4,076 research outputs found
Children, family and the state : revisiting public and private realms
The state is often viewed as part of the impersonal public sphere in opposition to the private family as a locus of warmth and intimacy. In recent years this modernist dichotomy has been challenged by theoretical and institutional trends which have altered the relationship between state and family. This paper explores changes to both elements of the dichotomy that challenge this relationship: a more fragmented family structure and more individualised and networked support for children. It will also examine two new elements that further disrupt any clear mapping between state/family and public/private dichotomies: the third party role of the child in family/state affairs and children's application of virtual technology that locates the private within new cultural and social spaces. The paper concludes by examining the rise of the 'individual child' hitherto hidden within the family/state dichotomy and the implications this has for intergenerational relations at personal and institutional levels
Human rights and public education
This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its European neighbours in implementing citizenship education. Second, a comparison with France shows that the latest UK reforms bring us up to 1789. Third, the twentieth-century second-generation social and economic rights are still anathema in the UK. Fourth, the failure to come to terms with Empire and especially the slave trade means that the UK’s attitude to third-generation rights, especially the right of peoples to self-determination, is heavily compromised. Taking into account the points I raise, citizenship education in the UK might look very different
Factors associated with disability in patients with rheumatoid arthritis with persistent moderate disease activity: a retrospective cohort study
Background: Many patients with rheumatoid arthritis (RA) do not attain remission/low disease activity, remaining in a moderate disease activity state (MDAS) with ongoing disability and impaired quality of life (QoL). If patients in persistent MDAS with poor future outcomes could be prospectively identified, they could arguably be treated more intensively. We evaluated baseline factors predicting function (Health Assessment Questionnaire-Disability Index [HAQ-DI] scores) and QoL (3-level EuroQol-5 dimensions questionnaire [EQ-5D-3L] index scores) at 12 months in patients with RA in persistent MDAS in a real-world setting.
Methods: Patients with persistent MDAS (Disease Activity Score for 28-joint count based on erythrocyte sedimentation rate [DAS28-ESR] 3.2-5.1 on at least two consecutive outpatient appointments over 12 months) were identified retrospectively from Guy's Hospital RA Centre and analysed in two groups: (1) biologic naïve at baseline or (2) receiving/ever received biologics. The baseline timepoint was the second-visit MDAS DAS28-ESR score; the endpoint was the closest visit to 12 months. Linear regression analyses evaluated relationships between baseline variables and (1) 12-month HAQ-DI scores, (2) 12-month rank-transformed EQ-5D-3L index scores, (3) 12-month changes in HAQ-DI scores, and (4) 12-month changes in EQ-5D-3L index scores.
Results: The analysis included 207 biologic-naïve and 188 biologic-experienced patients. All patients had moderate disability (mean HAQ-DI 1.21 and 1.46) and impaired QoL (mean EQ-5D-3L index scores 0.52 and 0.50). Many reported moderate/severe pain (93 and 96%) and showed little change in HAQ-DI and EQ-5D-3L index scores over 12 months. In both biologic-naïve and biologic-experienced groups, multivariate analysis revealed a significant association between baseline HAQ-DI scores and endpoint HAQ-DI scores (β = 0.67, P < 0.001 and β = 0.76, P < 0.001, respectively), 12-month changes in HAQ-DI scores (both β = - 0.21, P < 0.001), and 12-month EQ-5D-3L index scores (β = - 0.57, P < 0.001 and β = - 0.29, P = 0.004, respectively). Baseline EQ-5D-3L index scores were significantly associated with 12-month changes in EQ-5D-3L index scores in both groups (β = - 0.73, P < 0.001 and β = - 0.40, P = 0.003, respectively).
Conclusions: Patients with RA in persistent MDAS experience substantial ongoing physical disability, poor QoL, and pain. HAQ-DI is an important predictor of future disability and reduced QoL, supporting current national recommendations to measure HAQ-DI in routine care
Combined Docking and Quantum Chemical Study on CYP-mediated Metabolism of Estrogens in Man
Long-term exposure
to estrogens seriously increases the incidence
of various diseases including breast cancer. Experimental studies
indicate that cytochrome P450 (CYP) enzymes catalyze the bioactivation
of estrogens to catechols, which can exert their harmful effects via
various routes. It has been shown that the 4-hydroxylation pathway
of estrogens is the most malign, while 2-hydroxylation is considered
a benign pathway. It is also known experimentally that with increasing
unsaturation of ring B of estrogens the prevalence of the 4-hydroxylation
pathway significantly increases. In this study, we used a combination
of structural analysis, docking, and quantum chemical calculations
at the B3LYP/6-311+G* level to investigate the factors that influence
the regioselectivity of estrogen metabolism in man. We studied the
structure of human estrogen metabolizing enzymes (CYP1A1, CYP1A2,
CYP1B1, and CYP3A4) in complex with estrone using docking and investigated
the susceptibility of estrone, equilin, and equilenin (which only
differ in the unsaturation of ring B) to undergo 2- and 4-hydroxylation
using several models of CYP enzymes (Compound I, methoxy, and phenoxy
radical). We found that even the simplest models could account for
the experimental difference between the 2- and 4- hydroxylation pathways
and thus might be used for fast screening purposes. We also show that
reactivity indices, specifically in this case the radical and nucleophilic
condensed Fukui functions, also correctly predict the likeliness of
estrogen derivatives to undergo 2- or 4-hydroxylation
Improved validation framework and R-package for artificial neural network models
Validation is a critical component of any modelling process. In artificial neural network (ANN) modelling, validation generally consists of the assessment of model predictive performance on an independent validation set (predictive validity). However, this ignores other aspects of model validation considered to be good practice in other areas of environmental modelling, such as residual analysis (replicative validity) and checking the plausibility of the model in relation to a priori system understanding (structural validity). In order to address this shortcoming, a validation framework for ANNs is introduced in this paper that covers all of the above aspects of validation. In addition, the validann R-package is introduced that enables these validation methods to be implemented in a user-friendly and consistent fashion. The benefits of the framework and R-package are demonstrated for two environmental modelling case studies, highlighting the importance of considering replicative and structural validity in addition to predictive validity
Breaking down automaticity: Case ambiguity and the shift to reflective approaches in clinical reasoning
Context: Two modes of case processing have been shown to underlie diagnostic judgements: analytical and non-analytical reasoning. An optimal form of clinical reasoning is suggested to combine both modes. Conditions leading doctors to shift from the usual mode of non-analytical reasoning to reflective reasoning have not been identified. This paper reports a study aimed at exploring these conditions by investigating the effects of ambiguity of clinical cases on clinical reasoning. Methods: Participants were 16 internal medicine residents in the Brazilian state of Ceará. They were asked to diagnose 20 clinical cases and recall case information. The independent variable was the degree of ambiguity of clinical cases, with 2 levels: straightforward (i.e. non-ambiguous) and ambiguous. Dependent variables were processing time, diagnostic accuracy and proposition per category recalled. Data were analysed using a repeated measures design. Results: Participants processed straightforward cases faster and more accurately than ambiguous ones. The proportion of text propositions recalled was significantly lower (t[15] = 2.29, P = 0.037) in ambiguous cases, and an interaction effect between case version and proposition category was also found (F[5, 75] = 4.52, P = 0.001, d = 0.232, observed power = 0.962). Furthermore, participants recalled significantly more literal propositions from the ambiguous cases than from the straightforward cases (t[15] = 2.28, P = 0.037). Conclusions: Ambiguity of clinical cases was shown to lead residents to switch from automatic to reflective reasoning, as indicated by longer processing time, and more literal propositions recalled in ambiguous cases
Shortest Path Problems on a Polyhedral Surface
We develop algorithms to compute shortest path edge sequences, Voronoi diagrams, the Fréchet distance, and the diameter for a polyhedral surface
A Homolog of the Vaccinia Virus D13L Rifampicin Resistance Gene is in the Entomopoxvirus of the Parasitic wasp, Diachasmimorpha longicaudata
The parasitic wasp, Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae), introduces an entomopoxvirus (DlEPV) into its Caribbean fruit fly host, Anastrepha suspensa. (Loew) (Diptera: Tephritidae), during oviposition. DlEPV has a 250–300 kb unipartite dsDNA genome, that replicates in the cytoplasm of the host's hemocytes, and inhibits the host's encapsulation response. The putative proteins encoded by several DlEPV genes are highly homologous with those of poxviruses, while others appear to be DlEPV specific. Here, a 2.34 kb sequence containing a 1.64 kb DlEPV open reading frame within a cloned 4.5 kb EcoR1 fragment (designated R1–1) is described from a DlEPV EcoRI genomic library. This open reading frame is a homolog of the vaccinia virus rifampicin resistance (rif) gene, D13L, and encodes a putative 546 amino acid protein. The DlEPV rif contains two EcoRV, two HindIII, one XbaI, and one DraII restriction sites, and upstream of the open reading frame the fragment also contains EcoRV, HindII, SpEI, and BsP106 sites. Early poxvirus transcription termination signals (TTTTTnT) occur 236 and 315 nucleotides upstream of the consensus poxvirus late translational start codon (TAAATG) and at 169 nucleotides downstream of the translational stop codon of the rif open reading frame. Southern blot hybridization of HindIII-, EcoRI-, and BamH1-restricted DlEPV genomic DNA probed with the labeled 4.5 kb insert confirmed the fidelity of the DNA and the expected number of fragments appropriate to the restriction endonucleases used. Pairwise comparisons between DlEPV amino acids and those of the Amsacta moorei, Heliothis armigera, and Melanoplus sanguinipes entomopoxviruses, revealed 46, 46, and 45 % similarity (identity + substitutions), respectively. Similar values (41–45%) were observed in comparisons with the chordopoxviruses. The mid portion of the DlEPV sequence contained two regions of highest conserved residues similar to those reported for H. armigera entomopoxvirus rifampicin resistance protein. Phylogenetic analysis of the amino acid sequences suggested that DlEPV arose from the same ancestral node as other entomopoxviruses but belongs to a separate clade from those of the grasshopper- infecting M. sanguinipes entomopoxvirus and from the Lepidoptera-infecting (Genus B or Betaentomopoxvirus) A. moorei entomopoxvirus and H. armigera entomopoxvirus. Interestingly, the DlEPV putative protein had only 3–26.4 % similarity with RIF-like homologs/orthologs found in other large DNA non-poxviruses, demonstrating its closer relationship to the Poxviridae. DlEPV remains an unassigned member of the Entomopoxvirinae (http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/index.htm) until its relationship to other diptera-infecting (Gammaentomopoxvirus or Genus C) entomopoxviruses can be verified. The GenBank accession number for the nucleotide sequence data reported in this paper is EF541029
- …