Law, Liberty and the Rule of Law (in a Constitutional Democracy)

In the hunt for a better--and more substantial--awareness of the “law,” The author intends to analyze the different notions related to the “rule of law” and to criticize the conceptions that equate it either to the sum of “law” and “rule” or to the formal assertion that “law rules,” regardless of its relationship to certain principles, including both “negative” and “positive” liberties. Instead, he pretends to scrutinize the principles of the “rule of law,” in general, and in a “constitutional democracy,” in particular, to conclude that the tendency to reduce the “democratic principle” to the “majority rule” (or “majority principle”), i.e. to whatever pleases the majority, as part of the “positive liberty,” is contrary both to the “negative liberty” and to the “rule of law” itself

The best fit for the observed galaxy Counts-in-Cell distribution function

The Sloan Digital Sky Survey (SDSS) is the first dense redshift survey encompassing a volume large enough to find the best analytic probability density function that fits the galaxy Counts-in-Cells distribution $f_V(N)$, the frequency distribution of galaxy counts in a volume $V$. Different analytic functions have been previously proposed that can account for some of the observed features of the observed frequency counts, but fail to provide an overall good fit to this important statistical descriptor of the galaxy large-scale distribution. Our goal is to find the probability density function that better fits the observed Counts-in-Cells distribution $f_V(N)$. We have made a systematic study of this function applied to several samples drawn from the SDSS. We show the effective ways to deal with incompleteness of the sample (masked data) in the calculation of $f_V(N)$. We use LasDamas simulations to estimate the errors in the calculation. We test four different distribution functions to find the best fit: the Gravitational Quasi-Equilibrium distribution, the Negative Binomial Distribution, the Log Normal distribution and the Log Normal Distribution including a bias parameter. In the two latter cases, we apply a shot-noise correction to the distributions assuming the local Poisson model. We show that the best fit for the Counts-in-Cells distribution function is provided by the Negative Binomial distribution. In addition, at large scales the Log Normal distribution modified with the inclusion of the bias term also performs a satisfactory fit of the empirical values of $f_V(N)$. Our results demonstrate that the inclusion of a bias term in the Log Normal distribution is necessary to fit the observed galaxy Count-in-Cells distribution function.Comment: 12 pages, 16 figures. Accepted for publication in Astronomy & Astrophysic

Evaluación de Quassia amara como tratamiento contra la varroosis en tres apiarios del municipio de León, Nicaragua

DOI: http://dx.doi.org/10.5377/universitas.v5i1.1482 UNIVERSITAS (León): Revista Científica de la UNAN León Vol.5(1) 2014, pp 100-106Se realizó un estudio experimental en tres apiarios con las mismas condiciones físicas y ambientales con el fin de evaluar la eficacia del extracto acuoso Quassia amara como tratamiento contra Varroa destructor utilizando para esto cinco grupos de tratamiento: Colmena ST: Sin tratamiento, es el control y cuatro colmenas a las que se les aplicó el extracto de Quassia amara en diferentes concentraciones: Colmena A: solución madre (M) 100% (1 kg materia bruta/10 l de agua); Colmena B: dilución I = Una parte de solución M más 4 partes de agua (20%); Colmena C: dilución II = Una parte de la dilución I más una parte de agua (10%); Colmena D: dilución III = Una parte de dilución II más una parte de agua (5%). Se realizaron seis aplicaciones mediante aspersión con intervalo de cuatro días. Los índices de infestación fueron valorados mediante conteos de la carga parasitaria en abejas adultas de cada colmena y las muestras se recolectaron en los siguientes momentos: Al realizar la primera, tercera y última aplicaciones, y 21 días después de la última. La extensión de invasión en crías se determinó en la primera y última aplicaciones y 21 días después. En total se trabajaron 60 muestras de abejas adultas de 150 a 200 especímenes y 45 fragmentos de panales de cría operculada de 10x10 cm. Se encontró que la dilución I fue la más efectiva sobre el ácaro en abejas adultas, con el mejor resultado a la cuarta semana del inicio de la aplicación (eficacia = 62%) mientras que en crías la más efectiva fue la dilución IV (eficacia = 23,10%). La planta Quassia amara brinda una alternativa prometedora de posible futura integración a las medidas con que los productores enfrentan el problema de la varroosis. La información recopilada contribuirá a la elaboración de un programa de control de esta enfermedad. DOI: http://dx.doi.org/10.5377/universitas.v5i1.1482 UNIVERSITAS (León): Revista Científica de la UNAN León Vol.5(1) 2014, pp 100-10

Mecanismos de negación en el infarto de miocardio: su relación con las variables psicológicas y la evolución a corto plazo

A partir de una muestra seleccionada de 97 varones con primer infarto de miocardio, se han estudiado 67 pacientes para aclarar la influencia de los mecanismos de negación (MN) en la evolución psicológica y cardiológica. No hubo diferencias entre los negadores y los no negadores en cuanto a la evolución cardiológica, pero los negadores presentaron menos ansiedad y menos reacciones depresivas en la unidad coronaria y un mes después, así como menos psicopatología en general. En la última evaluación, un año después del alta hospitalaria (n: 52) no hubo diferencias entre los negadores y los no negadores en lo que respecta a la petición de asistencia psiquiátric

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Current and prospective pharmacotherapies for the treatment of pleural mesothelioma

Introduction: Mesothelioma is a rare asbestos-linked cancer with an expected incidence peak between 2015–2030. Therapies remain ineffective, thus developing and testing novel treatments is important for both oncologists and researchers. Areas covered: After describing mesothelioma and the shortcomings of current therapies, the article discusses numerous therapies in turn such as immunotherapy (passive and active), gene therapy (such as suicide gene therapy) and targeted therapy such as tyrosine kinase inhibitors. The bases for different therapies and clinical trials at different phases are also described. The article concludes by detailing possible reasons for therapy failure. Expert opinion: Despite the many attempts to uncover new therapeutic options, mesothelioma is still an orphan disease, complicated by factors such as the inflammatory microenvironment and low mutational load. Our opinion is that uncovering the biological mechanisms behind mesothelioma development will assist therapy development. The lack of efficacy of tyrosine kinase inhibitors and modest anti-angiogenic activity indicates a less relevant role for tumor cell proliferation and neoangiogenesis, thus the shortcut of treating mesothelioma with therapies from other cancers may be unsound. Conversely, many lines of evidence indicate that focussing on the survival mechanisms that tumor cells exploit may yield better therapeutics, particularly nutrition and cellular machinery

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

North African Influences and Potential Bias in Case-Control Association Studies in the Spanish Population

BACKGROUND: Despite the limited genetic heterogeneity of Spanish populations, substantial evidences support that historical African influences have not affected them uniformly. Accounting for such population differences might be essential to reduce spurious results in association studies of genetic factors with disease. Using ancestry informative markers (AIMs), we aimed to measure the African influences in Spanish populations and to explore whether these might introduce statistical bias in population-based association studies. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 93 AIMs in Spanish (from the Canary Islands and the Iberian Peninsula) and Northwest Africans, and conducted population and individual-based clustering analyses along with reference data from the HapMap, HGDP-CEPH, and other sources. We found significant differences for the Northwest African influence among Spanish populations from as low as ≈ 5% in Spanish from the Iberian Peninsula to as much as ≈ 17% in Canary Islanders, whereas the sub-Saharan African influence was negligible. Strikingly, the Northwest African ancestry showed a wide inter-individual variation in Canary Islanders ranging from 0% to 96%, reflecting the violent way the Islands were conquered and colonized by the Spanish in the XV century. As a consequence, a comparison of allele frequencies between Spanish samples from the Iberian Peninsula and the Canary Islands evidenced an excess of markers with significant differences. However, the inflation of p-values for the differences was adequately controlled by correcting for genetic ancestry estimates derived from a reduced number of AIMs. CONCLUSIONS/SIGNIFICANCE: Although the African influences estimated might be biased due to marker ascertainment, these results confirm that Northwest African genetic footprints are recognizable nowadays in the Spanish populations, particularly in Canary Islanders, and that the uneven African influences existing in these populations might increase the risk for false positives in association studies. Adjusting for population stratification assessed with a few dozen AIMs would be sufficient to control this effect