techniques to symbolically compute their fixation probability and then their evolutionary regime, as well as the critical values for which they change their regime. Thirdly, the same technique is applied to some families of highly symmetrical graphs as a mean to explore methods of suppressing selection. The existence of suppression mechanisms that reverse an amplification regime when fitness increases could have a great interest in biology and network science. Finally, the analysis of all graphs from order 8 to order 10 reveals a complex and rich evolutionary dynamics, with multiple transitions between different regimes, which have not been examined in detail until now.

A method for validating Rent's rule for technological and biological networks.

Rent's rule is empirical power law introduced in an effort to describe and optimize the wiring complexity of computer logic graphs. It is known that brain and neuronal networks also obey Rent's rule, which is consistent with the idea that wiring costs play a fundamental role in brain evolution and development. Here we propose a method to validate this power law for a certain range of network partitions. This method is based on the bifurcation phenomenon that appears when the network is subjected to random alterations preserving its degree distribution. It has been tested on a set of VLSI circuits and real networks, including biological and technological ones. We also analyzed the effect of different types of random alterations on the Rentian scaling in order to test the influence of the degree distribution. There are network architectures quite sensitive to these randomization procedures with significant increases in the values of the Rent exponents.

Suppressors of selection.

Inspired by recent works on evolutionary graph theory, an area of growing interest in mathematical and computational biology, we present examples of undirected structures acting as suppressors of selection for any fitness value r > 1. This means that the average fixation probability of an advantageous mutant or invader individual placed at some node is strictly less than that of this individual placed in a well-mixed population. This leads the way to study more robust structures less prone to invasion, contrary to what happens with the amplifiers of selection where the fixation probability is increased on average for advantageous invader individuals. A few families of amplifiers are known, although some effort was required to prove it. Here, we use computer aided techniques to find an exact analytical expression of the fixation probability for some graphs of small order (equal to 6, 8 and 10) proving that selection is effectively reduced for r > 1. Some numerical experiments using Monte Carlo methods are also performed for larger graphs and some variants.

Increased incidence of thyroid cancer in Navarra (Spain). Evolution and clinical characteristics, 1986-2010. / Aumento de la incidencia de cáncer de tiroides en Navarra. Evolución y características clínicas, 1986-2010.

INTRODUCTION: The latest published studies show an increased incidence of thyroid cancer worldwide. The aim of this study was to analyze the changes in the incidence of thyroid cancer in Navarra and its clinical presentation regarding sex, histological subtype and size over the last 25 years. METHODS: Thyroid cancer incidence rates were calculated on the basis of data from the Cancer Registry of Navarra during 1986-2010. Clinical data were obtained from the historical cohort of the Hospital Registry of Cancer of Navarra, which includes all the new cases of differentiated thyroid carcinoma diagnosed and treated in the public health network of this Community in that period. RESULTS: The overall incidence of thyroid cancer in Navarra increased over the last 25 years, with an increase in the adjusted rate in men from 2.24 (1986-1990) to 5.85 (2006-2010) per 100,000 population/year (P<.001) and in women from 9.05 to 14.04, respectively (P<.001). This increase occurs only in papillary carcinoma. The clinical characteristics of 739 patients with differentiated thyroid cancer were studied. The mean age at diagnosis increased over the years and the predominance of women (about 80%) remains stable. Mean tumor size decreased over the five-year periods from 30.9 to 22.5mm (P<.001), the proportion of microcarcinomas (T1a) increased from 8.8% to 30% (P<.001) and, despite this increase, there were no statistical differences in the TNM stage at diagnosis during the study period. The distribution of histological variants of papillary and follicular carcinoma did not change over 25 years. CONCLUSIONS: During the period studied, the incidence of thyroid cancer increased in Navarra in both sexes. The increase occurred only in papillary carcinoma, without changes in the distribution of his histological variants. The increase in the proportion of T1a tumors is remarkable, but the TNM stage distribution was maintained. These results suggest an increase in the diagnosis of thyroid microcarcinomas due to changes in clinical practice, without ruling out a real increase in the incidence of papillary carcinoma in Navarra.

Factors Associated with Pulmonary Embolism Recurrence and the Benefits of Long-term Anticoagulant Therapy.

BACKGROUND: Venous thromboemboli tend to recur. However, the causative factors underlying pulmonary embolism recurrence are not well defined. AIMS: To explore the factors associated with pulmonary embolism recurrence. PATIENTS AND METHODS: Patients diagnosed with pulmonary emboli between 2004 and 2013 at our institution were enrolled. Duration of anticoagulant therapy, new episodes of venous thromboembolism, and deaths were recorded. RESULTS: Pulmonary embolism was diagnosed in 528 patients (median age: 76 years, interquartile range [IQR]: 16; male: 45%). The median follow-up time was 34 months (IQR: 52). In total, 477 patients completed ≥3 months of anticoagulation therapy. Permanent anticoagulation was indicated in 217 (45%) patients, and therapy was discontinued in 260 (55%) patients. Overall, 79 patients experienced a recurrence (5.6 per patient-year). Recurrence was significantly associated with anticoagulation discontinuation (4% vs. 27% of patients who maintained or discontinued therapy, respectively; P<0.001; 95% confidence interval -0.95, -0.86). The median duration between anticoagulation withdrawal and recurrence was 6.5 months (IQR: 23.25). Factors associated with recurrence were unprovoked pulmonary embolism (odds ratio [OR]: 0.45), a greater degree of pulmonary arterial obstruction (OR: 2.5), a delay in initiation of anticoagulation (OR: 3), and higher plasma D-dimer levels during treatment (OR: 2.3). Survival rates were improved for patients who maintained anticoagulation therapy relative to those who discontinued. CONCLUSION: Pulmonary embolism has a high recurrence rate. Permanent anticoagulant therapy should be considered for patients with idiopathic pulmonary embolism, a high thrombotic burden, and persistently elevated D-dimer levels during treatment, and for patients where therapy was initially delayed.

Exploring the topological sources of robustness against invasion in biological and technological networks.

For a network, the accomplishment of its functions despite perturbations is called robustness. Although this property has been extensively studied, in most cases, the network is modified by removing nodes. In our approach, it is no longer perturbed by site percolation, but evolves after site invasion. The process transforming resident/healthy nodes into invader/mutant/diseased nodes is described by the Moran model. We explore the sources of robustness (or its counterpart, the propensity to spread favourable innovations) of the US high-voltage power grid network, the Internet2 academic network, and the C. elegans connectome. We compare them to three modular and non-modular benchmark networks, and samples of one thousand random networks with the same degree distribution. It is found that, contrary to what happens with networks of small order, fixation probability and robustness are poorly correlated with most of standard statistics, but they depend strongly on the degree distribution. While community detection techniques are able to detect the existence of a central core in Internet2, they are not effective in detecting hierarchical structures whose topological complexity arises from the repetition of a few rules. Box counting dimension and Rent's rule are applied to show a subtle trade-off between topological and wiring complexity.

[Langerhans cell histiocytosis]. / Histiocitosis de células de Langerhans.

We describe the case of male diagnosed with histiocytosis of Langerhans cells. Histiocytosis X is an interstitial disease with a real incidence and an unknown prevalence that can be suspected due to epidemiological and radiological data. The diagnosis can be realized using BAL and/or anatomo-pathological study of a biopsy. The principal treatment is to give up the tobacco habit. Evolution can be favourable.

[Splenic disorders in internal medicines]. / Lesiones esplénicas en medicina interna.

The spleen is the largest lymphopoietic organ, containing 25% of total lymphoid mass. It participates in cellular and humoral immunity and intervenes in the renovation of red cells and the elimination of bacteria. Splenic functions are reduced when the spleen is absent, which entails, amongst other complications, greater susceptibility to suffering from sepsis due to encapsulated organisms. We present 6 clinical cases admitted to the Internal Medicine serve with splenic pathology and we make a review of the approach to be used. The spectrum of splenic lesions in internal medicine is very wide. On occasions, a splenic pathology can be suspected due to clinical history, physical exploration or because of cytopenias in the analyses. Different complementary tests are available for completing study of these lesions. A splenectomy can be carried out in case of diagnostic doubt, with the most frequent diagnoses being hepatic cirrhosis and lymphoma/leukaemia.

[Ectopic acromegaly due to a bronchial carcinoid]. / Acromegalia ectópica por carcinoide bronquial.

Tumours that cause ectopic acromegaly can do so through the secretion of GH or GHRH. One hundred cases of ectopic acromegaly due to secretion of GHRH have been described. Given the rarity of this pathology, we present a clinical case with the aim of contributing our diagnostic-therapeutic experience and the subsequent follow-up. We present the case of a patient with acromegaloid physical features that had evolved over several years. Concomitantly, he also presented other accompanying symptoms that were suggestive of a possible bronchial origin. Facing the clinical suspicion of acromegaly, we opted to confirm it biochemically and subsequently through image study. A hypophysary origin was ruled out, so we carried out screening for a bronchial neuroendocrine and/or gastrointestinal tumor as they are the most frequent localizations. The treatment of choice was surgical resection.

[Analysis of a series pheochromocytoma cases over 15 years]. / Serie de feocromocitomas durante 15 años en Navarra.

BACKGROUND: The pheochromocytoma is a catecholamine secreting tumour derived from chromaffin cells of the sympathetic nervous system. Eighty to eighty-five percent of these tumours are localized in the adrenal medulla. When pheocromocytomas are found outside the adrenal gland they are referred to as extra-adrenal pheochromocytomas or paragangliomas. The diagnosis is confirmed by elevation of catecholamines and the metanephrines in blood plasma and urine. Localization of the tumour should be done following biochemical diagnosis by means of CT scan and/or MRI. The treatment of choice is tumour resection by laparoscopic surgery. MATERIAL AND METHODS: A review was made of all patient medical histories diagnosed with pheochromocytoma confirmed by the pathology reports of Pathological anatomy of the Navarre hospital Complex (Anatomía patológica del Complejo hospitalario de Navarra A y B) between 1996 to 2010. Descriptive analysis was made using the IBM SPSS statistics program. RESULTS: Our series consists of 43 patients diagnosed with pheochromocytoma over a span of 15 years. The average age on presentation was 47 years. Among the younger patients specific genetic syndromes were found. Computerized tomography was the most widely used method of localization. Contradictory results were found regarding perioperative medical management protocols. All pheocromocytoma tumours in this series were benign. CONCLUSIONS: It is advisable to carry out a genetic study on patients under twenty. The biochemical indicators with the greatest diagnostic sensitivity were the levels of normetanephrine and metanephrine in urine. Surgery was the only treatment option.