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To investigate mandibular motion in six degrees of freedom before, during and after twin block treatment in one individual.

Shared reading is a powerful literacy intervention for the development of early communication and literacy skills. For students with extensive support needs who are beginning communicators, shared reading has the potential to support the development of initiation and expressive symbolic communication skills. This descriptive, multicase, mixed methods study investigated changes in teacher shared reading practices and perspectives, as well as the communication skills of students with extensive support needs associated with completing professional development focused on a responsive and interactive approach to shared reading. The sample included four classroom teachers and 13 students with extensive support needs in one rural U.S. public elementary school. Teachers increased their use of targeted interactive shared reading practices from 50% to 90%. Students increased the number of expressive communication skills they exhibited (p = 0.031, r = 0.60), as well as the highest level of their symbolic communication (z = 2.16, p = 0.031, r = 0.60). Thematic analysis of teacher interviews identified shifts in their perceptions of their role, expectations, and ability to support student communication development during shared reading, which converged with the changes noted from fall to spring during observations of teacher practice and students' communication skills during shared reading.

Our research constructed school life histories with 23 'lower-attaining' primary school children in England. Previous research has often failed to focus on the social justice aspects of this group, and no attempt has been made to contextualise children's misrecognition experiences within their full school life history, nor to hear primarily from children. Our results reveal for the first time the feelings, thinking and actions of lower attainers across 5 years of schooling, in response to the institutionalised practice of grouping by prior attainment. Nancy Fraser's conceptualisation of social justice as parity of participation provides our analysis framework, incorporating concepts of redistribution, recognition and representation. We focus primarily on how some low-attaining children experience misrecognition. Our results indicate how lower-attaining children sometimes identify themselves as less worthy, less connected, less similar and less visible than others. This construction allows for less respect to be shown to them and could block the fair distribution of schooling resources, and limit their opportunities for achieving social esteem.

High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.6% (42/64) of the tumors. Recurrent mutations were identified in PIK3CA, KMT2D/MLL2, K-RAS, ARID1A, NOTCH2, and RPL10. The top mutated genes included RB1, ARID1A, PTEN, KMT2D/MLL2, and WDFY3, a gene not yet implicated in NETc. Somatic CNV analysis identified two copy number gains (3q27.1 and 19q13.12) and five copy number losses (1p36.21/5q31.3/6p22.2/9q21.11/11p15.5). Also, gene fusions affecting the ACLY-CRHR1 and PVT1-MYC genes were identified in one of the eight samples subjected to RNA sequencing. To resolve evolutionary history, multiregion WES in NETc admixed with adenocarcinoma cells was performed (i.e., mixed-NETc). Phylogenetic analysis of mixed-NETc demonstrated that adenocarcinoma and neuroendocrine elements derive from a common precursor with mutations typical of adenocarcinomas. Over one-third (22/64) of NETc demonstrated a mutator phenotype of C > T at CpG consistent with deficiencies in MBD4, a member of the base excision repair (BER) pathway. Mutations in the PI3K/AMPK pathways were identified in 49/64 samples. We used two patient-derived-xenografts (PDX) (i.e., NET19 and NET21) to evaluate the activity of pan-HER (afatinib), PIK3CA (copanlisib), and ATR (elimusertib) inhibitors, alone and in combination. PDXs harboring alterations in the ERBB2/PI3K/AKT/mTOR/ATR pathway were sensitive to afatinib, copanlisib, and elimusertib (P < 0.001 vs. controls). However, combinations of copanlisib/afatinib and copanlisib/elimusertib were significantly more effective in controlling NETc tumor growth. These findings define the genetic landscape of NETc and suggest that a large subset of these highly lethal malignancies might benefit from existing targeted therapies.

Abstract Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. We demonstrate using mock samples that both enrichment methods are pan-genotypic (genotypes A-J). Using clinical samples, we demonstrate that HEP-TILE amplification successfully amplifies full genomes at the lowest HBV VL tested (30 IU/ml), and the PCR products can be sequenced using both Nanopore and Illumina platforms. Probe-based capture with Illumina sequencing required VL > 300,000 IU/ml to generate full length HBV genomes. The capture-Illumina and HEP-TILE-Nanopore pipelines had consensus sequencing accuracy of 100% in mock samples with known DNA sequences. Together, these protocols will facilitate the generation of HBV sequence data, enabling a more accurate and representative picture of HBV molecular epidemiology, cast light on persistence and pathogenesis, and enhance understanding of the outcomes of infection and its treatment.

IntroductionLes travailleurs de la santé ont fait état d’effets néfastes sur leur santé mentale dus à la pandémie de COVID-19. Nous avons exploré le profil sociodémographique des travailleurs de la santé ayant demandé par eux-mêmes à recevoir des soins de santé mentale, l’évolution des demandes de traitement au fil des vagues de COVID- 19, la nature des principaux problèmes ayant motivé les demandes et leurs changements lors de la pandémie. MéthodologieCinq grands établissements de santé de l’Ontario ont fourni du soutien en santé mentale aux travailleurs de la santé pendant la pandémie. Des données ont été recueillies à partir de 2725 demandes de traitement présentées par des travailleurs de la santé entre mai 2020 et mars 2022, à savoir la fréquence des demandes, les principaux problèmes de santé mentale ayant motivé les demandes et divers renseignements sociodémographiques (l’origine ethnique, le sexe, l’âge, le milieu de travail, la profession et l’obtention antérieure d’un diagnostic ou d’un traitement pour un problème de santé mentale). RésultatsLes travailleurs de la santé qui ont demandé à recevoir du soutien étaient en majorité des femmes et des personnes blanches. Près de la moitié d’entre eux faisaient partie du personnel infirmier. Près de la moitié avaient déjà été traités pour un problème de santé mentale et un pourcentage légèrement plus élevé avait déclaré un diagnostic antérieur de problème de santé mentale. Plus de 60 % des répondants de l’échantillon travaillaient en milieu hospitalier. Le moment des augmentations et des diminutions du nombre mensuel de nouvelles demandes coïncidait approximativement avec respectivement le début et la fin des vagues de COVID-19. Les cinq principaux problèmes à l’origine des demandes de traitement étaient les symptômes d’anxiété généralisée ou d’inquiétude, la dépression, une crise situationnelle ou une réaction aiguë à un facteur de stress, la difficulté à gérer le stress (professionnel ou financier) et des symptômes de stress post-traumatique. ConclusionDes travailleurs de la santé ont demandé par eux-mêmes à recevoir du soutien en santé mentale pendant la pandémie de COVID-19 en Ontario. La majorité d’entre eux voulaient obtenir un traitement pour des symptômes d’anxiété généralisée, d’inquiétude ou de dépression. Les résultats de cette étude pourraient éclairer la planification du réseau en vue des pandémies futures, ainsi que la planification des programmes de mieuxêtre destinés à aider le personnel de santé à faire face au stress en milieu de travail en période post-pandémique.

IntroductionHealthcare workers (HCWs) have reported COVID-19 pandemic-related adverse mental health impacts. We examined the demographic profile of HCWs who self-referred for mental health treatment, how referrals changed over time in relation to waves of COVID-19, what the main problem was for which HCWs sought treatment, and how this changed during the pandemic. MethodsFive major healthcare institutions provided mental health supports to HCWs across Ontario during the pandemic. Data from May 2020 to March 2022 were collected from 2725 HCW self-referrals regarding referral frequency, main presenting mental health problem and demographic information including ethnicity, gender, age, healthcare setting, profession and whether the HCW had a prior mental health diagnosis or had received prior mental health treatment. ResultsTreatment-seeking HCWs who self-referred predominantly self-identified as female and White. Almost half were nurses, and almost half had received previous mental health treatment; a slightly higher percentage reported a prior mental health diagnosis. Over 60% of the overall sample of HCWs worked in hospitals. The timing of increases and decreases in monthly new referrals roughly aligned with the onset and ending, respectively, of COVID-19 waves. The top five most common presenting problems for treatment-seeking were generalized anxiety/worry symptoms, depression, situational crisis/acute stress response, difficulty with stress/occupational or financial, and posttraumatic stress symptoms. ConclusionOntario HCWs self-referred to access mental health supports during the COVID-19 pandemic. The majority sought treatment for generalized anxiety/worry or depression symptoms. Results of this study may inform system planning for future pandemics, as well as for HCW wellness programs for continued workplace stress in the postpandemic period.

Abstract Rivers are often confined by structures and subjected to aggregate mining. In dynamic rivers, these interventions cause changes to riverbed and bank topography that potentially cause changes in hydraulics and flood risk. Repeat, system-scale, high-resolution topographic surveys of the gravel-bed Bislak River, the Philippines, are used to quantify annual morphological change and, using two-dimensional hydraulic modelling, to simulate changes to flood risk. Aggregate mining exports sediment and creates pitted topography, and embankments cause both deeper channels and disconnect the river from its floodplain. The consequently increased channel capacity reduces flood risk, with up to a 5% decrease in inundated areas for 10- to 100-year return periods. Sediment deprivation also increases bed shear stress that can induce scour, infrastructure damage and increased flood impacts. Rising global floodplain populations and increasing demand for aggregate ensure that sustainably managing geomorphologically dynamic rivers to support floodplain development and mitigate flood impacts remains a pertinent challenge.

Theory is an important element of literacy research. Research designs are informed by theories that explain what literacy is, how it develops, and how it should be taught and evaluated. Sociocultural theories emphasize the socially situated nature of literacies engagement and practices, whereas cognitive theories emphasize the underlying skills and processes used when reading and writing print. Research designs oriented in one of these theories are common in literacy research. Whilst some researchers have identified ways to unify across literacy theories, there is little ongoing dialogue about the ways in which a socio-cognitive orientation can contribute to literacy research. This paper discusses a student case study from a research project that gathered and analyzed data on literacy difficulties in Victoria, Australia, using both sociocultural and cognitive understandings of literacy. It uses findings from this case to explore the utility of a socio-cognitive theoretical perspective when engaging in print literacy research, proposing that it helps to identify students' loci of print literacy difficulties, recognize factors enabling and constraining literacy development, and pinpoint pedagogical elements that may require adaptation. This paper outlines broader possibilities and challenges with taking a bi-focal stance in literacy studies and invites others working across literacy paradigms to connect and share their work.

Shared reading focuses on the interaction between an adult and one or more children as they experience a book together. While research has documented classroom shared reading practices among students with diverse characteristics, few have focused on students with significant support needs. Using a conversation-analytic approach, this study sought to describe the teacher strategies that scaffolded successful interactions during shared reading in two self-contained classrooms serving students with significant support needs. Instances of teachers maximizing student participation, promoting connections with the text, maximizing multiple turn interactions, and encouraging students to take the lead were analyzed. Subsequent conversation analysis revealed that a variety of strategies supported students with significant support needs in interactions during shared reading, such as asking open ended questions, commenting, repeating and expanding student comments, modeling text-to-self connections, and providing think time. The implications for applying such strategies during shared reading with students with significant support needs are discussed.

Most teachers are not trained on how to support students who struggle with trauma. Childhood trauma not only impacts a teacher's ability to teach, but also threatens their students' futures. The purpose of this qualitative study was to investigate teachers' perceptions and actions when they participated in trauma professional development. Interviews were conducted with 5 teachers and 10 students in a Midwestern urban intermediate/middle school. By the end of the study, teachers stated that they had begun responding to disruptions in more child-centered approaches, and students noticed that their teachers began treating all students more equitably in trauma-informed manners. The implications from this study are that educating teachers on the impact of childhood trauma can change the way that teachers perceive and react to dysregulated students. Another implication is that changing teachers' beliefs, perceptions, and attitudes can be difficult if teachers retain a deficit-thinking focus.

Intron branchpoint (BP) recognition by the U2 snRNP is a critical step of splicing, vulnerable to recurrent cancer mutations and bacterial natural product inhibitors. The BP binds a conserved pocket in the SF3B1 (human) or Hsh155 (yeast) U2 snRNP protein. Amino acids that line this pocket affect the binding of splicing inhibitors like Pladienolide-B (Plad-B), such that organisms differ in their sensitivity. To study the mechanism of splicing inhibitor action in a simplified system, we modified the naturally Plad-B resistant yeast Saccharomyces cerevisiae by changing 14 amino acids in the Hsh155 BP pocket to those from human. This humanized yeast grows normally, and splicing is largely unaffected by the mutation. Splicing is inhibited within minutes after the addition of Plad-B, and different introns appear inhibited to different extents. Intron-specific inhibition differences are also observed during cotranscriptional splicing in Plad-B using single-molecule intron tracking to minimize gene-specific transcription and decay rates that cloud estimates of inhibition by standard RNA-seq. Comparison of Plad-B intron sensitivities to those of the structurally distinct inhibitor Thailanstatin-A reveals intron-specific differences in sensitivity to different compounds. This work exposes a complex relationship between the binding of different members of this class of inhibitors to the spliceosome and intron-specific rates of BP recognition and catalysis. Introns with variant BP sequences seem particularly sensitive, echoing observations from mammalian cells, where monitoring individual introns is complicated by multi-intron gene architecture and alternative splicing. The compact yeast system may hasten the characterization of splicing inhibitors, accelerating improvements in selectivity and therapeutic efficacy.

The use of exclusionary discipline (ExD) was compared for U.S. public pre-kindergarten (Pre-K) and K-12 grades within the same school. ExD rates were 10 times higher in K-12 than in Pre-K when calculated for all schools but ExD rates were comparable for schools that reported at least one case of ExD in Pre-K. Additionally, disparities in the use of ExD were observed for both Pre-K and K-12 schools: higher rates were found for boys relative to girls, for Black children relative to White children, and for charter schools relative to non-charter schools. While most schools did not use ExD, when they did, they did so at high rates. The use of ExD appears to be associated with school-level factors including a culture of use.