244 research outputs found
The Effects of Connecting Rituals on Tantrums and Physical Conflicts
This study was conducted to determine if creating strong student-teacher relationships through a program called Conscious Discipline decreased the number of physical conflicts and tantrums, therefore increasing self-regulation, in an early childhood classroom. This study took place in an early childhood Montessori classroom. There were 25 participants, mixed genders, ages 2.5 to 6 years old. The researcher taught and practiced connecting rituals from the Conscious Discipline program every day during the normal large group time. The researcher collected data by using tally marks to record every time a physical conflict, individual tantrum, or connecting ritual without adult encouragement took place, for a week before and a week after the intervention. The researcher also conducted interviews with each of the children before and after the intervention to determine if the connecting rituals created stronger relationships and feelings of safety in the classroom. The study determined that the results were not statistically significant, but the number of conflicts and tantrums decreased, and the relationship between the researcher and the students developed more fully and the feelings of safety increased. The data showed that further research is needed to examine if the length of conflicts and tantrums decrease with stronger student-teacher relationships
Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas
Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5~months), DMG-H3 (median OS: 13~months) and HAP (median OS: 8~months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5~months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time
Tetramer enrichment reveals the presence of phenotypically diverse hepatitis C virus-specific CD8+T cells in chronic infection
Virus-specific CD8+ T cells are rarely detectable ex vivo by conventional methods during chronic hepatitis C virus (HCV) infection. In this study, however, we were able to detect and characterize HCV-specific CD8+ T cells in all chronically HCV genotype 1a-infected, HLA-A*02:01-positive patients analyzed by performing major histocompatibility complex (MHC) class I tetramer enrichment. Two-thirds of these enriched HCV-specific CD8+ T-cell populations displayed an effector memory phenotype, whereas, surprisingly, one-third displayed a naive-like phenotype despite ongoing viral replication. CD8+ T cells with an effector memory phenotype could not expand in vitro, suggesting exhaustion of these cells. Interestingly, some of the naive-like CD8+ T cells proliferated vigorously upon in vitro priming, whereas others did not. These differences were linked to the corresponding viral sequences in the respective patients. Indeed, naive-like CD8+ T cells from patients with the consensus sequence in the corresponding T-cell epitope did not expand in vitro. In contrast, in patients displaying sequence variations, we were able to induce HCV-specific CD8+ T-cell proliferation, which may indicate infection with a variant virus. Collectively, these data reveal the presence of phenotypically and functionally diverse HCV-specific CD8+ T cells at very low frequencies that are detectable in all chronically infected patients despite viral persistence.
IMPORTANCE In this study, we analyzed CD8+ T-cell responses specific for HLA-A*02:01-restricted epitopes in chronically HCV-infected patients, using MHC class I tetramer enrichment. Importantly, we could detect HCV-specific CD8+ T-cell populations in all patients. To further characterize these HCV-specific CD8+ T-cell populations that are not detectable using conventional techniques, we performed phenotypic, functional, and viral sequence analyses. These data revealed different mechanisms for CD8+ T-cell failure in HCV infection, including T-cell exhaustion, viral escape, and functional impairment of naive-like HCV-specific CD8+ T cells
Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream
The subventricular zone (SVZ) provides a constant supply of new neurons to the
olfactory bulb (OB). Different studies have investigated the role of olfactory
sensory input to neural precursor cell (NPC) turnover in the SVZ but it was
not addressed if a reduced demand specifically for periglomerular neurons
impacts on NPC-traits in the rostral migratory stream (RMS). We here report
that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have
reduced complexity of the nasal turbinates, decreased sensory innervation of
the OB, reduced numbers of olfactory glomeruli and reduced OB-size without
alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved
in MT1-MMP-deficient mice, but we detected an increase in cell death-levels
and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to
controls. BrdU-tracking experiments showed that homing of NPCs specifically to
the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to
controls while numbers of tracked cells remained equal in other OB-layers
throughout all experimental groups. Altogether, our data show the demand for
olfactory interneurons in the glomerular layer modulates cell turnover in the
RMS, but has no impact on subventricular neurogenesis
Goos-Haenchen shift and localization of optical modes in deformed microcavities
Recently, an interesting phenomenon of spatial localization of optical modes
along periodic ray trajectories near avoided resonance crossings has been
observed [J. Wiersig, Phys. Rev. Lett. 97, 253901 (2006)]. For the case of a
microdisk cavity with elliptical cross section we use the Husimi function to
analyse this localization in phase space. Moreover, we present a semiclassical
explanation of this phenomenon in terms of the Goos-Haenchen shift which works
very well even deep in the wave regime. This semiclassical correction to the
ray dynamics modifies the phase space structure such that modes can localize
either on stable islands or along unstable periodic ray trajectories.Comment: 9 pages, 14 figures in reduced qualit
Immunodominance of HLA-A2-restricted hepatitis C virus-specific CD8+ T cell responses is linked to naive-precursor frequency
The impact of naïve precursor frequency on human virus-specific CD8+ T cell immunodominance is not well understood. Using a recently developed MHC class I tetramer enrichment protocol, we found a conserved hierarchy and >10-fold difference in naïve precursor frequencies across three HLA-A2 restricted HCV-specific epitopes. Importantly, the NS31406 epitope with the highest naïve precursor frequency in healthy donors was also the most frequently targeted epitope in a large cohort of chronically HCV-infected patients, both ex vivo and after in vitro stimulation. These results indicate for the first time that immunodominance in a human viral infection is linked to naïve precursor frequency
Disclinations, dislocations and continuous defects: a reappraisal
Disclinations, first observed in mesomorphic phases, are relevant to a number
of ill-ordered condensed matter media, with continuous symmetries or frustrated
order. They also appear in polycrystals at the edges of grain boundaries. They
are of limited interest in solid single crystals, where, owing to their large
elastic stresses, they mostly appear in close pairs of opposite signs. The
relaxation mechanisms associated with a disclination in its creation, motion,
change of shape, involve an interplay with continuous or quantized dislocations
and/or continuous disclinations. These are attached to the disclinations or are
akin to Nye's dislocation densities, well suited here. The notion of 'extended
Volterra process' takes these relaxation processes into account and covers
different situations where this interplay takes place. These concepts are
illustrated by applications in amorphous solids, mesomorphic phases and
frustrated media in their curved habit space. The powerful topological theory
of line defects only considers defects stable against relaxation processes
compatible with the structure considered. It can be seen as a simplified case
of the approach considered here, well suited for media of high plasticity
or/and complex structures. Topological stability cannot guarantee energetic
stability and sometimes cannot distinguish finer details of structure of
defects.Comment: 72 pages, 36 figure
Prescribed opioid use is associated with adverse cardiovascular outcomes in community-dwelling older persons
Aims: Prescribed opioids are commonly used in the older community-dwelling population for the treatment of chronic pain. Although the harmful effects of opioid abuse and overdose are well understood, little is known about the long-term cardiovascular (CV) effects of prescribed opioids. The aim of this study was to investigate the CV effects associated with prescribed opioid use. Methods and results: A post hoc analysis of participants in the Aspirin in Reducing Events in the Elderly (ASPREE) trial was conducted. Participants in the ASPREE trial included community-dwelling older adults without a prior history of CV disease (CVD). Prescribed opioid use was defined as opioid use at baseline and/or at the first annual visit (AV1). Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (95% CI) for associations between opioid use and CVD events following AV1. Of the 17 701 participants included (mean age 75.2 years, 58.2% female), 813 took opioids either at baseline or at AV1. Over a median follow-up period of 3.58 years (IQR 2.50–4.62), CVD events, most notably heart failure hospitalization, occurred in 7% (n = 57) amongst opioid users and 4% (n = 680) amongst non-opioid users. After adjustment for multiple covariates, opiate use was associated with a 1.67-fold (CI 1.26–2.23, P < 0.001) increase in the hazard ratio for CVD events. Conclusions: These findings identify opioid use as a non-traditional risk factor for CVD events in community-dwelling older adults
- …