Regularity of solutions to higher-order integrals of the calculus of variations

We obtain new regularity conditions for problems of calculus of variations with higher-order derivatives. As a corollary, we get non-occurrence of the Lavrentiev phenomenon. Our main regularity result asserts that autonomous integral functionals with a Lagrangian having coercive partial derivatives with respect to the higher-order derivatives admit only minimizers with essentially bounded derivatives

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Tactile Interactions with a Humanoid Robot : Novel Play Scenario Implementations with Children with Autism

Acknowledgments: This work has been partially supported by the European Commission under contract number FP7-231500-ROBOSKIN. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.The work presented in this paper was part of our investigation in the ROBOSKIN project. The project has developed new robot capabilities based on the tactile feedback provided by novel robotic skin, with the aim to provide cognitive mechanisms to improve human-robot interaction capabilities. This article presents two novel tactile play scenarios developed for robot-assisted play for children with autism. The play scenarios were developed against specific educational and therapeutic objectives that were discussed with teachers and therapists. These objectives were classified with reference to the ICF-CY, the International Classification of Functioning – version for Children and Youth. The article presents a detailed description of the play scenarios, and case study examples of their implementation in HRI studies with children with autism and the humanoid robot KASPAR.Peer reviewedFinal Published versio

Advice about diet and smoking for people with or at risk of age-related macular degeneration: a cross-sectional survey of eye care professionals in the UK.

BACKGROUND: In the absence of a cure, there has been considerable interest in attempts to prevent or reduce the progression of age-related macular degeneration (AMD) by targeting particular modifiable risk factors. The aim of this study was to conduct a cross-sectional survey of the current practice of UK eye care professionals in relation to advice given on diet and other lifestyle modifications for patients with or at risk of AMD. METHODS: Optometrists and ophthalmologists on the membership databases of professional organisations for the two professions were invited to participate in an online survey. The survey was open for 12 weeks between July and September 2012. RESULTS: A total of 1,468 responses were received (96.3% from optometrists and 3.7% from ophthalmologists). The response rate of those receiving the invitation was 16.2% (1,414/8735) for optometrists and 6% (54/1460) for ophthalmologists. A majority of respondents reported that they frequently provide dietary advice to patients with established AMD (67.9%) and those at risk of AMD (53.6%). Typical advice consisted of a recommendation to eat plenty of leafy green vegetables and eat more oily fish. The decision to recommend nutritional supplements was based on the risk of progression to advanced AMD, with approximately 93% of respondents recommending supplementation in a patient with advanced AMD in one eye. However for the majority, the type of supplement recommended did not comply with current best research evidence, based on the findings of the Age-related Eye Disease Study (AREDS). Only one in three optometrists regularly assessed smoking status and advised on smoking cessation. CONCLUSIONS: Within a large sample of eye care professionals, consisting predominantly of optometrists, who responded to a cross-sectional survey, there was active engagement in providing nutritional advice to patients with or at risk of AMD. However, the results demonstrate a need to raise awareness of the evidence underpinning the use of nutritional supplements together with an increased involvement in targeted smoking cessation

An endogenous small interfering RNA pathway in Drosophila

Drosophila endogenous small RNAs are categorized according to their mechanisms of biogenesis and the Argonaute protein to which they bind. MicroRNAs are a class of ubiquitously expressed RNAs of 22 nucleotides in length, which arise from structured precursors through the action of Drosha - Pasha and Dicer- 1-Loquacious complexes(1-7). These join Argonaute-1 to regulate gene expression(8,9). A second endogenous small RNA class, the Piwi-interacting RNAs, bind Piwi proteins and suppress transposons(10,11). Piwi- interacting RNAs are restricted to the gonad, and at least a subset of these arises by Piwi- catalysed cleavage of single-stranded RNAs12,13. Here we show that Drosophila generates a third small RNA class, endogenous small interfering RNAs, in both gonadal and somatic tissues. Production of these RNAs requires Dicer- 2, but a subset depends preferentially on Loquacious(1,4,5) rather than the canonical Dicer- 2 partner, R2D2 ( ref. 14). Endogenous small interfering RNAs arise both from convergent transcription units and from structured genomic loci in a tissue- specific fashion. They predominantly join Argonaute- 2 and have the capacity, as a class, to target both protein- coding genes and mobile elements. These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles

A study on the construct validity of the Parent-Child Conflict Tactics Scale (CTSPC) in an urban population in Northeast Brazil

The Parent-Child Conflict Tactics Scale (CTSPC) is one of the most widely used instruments in the world for investigating domestic violence against children, but targeted use has proven inadequate given the phenomenon's complexity. This study focused on the factor structure of CTSPC scales in an urban population in Northeast Brazil. We conducted a cross-sectional study in a cohort of 1,370 children in Salvador, Bahia State. Factor analysis with promax oblique rotation was performed, and the Kuder-Richardson coefficient was calculated. Factor analysis showed a different distribution of items in the factors as compared to the original instrument. Violence showed a gradual profile in each factor. The Kuder-Richardson coefficient was 0.63 for factor 1, 0.59 for factor 2, and 0.42 for factor 3. The items behaved differently from the original instrument, corroborating international studies. These findings support proposing a resizing of the CTSPC

HIV infection and sexual risk among men who have sex with men and women (MSMW): A systematic review and meta-analysis

Objectives: To estimate the number of men who have sex with men and women who are HIV-positive in the United States, and to compare HIV prevalence rates between men who have sex with men and women, men who have sex with men only, and men who have sex with women exclusively. Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports referencing HIV prevalence and men who have sex with men and women. We searched PubMed and Ovid PsycINFO for peer-reviewed, U.S.-based articles reporting on HIV prevalence among men who have sex with men and women. We conducted event rate, effect size, moderation and sensitivity analyses. Results: We estimate that 1.0% of U.S. males are bisexually-behaving, and that 121,800 bisexually-behaving men are HIV-positive. Men who have sex with men and women are less than half as likely to be HIV-positive as men who have sex with men only (16.9% vs. 33.3%; OR = 0.41, 95% CI: 0.31, 0.54), but more than five times as likely to be HIV-positive as men who have sex with women exclusively (18.3% vs. 3.5%; OR = 5.71, 95% CI: 3.47, 9.39). They are less likely to engage in unprotected receptive anal intercourse than men who have sex with men only (15.9% vs. 35.0%; OR = 0.36, 95% CI: 0.28, 0.46). Men who have sex with men and women in samples with high racial/ethnic minority proportions had significantly higher HIV prevalence than their counterparts in low racial/ethnic minority samples. Conclusions: This represents the first meta-analysis of HIV prevalence in the U.S. between men who have sex with men and women and men who have sex with men only. Data collection, research, and HIV prevention and care delivery specifically tailored to men who have sex with men and women are necessary to better quantify and ameliorate this population's HIV burden. © 2014 Friedman et al

Criança, violência e saúde: desafios e questões atuais

This paper examines challenges and current issues involved in measuring exposure to different types of violence which are associated mental health problems in children and adolescents. Standardized measures suitable for epidemiological studies, selected based on their relevance in the current literature, are briefly described and commented. The assessment of child's exposure to violence may focus on a specific event (e.g., kidnapping), a specific context (e.g., war) or even of a certain type of exposure (e.g., intrafamilial physical violence). The assessment of child mental health after exposure to violence has traditionally focused on posttraumatic stress disorder (PTSD) - most frequently measured through non-diagnostic scales. However, other mental health reactions may be present and screening as well as diagnostic instruments which may be used to assess these reactions are also described. Two issues of emerging importance - the assessment of impairment and of traumatic grief in children - are also presented. Availability of culturally appropriate instruments is a crucial step towards proper identification of child mental health problems after exposure to violence.Este artigo examina os desafios e perspectivas atuais envolvidos na mensuração da exposição a diferentes tipos de violência e problemas de saúde mental em crianças e adolescentes. Instrumentos padronizados apropriados para estudos epidemiológicos, selecionados com base em sua relevância na literatura, são brevemente descritos e comentados. A avaliação de exposição à violência em crianças pode dizer respeito a um evento específico (como sequestro) ou um contexto específico (como guerra) ou mesmo um determinado tipo de exposição (como violência física intrafamiliar). A avaliação da saúde mental infantil após a exposição à violência tradicionalmente concentrou-se na avaliação do transtorno de estresse pós-traumático (TEPT) - freqüentemente avaliado através de escalas não-diagnósticas. Porém, outras reações psicológicas podem ocorrer e instrumentos que podem ser usados para avaliar estas reações também são descritos neste artigo. Dois tópicos de importância emergente - a avaliação de prejuízo funcional e do pesar traumático em crianças - são também apresentados. Instrumentos culturalmente apropriados são essenciais para a identificação de problemas de saúde mental em crianças após a exposição à violência.Division of Child and Adolescent PsychiatryUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de PsiquiatriaUNIFESP, EPM, Depto. de PsiquiatriaSciEL

Significant variation in transformation frequency in Streptococcus pneumoniae

The naturally transformable bacterium Streptococcus pneumoniae is able to take up extracellular DNA and incorporate it into its genome. Maintaining natural transformation within a species requires that the benefits of transformation outweigh its costs. Although much is known about the distribution of natural transformation among bacterial species, little is known about the degree to which transformation frequencies vary within species. Here we find that there is significant variation in transformation frequency between strains of Streptococcus pneumoniae isolated from asymptomatic carriage, and that this variation is not concordant with isolate genetic relatedness. Polymorphism in the signalling system regulating competence is also not causally related to differences in transformation frequency, although this polymorphism does influence the degree of genetic admixture experienced by bacterial strains. These data suggest that bacteria can evolve new transformation frequencies over short evolutionary timescales. This facility may permit cells to balance the potential costs and benefits of transformation by regulating transformation frequency in response to environmental conditions

HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC