Anisotropically Inflating Universes

We show that in theories of gravity that add quadratic curvature invariants to the Einstein-Hilbert action there exist expanding vacuum cosmologies with positive cosmological constant which do not approach the de Sitter universe. Exact solutions are found which inflate anisotropically. This behaviour is driven by the Ricci curvature invariant and has no counterpart in the general relativistic limit. These examples show that the cosmic no-hair theorem does not hold in these higher-order extensions of general relativity and raises new questions about the ubiquity of inflation in the very early universe and the thermodynamics of gravitational fields.Comment: 5 pages, further discussion and references adde

Répercussions d’une enfance vécue en institution : le cas des Enfants de Duplessis

Les conséquences négatives d’un placement en institution sur les enfants ont été documentées, mais aucune étude n’a porté sur les orphelins et les enfants placés une fois devenus adultes. Au Québec, les Enfants de Duplessis offrent un témoignage poignant des répercussions à long terme d’une enfance vécue en institution. Les histoires recueillies auprès de 40 hommes et 41 femmes ayant grandi en institution à l’époque de Duplessis font état d’un nombre élevé d’abus et d’expériences adverses, incluant les agressions physiques, psychologiques et sexuelles. Le milieu était peu stimulant et offrait peu d’opportunités de développer des relations d’attachement positives et significatives. Lorsqu’ils sont appariés et comparés à des adultes provenant de l’enquête Santé-Québec, les Enfants de Duplessis devenus adultes rapportent plus de problèmes de santé liés au stress et une détresse psychologique plus importante. Nos résultats indiquent également que les personnes ayant disposé de peu de ressources et d’aptitudes personnelles dans l’enfance sont les plus affectées par les expériences adverses.Whereas the immediate consequences of institutionalized placements on children have been documented, no study has investigated adults who were raised in orphanages or institutions. In Quebec, les enfants de Duplessis offer a unique testimony of the long term consequences of an institutionalized childhood. Stories collected from 40 men and 41 women who grew up in institution in Duplessis’era indicate a high number of abuse and aversive experiences, including physical, psychological and sexual aggressions. In addition, the environment was poor in stimulation and opportunities to develop positive attachment relationships with adults. When matched and compared to adults from the Santé-Québec survey, les enfants de Duplessis report a higher number of health problems associated with stress and more psychological distress. Moreover, our results indicate that those who had fewer strengths and aptitudes in childhood are the most affected by unfavourable experiences.Se han documentado las consecuencias negativas del ingreso de los niños a una institución, pero ningún estudio trata acerca de los adultos que fueron internados cuando eran niños o quedaron huérfanos. En Quebec los niños de Duplessis son un testimonio desgarrador de las repercusiones a largo plazo de una infancia vivida en una institución. Las historias recopiladas de 40 hombres y 41 mujeres que crecieron en una institución en la época de Duplessis constatan el número elevado de abusos y experiencias adversas, incluyendo agresiones físicas, psicológicas y sexuales. El medio era poco estimulante y ofrecía pocas oportunidades de desarrollar relaciones de apego positivas y significativas. Al emparejarlos y compararlos a los adultos provenientes de la encuesta de Salud Quebec, los niños de Duplessis, quienes ya son adultos, reportan más problemas de salud relacionados al estrés y un desasosiego psicológico más importante. Nuestros resultados indican también que las personas que disponen de pocos recursos y aptitudes personales en su infancia son las más afectadas por las experiencias adversas.As conseqüências negativas de uma internação em instituição sobre as crianças foram documentadas, mas nenhum estudo foi realizado sobre os órfãos e as crianças internadas quando já se tornaram adultas. No Quebec, as “crianças de Duplessis” testemunham de maneira profunda das repercussões a longo prazo de uma infância vivida em instituição. As histórias recolhidas junto a 40 homens e 41 mulheres que cresceram em instituição na época do governo de Duplessis relatam um alto número de abusos e de experiências adversas, incluindo agressões físicas, psicológicas e sexuais. O meio era pouco estimulante e oferecia poucas oportunidades de desenvolver relações de apego positivas e significativas. Quando eles foram colocados lado a lado e comparados aos adultos vindos da pesquisa de Santé-Québec, as “crianças de Duplessis” que se tornaram adultas sofrem mais de problemas de saúde ligados ao estresse e a uma depressão psicológica mais importante. Nossos resultados indicam igualmente que as pessoas que dispuseram de poucos recursos e aptidões pessoais na infância são mais afetadas pelas experiências adversas

Les expériences vécues par les enfants de Duplessis institutionnalisés : les conséquences après plus de 50 ans

Dans cet article, les auteurs présentent les résultats qualitatifs recueillis à partir de questionnaires et d’entrevues semi-structurées destinés à documenter les expériences tant actuelles que passées des enfants de Duplessis institutionnalisés (EDI). Des exemples typiques et deux cas représentatifs sont présentés. Les résultats indiquent que les abus et la négligence subis par les EDI pendant l’enfance ont compromis leur ajustement psychosocial à long terme. Ils révèlent aussi que les EDI qui ont rapporté au moins quatre forces pendant leur enfance étaient plus susceptibles d’être protégés à l’âge adulte contre les effets négatifs de leur placement.In this article, the authors present qualitative results, derived from questionnaires and semi-structured interviews, to describe past and present experiences of the Duplessis children. Examples representative of their experience and a detailed description of two cases are provided. Results indicate that childhood abuse and negligence are related to poorer long-term psychological adjustment. The findings also demonstrate that reporting at least four strengths in childhood can have long-term protective effects.En este artículo, los autores presentan los resultados cualitativos recopilados a partir de cuestionarios y entrevistas semiestructuradas destinadas a documentar las experiencias, tanto recientes como pasadas, de los niños de Duplessis que fueron institucionalizados (EDI). Se presentan ejemplos típicos y dos casos representativos. Los resultados indican que los abusos y la negligencia sufridos por los EDI durante la infancia han comprometido su ajuste psicosocial a largo plazo. También revelan que los EDI que han reportado al menos cuatro fuerzas durante su infancia eran más susceptibles de estar protegidos en la edad adulta contra los efectos negativos de su colocación.Neste artigo, os autores apresentam os resultados qualitativos coletados a partir de questionários e entrevistas semi-estruturadas destinados a documentar as experiências tanto atuais quanto passadas das crianças de Duplessis institucionalizadas (CDI). São apresentados exemplos típicos e dois casos representativos. Os resultados indicam que os abusos e a negligência sofridos pelas CDI durante a infância comprometeram seu ajuste psicossocial a longo prazo. Eles revelam também que as CDI que relataram, pelo menos, quatro aspectos positivos durante sua infância eram mais susceptíveis de ser protegidas durante a idade adulta contra os efeitos negativos de sua internação

Dynamic Field Experiments in Development Economics: Risk Valuation in Morocco, Kenya, and Peru

The effective design and implementation of interventions that reduce vulnerability and poverty require a solid understanding of underlying poverty dynamics and associated behavioral responses. Stochastic and dynamic benefit streams can make it difficult for the poor to learn the value of such interventions to them. We explore how dynamic field experiments can help (i) intended beneficiaries to learn and understand these complicated benefit streams, and (ii) researchers to better understand how the poor respond to risk when faced with nonlinear welfare dynamics. We discuss and analyze dynamic risk valuation experiments in Morocco, Peru, and Kenya.poverty, risk and uncertainty, dynamics, experiments, Kenya, Morocco, Peru, International Development, Research Methods/ Statistical Methods, Risk and Uncertainty,

Transduction of Non-Small Cell Lung Cancer Cells by Adenoviral and Retroviral Vectors

Gene transfer into a panel of non-small cell lung cancer (NSCLC) cells by adenoviral (Ad) and retroviral (RV) vectors was studied. Indexed to multiplicity of infection (MOI), Ad vectors transduce squamous, adenosquamous, and malignant mesothelioma cells with greater efficiency than large cells or adenocarcinoma cells. Transduction-sensitive cells bind the Ad vector with specificity for the Ad fiber knob, and internalize vector efficiently. Transduction-refractory cells bind and internalize vector by less efficient pathways. Like Ad vectors, there is heterogeneity in RV transduction efficiencies of different NSCLC subtypes. With respect to the most common cell type metastatic to the pleural space (adenocarcinoma), amphotropic retroviral vectors transduce cells of this subtype more efficiently (at a lower MOI) than Ad. RV transduction is not solely dependent on cellular replication, and both permissive and refractory cell lines express the mRNA for the amphotropic RV receptor. These observations suggest that neither Ad nor RV vectors will suffice a priori as the optimal gene transfer vehicle, and successful gene therapy of lung cancer may require tumor-specific or patient-specific vectors

The Contribution of Accessory Toxins of Vibrio cholerae O1 El Tor to the Proinflammatory Response in a Murine Pulmonary Cholera Model

The contribution of accessory toxins to the acute inflammatory response to Vibrio cholerae was assessed in a murine pulmonary model. Intranasal administration of an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe pathology and decreased serum levels of proinflammatory molecules interleukin (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest that the RTX toxin contributes to the severity of acute inflammatory responses. Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin (hlyA) did not significantly affect virulence in this model. Compound deletion of ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but induced pulmonary disease with limited inflammation and significantly reduced serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive, compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins

Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson's Disease: The ICICLE-PD Study.

BACKGROUND: Cognitive decline is a frequent complication of Parkinson's disease (PD) and the identification of predictive biomarkers for it would help in its management. OBJECTIVE: Our aim was to analyse whether senescence markers (telomere length, p16 and p21) or their change over time could help to better predict cognitive and motor progression of newly diagnosed PD patients. We also compared these senescence markers to previously analysed markers of inflammation for the same purpose. METHODS: This study examined the association of blood-derived markers of cell senescence and inflammation with motor and cognitive function over time in an incident PD cohort (the ICICLE-PD study). Participants (154 newly diagnosed PD patients and 99 controls) underwent physical and cognitive assessments over 36 months of follow up. Mean leukocyte telomere length and the expression of senescence markers p21 and p16 were measured at two time points (baseline and 18 months). Additionally, we selected five inflammatory markers from existing baseline data. RESULTS: We found that PD patients had shorter telomeres at baseline and 18 months compared to age-matched healthy controls which also correlated to dementia at 36 months. Baseline p16 levels were associated with faster rates of motor and cognitive decline over 36 months in PD cases, while a simple inflammatory summary score at baseline best predicted cognitive score over this same time period in PD patients. CONCLUSION: Our study suggests that both inflammatory and senescence markers (p16) are valuable predictors of clinical progression in PD patients.This study was supported by a Newcastle upon Tyne Hospital Trust (Brain Research Unit PD0612) grant to GS. ICICLE-PD is funded by Parkinson’s UK (grant no J-0802, G-1301) and supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre in Ageing and Chronic Disease and the Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University (CM-R) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (146281). This work was also supported by grants from the Academy of Medical Sciences, UK, the Rosetrees Trust, and the Stevenage Biosciences Catalyst. CHWG is supported by a RCUK/UKRI Research Innovation Fellowship awarded by the Medical Research Council (MR/R007446/1). RAB is an NIHR Senior Investigator (NF-SI-0616-10011) and is supported by the WT/MRC Stem Cell Institute (203151/Z/16/Z

A Phylogenomic Study of the Genus Alphavirus Employing Whole Genome Comparison

The phylogenetics of the genus Alphavirus have historically been characterized using partial gene, single gene or partial proteomic data. We have mined cDNA and amino acid sequences from GenBank for all fully sequenced and some partially sequenced alphaviruses and generated phylogenomic analyses of the genus Alphavirus genus, employing capsid encoding structural regions, non-structural coding regions and complete viral genomes. Our studies support the presence of the previously reported recombination event that produced the Western Equine Encephalitis clade, and confirm many of the patterns of geographic radiation and divergence of the multiple species. Our data suggest that the Salmon Pancreatic Disease Virus and Sleeping Disease Virus are sufficiently divergent to form a separate clade from the other alphaviruses. Also, unlike previously reported studies employing limited sequence data for correlation of phylogeny, our results indicate that the Barmah Forest Virus and Middelburg Virus appear to be members of the Semliki Forest clade. Additionally, our analysis indicates that the Southern Elephant Seal Virus is part of the Semliki Forest clade, although still phylogenetically distant from all known members of the genus Alphavirus. Finally, we demonstrate that the whole Rubella viral genome provides an ideal outgroup for phylogenomic studies of the genus Alphavirus

Brief Report: The Role of Task Support in the Spatial and Temporal Source Memory of Adults with Autism Spectrum Disorder

Adults with autism spectrum disorder (ASD) show intact recognition (supported procedure) but impaired recall (unsupported procedure) of incidentally-encoded context. Because this has not been demonstrated for temporal source, we compared the temporal and spatial source memory of adults with ASD and verbally matched typical adults. Because of difficulties with temporal processing in ASD, we predicted ASD adults would benefit from test support for location but not temporal occurrence of studied words. We found similar levels of recognition and source memory for both groups but there was a greater effect of support on memory for location source in the ASD group. The lack of an effect of support for temporal source may simply reflect a difficulty in operationalising temporal cues

H1N1 2009 Pandemic Influenza Virus: Resistance of the I223R Neuraminidase Mutant Explained by Kinetic and Structural Analysis

Two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that antiviral resistant viruses emerge and spread in the human population. The 2009 pandemic H1N1 virus is already resistant to adamantanes. Recently, a novel neuraminidase inhibitor resistance mutation I223R was identified in the neuraminidase of this subtype. To understand the resistance mechanism of this mutation, the enzymatic properties of the I223R mutant, together with the most frequently observed resistance mutation, H275Y, and the double mutant I223R/H275Y were compared. Relative to wild type, KMvalues for MUNANA increased only 2-fold for the single I223R mutant and up to 8-fold for the double mutant. Oseltamivir inhibition constants (KI) increased 48-fold in the single I223R mutant and 7500-fold in the double mutant. In both cases the change was largely accounted for by an increased dissociation rate constant for oseltamivir, but the inhibition constants for zanamivir were less increased. We have used X-ray crystallography to better understand the effect of mutation I223R on drug binding. We find that there is shrinkage of a hydrophobic pocket in the active site as a result of the I223R change. Furthermore, R223 interacts with S247 which changes the rotamer it adopts and, consequently, binding of the pentoxyl substituent of oseltamivir is not as favorable as in the wild type. However, the polar glycerol substituent present in zanamivir, which mimics the natural substrate, is accommodate