209 research outputs found
The Muslim problematic: Muslims, state schools and security
Muslims are folk-devils that mark the ubiquitous moral panic. For some, the idea of the Muslim problematic signifies a long and worrying trend of creeping ‘Islamification’ of state schools. For others, the discourse of the Muslim problematic reflects the ongoing racial patholigisation of Britain’s minoritised communities. One thing is for certain, the current debate marks a significant moment in the nature and function of the neoliberal state as it reframes race relation policy in Britain in the light of the security agenda. The Trojan Horse affair, surrounding claims of infiltration of radical Islam in state-run schools, marks a significant moment in the embedding of the security agenda in Britain’s inner city schools through the medium of the Prevent agenda. It argues that one of the best ways of understanding the security agenda is by locating it within a broader sociological and historical context of the functioning of the racial state
Interference control in children with attention deficit/hyperactivity disorder
The view that Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a diminished ability to control interfference is controversial and based exclusively on results of (verbal)-visual interference tasks, primarily the Stroop Color Word task. The present study compares medication-naïve children with ADHD (n∈=∈35 and n∈=∈51 in Experiments 1 and 2, respectively) with normal controls (n∈=∈26 and n∈=∈32, respectively) on two interference tasks to assess interference control in both the auditory and the visual modality: an Auditory Stroop task and a Simon task. Both groups showed reliable but equal degrees of interference on both tasks, suggesting that children with ADHD do not differ from normal controls in their ability to control interference in either modality. © 2008 The Author(s)
Elevated photic response is followed by a rapid decay and depressed state in ictogenic networks
Objective: The switch between nonseizure and seizure states involves profound alterations in network excitability and synchrony. In this study, we aimed to identify and compare features of neural excitability and dynamics across multiple zebrafish seizure and epilepsy models.
Methods: Inspired by video-electroencephalographic recordings in patients, we developed a framework to study spontaneous and photically evoked neural and locomotor activity in zebrafish larvae, by combining high-throughput behavioral tracking and whole-brain in vivo two-photon calcium imaging.
Results: Our setup allowed us to dissect behavioral and physiological features that are divergent or convergent across multiple models. We observed that spontaneous locomotor and neural activity exhibit great diversity across models. Nonetheless, during photic stimulation, hyperexcitability and rapid response dynamics were well conserved across multiple models, highlighting the reliability of photically evoked activity for high-throughput assays. Intriguingly, in several models, we observed that the initial elevated photic response is often followed by rapid decay of neural activity and a prominent depressed state. Elevated photic response and following depressed state in seizure-prone networks are significantly reduced by the antiseizure medication valproic acid. Finally, rapid decay and depression of neural activity following photic stimulation temporally overlap with slow recruitment of astroglial calcium signals that are enhanced in seizure-prone networks.
Significance: We argue that fast decay of neural activity and depressed states following photic response are likely due to homeostatic mechanisms triggered by excessive neural activity. An improved understanding of the interplay between elevated and depressed excitability states might suggest tailored epilepsy therapies.
Keywords: astroglia; calcium imaging; depressed state; elevated state; epilepsy; high-throughput behavior; hyperexcitability; photic stimulation; seizure; zebrafis
Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis
Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells’ redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects
A Pilot Initiative to Deliver Community-based Psychiatric Services in Rural Haiti After the 2010 Earthquake
Background: Worldwide, there is a gap between the burden of mental distress and disorder and access to mental health care. This gap is particularly large in low- and middle-income countries (LMICs). After the 2010 earthquake in Haiti, the international health care organizations Partners in Health and Zanmi Lasante worked to expand local mental health services in rural Haiti. Objective: The aims of this study are to describe clinical characteristics of the patients served during a pilot project to deliver community-based psychiatric services in rural Haiti and to show how this experience complements the Mental Health Gap Action Programme (“mhGAP”), a tool developed by the World Health Organization to support mental health care delivery by nonspecialists in LMICs. Methods: The pilot was conducted in March 2011. A visiting psychiatrist traveled to rural Haiti and paired with local clinicians to evaluate patients and to support quality improvement practices in psychiatric care. Patients received a standard neuropsychiatric evaluation. mhGAP was an important clinical reference. To assess the experience, we conducted a retrospective chart review of outpatient encounters. Findings: Sixty-five patients presented with a wide range of common psychiatric, neurologic, and general medical conditions. Forty-nine of these patients (75%) reported primary problems subsumed by an mhGAP module. Fifteen patients (23%) reported headache as their chief complain, a condition that is not currently covered by mhGAP. Surprisingly, only 3 patients (5%), reported earthquake-related distress. Conclusions: Our clinical data reinforce the need for provision of standard psychiatric and neurologic services in LMICs. Such services ought to accompany interventions targeted specifically at disaster-related problems. Clinical situations falling outside existing mhGAP modules inspired the development of supplemental treatment protocols. These observations informed coordinated efforts at Zanmi Lasante to build a sustainable, integrated mental health system in Haiti that may be relevant to other resource-limited settings
Long-term mortality prediction after operations for type A ascending aortic dissection
<p>Abstract</p> <p>Background</p> <p>There are few long-term mortality prediction studies after acute aortic dissection (AAD) Type A and none were performed using new models such as neural networks (NN) or support vector machines (SVM) which may show a higher discriminatory potency than standard multivariable models.</p> <p>Methods</p> <p>We used 32 risk factors identified by Literature search and previously assessed in short-term outcome investigations. Models were trained (50%) and validated (50%) on 2 random samples from a consecutive 235-patient cohort. NN were run only on patients with complete data for all included variables (N = 211); SVM on the overall group. Discrimination was assessed by receiver operating characteristic area under the curve (AUC) and Gini's coefficients along with classification performance.</p> <p>Results</p> <p>There were 84 deaths (36%) occurring at 564 ± 48 days (95%CI from 470 to 658 days). Patients with complete variables had a slightly lower death rate (60 of 211, 28%). NN classified 44 of 60 (73%) dead patients and 147 of 151 (97%) long-term survivors using 5 covariates: immediate post-operative chronic renal failure, circulatory arrest time, the type of surgery on ascending aorta plus hemi-arch, extracorporeal circulation time and the presence of Marfan habitus. Global accuracies of training and validation NN were excellent with AUC respectively 0.871 and 0.870 but classification errors were high among patients who died. Training SVM, using a larger number of covariates, showed no false negative or false positive cases among 118 randomly selected patients (error = 0%, AUC 1.0) whereas validation SVM, among 117 patients, provided 5 false negative and 11 false positive cases (error = 22%, AUC 0.821, p < 0.01 versus NN results). An html file was produced to adopt and manipulate the selected parameters for practical predictive purposes.</p> <p>Conclusions</p> <p>Both NN and SVM accurately selected a few operative and immediate post-operative factors and the Marfan habitus as long-term mortality predictors in AAD Type A. Although these factors were not new per se, their combination may be used in practice to index death risk post-operatively with good accuracy.</p
Phylogenetic Diversity and Genotypical Complexity of H9N2 Influenza A Viruses Revealed by Genomic Sequence Analysis
H9N2 influenza A viruses have become established worldwide in terrestrial poultry and wild birds, and are occasionally transmitted to mammals including humans and pigs. To comprehensively elucidate the genetic and evolutionary characteristics of H9N2 influenza viruses, we performed a large-scale sequence analysis of 571 viral genomes from the NCBI Influenza Virus Resource Database, representing the spectrum of H9N2 influenza viruses isolated from 1966 to 2009. Our study provides a panoramic framework for better understanding the genesis and evolution of H9N2 influenza viruses, and for describing the history of H9N2 viruses circulating in diverse hosts. Panorama phylogenetic analysis of the eight viral gene segments revealed the complexity and diversity of H9N2 influenza viruses. The 571 H9N2 viral genomes were classified into 74 separate lineages, which had marked host and geographical differences in phylogeny. Panorama genotypical analysis also revealed that H9N2 viruses include at least 98 genotypes, which were further divided according to their HA lineages into seven series (A–G). Phylogenetic analysis of the internal genes showed that H9N2 viruses are closely related to H3, H4, H5, H7, H10, and H14 subtype influenza viruses. Our results indicate that H9N2 viruses have undergone extensive reassortments to generate multiple reassortants and genotypes, suggesting that the continued circulation of multiple genotypical H9N2 viruses throughout the world in diverse hosts has the potential to cause future influenza outbreaks in poultry and epidemics in humans. We propose a nomenclature system for identifying and unifying all lineages and genotypes of H9N2 influenza viruses in order to facilitate international communication on the evolution, ecology and epidemiology of H9N2 influenza viruses
Artificial Neural Networks Versus Multiple Logistic Regression to Predict 30-Day Mortality After Operations For Type A Ascending Aortic Dissection§
There are few comparative reports on the overall accuracy of neural networks (NN), assessed only versus multiple logistic regression (LR), to predict events in cardiovascular surgery studies and none has been performed among acute aortic dissection (AAD) Type A patients. OBJECTIVES: We aimed at investigating the predictive potential of 30-day mortality by a large series of risk factors in AAD Type A patients comparing the overall performance of NN versus LR. METHODS: We investigated 121 plus 87 AAD Type A patients consecutively operated during 7 years in two Centres. Forced and stepwise NN and LR solutions were obtained and compared, using receiver operating characteristic area under the curve (AUC) and their 95% confidence intervals (CI) and Gini's coefficients. Both NN and LR models were re-applied to data from the second Centre to adhere to a methodological imperative with NN. RESULTS: Forced LR solutions provided AUC 87.9+/-4.1% (CI: 80.7 to 93.2%) and 85.7+/-5.2% (CI: 78.5 to 91.1%) in the first and second Centre, respectively. Stepwise NN solution of the first Centre had AUC 90.5+/-3.7% (CI: 83.8 to 95.1%). The Gini's coefficients for LR and NN stepwise solutions of the first Centre were 0.712 and 0.816, respectively. When the LR and NN stepwise solutions were re-applied to the second Centre data, Gini's coefficients were, respectively, 0.761 and 0.850. Few predictors were selected in common by LR and NN models: the presence of pre-operative shock, intubation and neurological symptoms, immediate post-operative presence of dialysis in continuous and the quantity of post-operative bleeding in the first 24 h. The length of extracorporeal circulation, post-operative chronic renal failure and the year of surgery were specifically detected by NN. CONCLUSIONS: Different from the International Registry of AAD, operative and immediate post-operative factors were seen as potential predictors of short-term mortality. We report a higher overall predictive accuracy with NN than with LR. However, the list of potential risk factors to predict 30-day mortality after AAD Type A by NN model is not enlarged significantly
Evidence of Expanded Host Range and Mammalian-Associated Genetic Changes in a Duck H9N2 Influenza Virus Following Adaptation in Quail and Chickens
H9N2 avian influenza viruses continue to circulate worldwide; in Asia, H9N2 viruses have caused disease outbreaks and established lineages in land-based poultry. Some H9N2 strains are considered potentially pandemic because they have infected humans causing mild respiratory disease. In addition, some of these H9N2 strains replicate efficiently in mice without prior adaptation suggesting that H9N2 strains are expanding their host range. In order to understand the molecular basis of the interspecies transmission of H9N2 viruses, we adapted in the laboratory a wildtype duck H9N2 virus, influenza A/duck/Hong Kong/702/79 (WT702) virus, in quail and chickens through serial lung passages. We carried out comparative analysis of the replication and transmission in quail and chickens of WT702 and the viruses obtained after 23 serial passages in quail (QA23) followed by 10 serial passages in chickens (QA23CkA10). Although the WT702 virus can replicate and transmit in quail, it replicates poorly and does not transmit in chickens. In contrast, the QA23CkA10 virus was very efficient at replicating and transmitting in quail and chickens. Nucleotide sequence analysis of the QA23 and QA23CkA10 viruses compared to the WT702 virus indicated several nucleotide substitutions resulting in amino acid changes within the surface and internal proteins. In addition, a 21-amino acid deletion was found in the stalk of the NA protein of the QA23 virus and was maintained without further modification in the QA23CkA10 adapted virus. More importantly, both the QA23 and the QA23CkA10 viruses, unlike the WT702 virus, were able to readily infect mice, produce a large-plaque phenotype, showed faster replication kinetics in tissue culture, and resulted in the quick selection of the K627 amino acid mammalian-associated signature in PB2. These results are in agreement with the notion that adaptation of H9 viruses to land-based birds can lead to strains with expanded host range
Programmable Ligand Detection System in Plants through a Synthetic Signal Transduction Pathway
There is an unmet need to monitor human and natural environments for substances that are intentionally or unintentionally introduced. A long-sought goal is to adapt plants to sense and respond to specific substances for use as environmental monitors. Computationally re-designed periplasmic binding proteins (PBPs) provide a means to design highly sensitive and specific ligand sensing capabilities in receptors. Input from these proteins can be linked to gene expression through histidine kinase (HK) mediated signaling. Components of HK signaling systems are evolutionarily conserved between bacteria and plants. We previously reported that in response to cytokinin-mediated HK activation in plants, the bacterial response regulator PhoB translocates to the nucleus and activates transcription. Also, we previously described a plant visual response system, the de-greening circuit, a threshold sensitive reporter system that produces a visual response which is remotely detectable and quantifiable.We describe assembly and function of a complete synthetic signal transduction pathway in plants that links input from computationally re-designed PBPs to a visual response. To sense extracellular ligands, we targeted the computational re-designed PBPs to the apoplast. PBPs bind the ligand and develop affinity for the extracellular domain of a chemotactic protein, Trg. We experimentally developed Trg fusions proteins, which bind the ligand-PBP complex, and activate intracellular PhoR, the HK cognate of PhoB. We then adapted Trg-PhoR fusions for function in plants showing that in the presence of an external ligand PhoB translocates to the nucleus and activates transcription. We linked this input to the de-greening circuit creating a detector plant.Our system is modular and PBPs can theoretically be designed to bind most small molecules. Hence our system, with improvements, may allow plants to serve as a simple and inexpensive means to monitor human surroundings for substances such as pollutants, explosives, or chemical agents
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