202 research outputs found

    Examining the Factor Structure of Therapist Fidelity in First-Episode Psychosis Intervention: Relationships with Baseline Client and Clinician Characteristics during Individual Resiliency Training

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    Evidence-based approaches and early intervention have improved the long-term prognosis of individuals with schizophrenia. However, little is known about the therapeutic processes involved in individual therapy in first-episode psychosis. A comprehensive psychosocial/psychiatric program for this population, NAVIGATE, includes an individual therapy component, Individual Resiliency Training (IRT). Fidelity of clinicians’ adherence to the IRT protocol has been collected to ensure proper implementation of this manual-based intervention. These data can provide insight into the elements of the therapeutic process in this intervention. To achieve this goal, I first examined the factor structure of the IRT fidelity scale with exploratory factor analysis. Secondly, I explored the relationships of the IRT fidelity ratings (and any derived factors) with clinician years of experience and years of education, and client’s baseline symptom severity and duration of untreated psychosis. Results supported a two-factor structure of the IRT fidelity scale. Correlations between clinician years of education and fidelity ratings were statistically significant.Bachelor of Art

    Continental slope and rise geomorphology seaward of the Totten Glacier, East Antarctica (112°E-122°E)

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    The continental slope and rise seaward of the Totten Glacier and the Sabrina Coast, East Antarctica features continental margin depositional systems with high sediment input and consistent along-slope current activity. Understanding their genesis is a necessary step in interpreting the paleoenvironmental records they contain. Geomorphic mapping using a systematic multibeam survey shows variations in the roles of downslope and along slope sediment transport influenced by broad-scale topography and oceanography. The study area contains two areas with distinct geomorphology. Canyons in the eastern part of the area have concave thalwegs, are linked to the shelf edge and upper slope and show signs of erosion and deposition along their beds suggesting cycles of activity controlled by climate cycles. Ridges between these canyons are asymmetric with crests close to the west bank of adjacent canyons and are mostly formed by westward advection of fine sediment lofted from turbidity currents and deposition of hemipelagic sediment. They can be thought of as giant levee deposits. The ridges in the western part of the area have more gently sloping eastern flanks and rise to shallower depths than those in the east. The major canyon in the western part of the area is unusual in having a convex thalweg; it is likely fed predominantly by mass movement from the flanks of the adjacent ridges with less sediment input from the shelf edge. The western ridges formed by accretion of suspended sediment moving along the margin as a broad plume in response to local oceanography supplemented with detritus originating from the Totten Glacier. This contrasts with interpretations of similar ridges described from other parts of Antarctica which emphasise sediment input from canyons immediately up-current. The overall geomorphology of the Sabrina Coast slope is part of a continuum of mixed contourite-turbidite systems identified on glaciated margins.Australian Government 4333Australian Research Council DP170100557Italian Programma Nazionale di Richerch in Antartide (PNRA)Spanish Government CTM2014-60451-C2-1-P CTM2017-89711-C2-1-

    Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles

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    To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT), indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER) and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER

    An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

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    : Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Recent Salmon Declines: A Result of Lost Feeding Opportunities Due to Bad Timing?

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    As the timing of spring productivity blooms in near-shore areas advances due to warming trends in global climate, the selection pressures on out-migrating salmon smolts are shifting. Species and stocks that leave natal streams earlier may be favoured over later-migrating fish. The low post-release survival of hatchery fish during recent years may be in part due to static release times that do not take the timing of plankton blooms into account. This study examined the effects of release time on the migratory behaviour and survival of wild and hatchery-reared coho salmon (Oncorhynchus kisutch) using acoustic and coded-wire telemetry. Plankton monitoring and near-shore seining were also conducted to determine which habitat and food sources were favoured. Acoustic tags (n = 140) and coded-wire tags (n = 266,692) were implanted into coho salmon smolts at the Seymour and Quinsam Rivers, in British Columbia, Canada. Differences between wild and hatchery fish, and early and late releases were examined during the entire lifecycle. Physiological sampling was also carried out on 30 fish from each release group. The smolt-to-adult survival of coho salmon released during periods of high marine productivity was 1.5- to 3-fold greater than those released both before and after, and the fish's degree of smoltification affected their downstream migration time and duration of stay in the estuary. Therefore, hatchery managers should consider having smolts fully developed and ready for release during the peak of the near-shore plankton blooms. Monitoring chlorophyll a levels and water temperature early in the spring could provide a forecast of the timing of these blooms, giving hatcheries time to adjust their release schedule

    The fitness cost of mis-splicing is the main determinant of alternative splicing patterns

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    Background Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated. Results We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92–98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. Conclusions These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift

    Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

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    Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms

    Prácticas docentes para creatividad en la universidad: estudio en Portugal y Brasil

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    Creativity is nowadays seen as an essential feature in higher education. Nevertheless, there is a discrepancy between the need for creativity and what higher education classrooms provide. This study assessed the perceptions of 1599 higher education students from two countries (1059 Brazilian and 540 Portuguese students), from two academic domains (Sciences and Technologies – Sc&T; Social Sciences, Arts, and Humanities – SScA&H), about the presence of creativity in their teachers’ instruction and evaluation practices. The study’s findings evidence interactive effects between the variables country and academic domain for most of the assessed factors: encouragement of new ideas, climate for the expression of ideas, and interest in students’ learning. Brazilian Sc&T students presented more negative perceptions of their classroom environments when compared to SScA&H students; Portuguese students showed opposite patterns of results. Some hypothetical explanations are discussed and future directions for research are presented.Criatividade é atualmente tomada como aspecto essencial na Educação Superior. Há, contudo, discrepância entre a necessidade de criatividade e o que a universidade proporciona. Este estudo avaliou percepções de 1599 alunos universitários de dois países (1059 brasileiros e 540 portugueses), de duas áreas curriculares (Ciências e Tecnologias – Sc&T; Ciências Sociais, Artes e Humanidades – SscA&H) sobre a presença de criatividade nas práticas docentes, instrucionais e avaliativas, de que são alvo. Os resultados mostraram efeitos interativos significativos entre as variáveis país e área curricular para a maioria dos fatores avaliados: encorajamento de novas ideias, clima para expressão de ideias e interesse pela aprendizagem dos alunos. Os estudantes brasileiros de Sc&T mostraram percepções mais negativas da sala de aula, comparados com os de SScA&H; os alunos portugueses obtiveram padrões opostos nos resultados. Algumas hipóteses explicativas são discutidas e são apresentadas orientações para pesquisa futura.La creatividad está actualmente considerada como aspecto esencial en la Educación Superior. Sin embargo, existe discrepancia entre la necesidad de creatividad y lo que la universidad ofrece. Este estudio evaluó percepciones de 1.599 estudiantes universitarios (1.059 de Brasil y 540 de Portugal) de dos áreas curriculares (Ciencia y Tecnología – Sc&T; Ciencias Sociales, Artes y Humanidades – SscA&T) acerca de la presencia de creatividad en las prácticas docentes, instructivas y evaluativas dirigidas a ellos. Los resultados mostraron efectos de interacción significativos entre las variables país y área curricular para la mayoría de los factores evaluados: fomento de nuevas ideas, entorno para la expresión de ideas e interés en el aprendizaje del estudiante. Los estudiantes brasileños de Sc&T mostraron percepciones más negativas de la clase en comparación con los de SSCA&H; los estudiantes portugueses obtuvieron patrones opuestos en los resultados. Algunas hipótesis explicativas se discuten y se presentan directrices para investigación futura.Thermo Scientificinfo:eu-repo/semantics/publishedVersio
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