167 research outputs found
The Field of Fashion Materialized: A Study of London Fashion Week
This article, based on two studies of the fashion industry examines one of its key institutions, London Fashion Week (LFW). Drawing on the work of Bourdieu, we argue that this event is a materialization of the field of fashion.We examine how LFW renders visible the boundaries, relational positions, capital and habitus at play in the field, reproducing critical divisions within it.As well as making visible the field, LFW is a ceremony of consecration within it that contributes to its reproduction. The central aim of this article is to develop an empirically grounded sense of field, reconciling this macro-structural concept with embodied and situated reality
Tool-Use Training in a Species of Rodent: The Emergence of an Optimal Motor Strategy and Functional Understanding
Tool use is defined as the manipulation of an inanimate object to change the position or form of a separate object. The expansion of cognitive niches and tool-use capabilities probably stimulated each other in hominid evolution. To understand the causes of cognitive expansion in humans, we need to know the behavioral and neural basis of tool use. Although a wide range of animals exhibit tool use in nature, most studies have focused on primates and birds on behavioral or psychological levels and did not directly address questions of which neural modifications contributed to the emergence of tool use. To investigate such questions, an animal model suitable for cellular and molecular manipulations is needed.) to use a rake-like tool with their forelimbs to retrieve otherwise out-of-reach rewards. Eventually, they mastered effective use of the tool, moving it in an elegant trajectory. After the degus were well trained, probe tests that examined whether they showed functional understanding of the tool were performed. Degus did not hesitate to use tools of different size, colors, and shapes, but were reluctant to use the tool with a raised nonfunctional blade. Thus, degus understood the functional and physical properties of the tool after extensive training.Our findings suggest that tool use is not a specific faculty resulting from higher intelligence, but is a specific combination of more general cognitive faculties. Studying the brains and behaviors of trained rodents can provide insights into how higher cognitive functions might be broken down into more general faculties, and also what cellular and molecular mechanisms are involved in the emergence of such cognitive functions
The Impact of Political Leaders' Profession and Education on Reforms
This paper analyzes whether the educational and professional background of a head of government matters for the implementation of market-liberalizing reforms. Employing panel data over the period 1970-2002, we present empirical evidence based on a novel data set covering profession and education of more than 500 political leaders from 73 countries. Our results show that entrepreneurs, professional scientists, and trained economists are significantly more reform oriented. Contrary, union executives tend to impede reforms. We also highlight interactions between profession and education with time in office and the political leaning of the ruling party
Nutrición enteral domiciliaria en España: registro Nadya del año 2011-2012
Objective: To describe the results of the home enteral
nutrition (HEN) registry of the NADYA-SENPE group in
2011 and 2012.
Material and methods: We retrieved the data of the patients
recorded from January 1st 2011 to December 31st 2012.
Results: There were 3021 patients in the registry
during the period from 29 hospitals, which gives 65.39 per
million inhabitants. 97.95% were adults, 51.4% male.
Mean age was 67.64 ± 19.1, median age was 72 years for
adults and 7 months for children. Median duration with
HEN was 351 days and for 97.5% was their first event
with HEN. Most patients had HEN because of neurological
disease (57.8%). Access route was nasogastric tube
for 43.5% and gastrostomy for 33.5%. Most patients had
limited activity level and, concerning autonomy, 54.8%
needed total help. Nutritional formula was supplied from
chemist’s office to 73.8% of patients and disposables,
when necessary, was supplied from hospitals to 53.8% of
patients. HEN was finished for 1,031 patients (34.1%)
during the period of study, 56.6% due to decease and
22.2% due to recovery of oral intake.
Conclusions: Data from NADYA-SENPE registry
must be explained cautiously because it is a non-compulsory
registry. In spite of the change in the methodology of
the registry in 2010, tendencies regarding HEN have been
maintained, other than oral routeObjetivos: Describir los resultados del registro de nutrición
enteral domiciliaria (NED) del grupo NADYASENPE
de los años 2011 y 12.
Material y métodos: Se recopilaron los datos introducidos
en el registro desde el 1 de enero de 2011 al 31 de diciembre
de 2012.
Resultados: Hubo 3021 pacientes en el registro durante
el periodo, procedentes de 29 hospitales, lo que da una
prevalencia de 65,39 casos por millón de habitantes.
97.95% fueron adultos, 51,4% varones. La edad media
fue 67,64 ± 19,1 años y la mediana 72 años para los adultos
y 7 meses para los niños. La duración media de la NED
fue 351 días y para el 97,5% fue el primer episodio con
NED. La mayoría de pacientes tenían NED por una enfermedad
neurológica (57,8%). La vía de acceso fue sonda
nasogástrica para el 43,5% y gastrostomía para el 33,5%.
La mayoría de pacientes tuvieron un nivel de actividad física
limitado y, respecto a la autonomía, 54,8% necesitaba
ayuda total. La fórmula de nutrición se suministró desde
las oficinas de farmacia para el 73,8% y los fungibles,
cuando fueron necesarios, desde los hospitales para el
53,8%. La NED se suspendió en 1.031 pacientes (34,1%)
durante el periodo de estudio, 56,6% debido a fallecimiento
y 22,2% debido a recuperación de la vía oral.
Conclusiones: Los datos del registro NADYA-SENPE
deben ser interpretados con precaución ya que se trata de
un registro voluntario. A pesar del cambio de metodología
del registro en 2010, las tendencias en NED se han mantenido,
salvo la importancia cuantitativa de la vía ora
Demethylation of the Coding Region Triggers the Activation of the Human Testis-Specific PDHA2 Gene in Somatic Tissues
Human PDHA2 is a testis-specific gene that codes for the E1α subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the −122 to −6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal promoter region and the consequent increase in PDHA2 mRNA levels. Bisulfite sequencing analysis revealed that DAC treatment induced a significant demethylation of the CpG island II (nucleotides +197 to +460) in PDHA2 coding region, while the promoter region remained highly methylated. Taken together with our previous results that show an in vivo correlation between PDHA2 expression and the demethylation of the CpG island II in testis germ cells, the present results show that internal methylation of the PDHA2 gene plays a part in its repression in somatic cells. In conclusion, our data support the novel finding that methylation of the PDHA2 coding region can inhibit gene transcription. This represents a key mechanism for absence of PDHA2 expression in somatic cells and a target for PDC therapy
A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies
Objective: Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. /
Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web‐based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht‐like diseases. A consensus‐based questionnaire was generated for each disease. /
Results: Twenty‐six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht‐like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. /
Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers
A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies
Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers
ANN multiscale model of anti-HIV Drugs activity vs AIDS prevalence in the US at county level based on information indices of molecular graphs and social networks
[Abstract] This work is aimed at describing the workflow for a methodology that combines chemoinformatics and pharmacoepidemiology methods and at reporting the first predictive model developed with this methodology. The new model is able to predict complex networks of AIDS prevalence in the US counties, taking into consideration the social determinants and activity/structure of anti-HIV drugs in preclinical assays. We trained different Artificial Neural Networks (ANNs) using as input information indices of social networks and molecular graphs. We used a Shannon information index based on the Gini coefficient to quantify the effect of income inequality in the social network. We obtained the data on AIDS prevalence and the Gini coefficient from the AIDSVu database of Emory University. We also used the Balaban information indices to quantify changes in the chemical structure of anti-HIV drugs. We obtained the data on anti-HIV drug activity and structure (SMILE codes) from the ChEMBL database. Last, we used Box-Jenkins moving average operators to quantify information about the deviations of drugs with respect to data subsets of reference (targets, organisms, experimental parameters, protocols). The best model found was a Linear Neural Network (LNN) with values of Accuracy, Specificity, and Sensitivity above 0.76 and AUROC > 0.80 in training and external validation series. This model generates a complex network of AIDS prevalence in the US at county level with respect to the preclinical activity of anti-HIV drugs in preclinical assays. To train/validate the model and predict the complex network we needed to analyze 43,249 data points including values of AIDS prevalence in 2,310 counties in the US vs ChEMBL results for 21,582 unique drugs, 9 viral or human protein targets, 4,856 protocols, and 10 possible experimental measures.Ministerio de Educación, Cultura y Deportes; AGL2011-30563-C03-0
Semi-Synthetic Analogues of Cryptolepine as a Potential Source of Sustainable Drugs for the Treatment of Malaria, Human African Trypanosomiasis and Cancer
YesThe prospect of eradicating malaria continues to be challenging in the face of increasing
parasite resistance to antimalarial drugs so that novel antimalarials active against asexual,
sexual, and liver-stage malaria parasites are urgently needed. In addition, new antimalarials
need to be affordable and available to those most in need and, bearing in mind climate
change, should ideally be sustainable. The West African climbing shrub Cryptolepis
sanguinolenta is used traditionally for the treatment of malaria; its principal alkaloid,
cryptolepine (1), has been shown to have antimalarial properties, and the synthetic
analogue 2,7-dibromocryptolepine (2) is of interest as a lead toward new antimalarial
agents. Cryptolepine (1) was isolated using a two-step Soxhlet extraction of C.
sanguinolenta roots, followed by crystallization (yield 0.8% calculated as a base with
respect to the dried roots). Semi-synthetic 7-bromo- (3), 7, 9-dibromo- (4), 7-iodo- (5), and
7, 9-dibromocryptolepine (6) were obtained in excellent yields by reaction of 1 with
N-bromo- or N-iodosuccinimide in trifluoroacetic acid as a solvent. All compounds
were active against Plasmodia in vitro, but 6 showed the most selective profile with
respect to Hep G2 cells: P. falciparum (chloroquine-resistant strain K1), IC50 = 0.25 µM, SI
= 113; late stage, gametocytes, IC50 = 2.2 µM, SI = 13; liver stage, P. berghei sporozoites
IC50 = 6.13 µM, SI = 4.6. Compounds 3–6 were also active against the emerging zoonotic species P. knowlesi with 5 being the most potent (IC50 = 0.11 µM). In addition, 3–6 potently
inhibited T. brucei in vitro at nM concentrations and good selectivity with 6 again being the
most selective (IC50 = 59 nM, SI = 478). These compounds were also cytotoxic to wild-type
ovarian cancer cells as well as adriamycin-resistant and, except for 5, cisplatin-resistant
ovarian cancer cells. In an acute oral toxicity test in mice, 3–6 did not exhibit toxic effects at
doses of up to 100 mg/kg/dose × 3 consecutive days. This study demonstrates that C.
sanguinolenta may be utilized as a sustainable source of novel compounds that may lead
to the development of novel agents for the treatment of malaria, African trypanosomiasis,
and cancer
- …