The history of poetry anthologies created for use in compulsory nation-state education is largely untold. As material objects, school anthologies tend to be regarded as low status and ephemeral. Yet ...these objects have a lasting impact, as they facilitate encounters that are formative in shaping public understanding of poetry. This paper illustrates how two poems that are commonly featured in school poetry anthologies, Sylvia Plath’s “You’re” and “Morning Song,” encode a historical rationale for their material form in their bibliographic practices. It shows how “You’re” and “Morning Song” became “enregistered” (Agha 190) as acceptable tokens for the discussion of motherhood and domestic relationships by school-based adolescent readers with different social valuings of poetry and different levels of literacy. The case study of these two poems illuminates how poems in their multiple versions become established within a long-lasting and pervasive pedagogical canon of poetry. As such, the multiple pedagogical versions of poems have a value in constructing a complete story of the everyday “afterlife” of a poet’s work.
Thoracic aortic aneurysm (TAA) is usually asymptomatic and associated with high mortality. Adverse clinical outcome of TAA is preventable by elective surgical repair; however, identifying at-risk ...individuals is difficult. We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status. Our goal was to identify a distinct gene expression signature in peripheral blood that may identify individuals at risk for TAA.
Whole genome gene expression profiles from 94 peripheral blood samples (collected from 58 individuals with TAA and 36 controls) were analyzed. Significance Analysis of Microarray (SAM) identified potential signature genes characterizing TAA vs. normal, ascending vs. descending TAA, and sporadic vs. familial TAA. Using a training set containing 36 TAA patients and 25 controls, a 41-gene classification model was constructed for detecting TAA status and an overall accuracy of 78+/-6% was achieved. Testing this classifier on an independent validation set containing 22 TAA samples and 11 controls yielded an overall classification accuracy of 78%. These 41 classifier genes were further validated by TaqMan real-time PCR assays. Classification based on the TaqMan data replicated the microarray results and achieved 80% classification accuracy on the testing set.
This study identified informative gene expression signatures in peripheral blood cells that can characterize TAA status and subtypes of TAA. Moreover, a 41-gene classifier based on expression signature can identify TAA patients with high accuracy. The transcriptional programs in peripheral blood leading to the identification of these markers also provide insights into the mechanism of development of aortic aneurysms and highlight potential targets for therapeutic intervention. The classifier genes identified in this study, and validated by TaqMan real-time PCR, define a set of promising potential diagnostic markers, setting the stage for a blood-based gene expression test to facilitate early detection of TAA.
Deletion of the kexin gene (KEX2) inCandida albicans has a pleiotropic effect on phenotype and virulence due partly to a defect in the expression of two major virulence factors: the secretion of ...active aspartyl proteinases and the formation of hyphae. kex2/kex2 mutants are highly attenuated in a mouse systemic infection model and persist within cultured macrophages for at least 24 h without causing damage. Pathology is modest, with little disruption of kidney matrix. The infecting mutant cells are largely confined to glomeruli, and are aberrant in morphology. The complex phenotype of the deletion mutants reflects a role for kexin in a wide range of cellular processes. Taking advantage of the specificity of Kex2p cleavage, an algorithm we developed to scan the 9168 open reading frames in Assembly 6 of theC. albicans genome identified 147 potential substrates of Kex2p. These include all previously identified substrates, including eight secreted aspartyl proteinases, the exoglucanase Xog1p, the immunodominant antigen Mp65, and the adhesin Hwp1p. Other putative Kex2p substrates identified include several adhesins, cell wall proteins, and hydrolases previously not implicated in pathogenesis. Kexins also process fungal mating pheromones; a modification of the algorithm identified a putative mating pheromone with structural similarities to Saccharomyces cerevisiaeα-factor.
To investigate the effectiveness, feasibility, and acceptability of sense of purpose (SOP) interventions in preventing or reducing anxiety or depression in youth aged 14–24 years.
A systematic search ...was conducted of the academic (PubMed/MEDLINE, PsycINFO, EMBASE) and grey literature. We also consulted two SOP experts and an Australian and Indian youth advisory group with lived experience of anxiety and/or depression. Consultations focused on the feasibility and acceptability of reviewed interventions.
The search identified 25 studies reporting on 4408 participants from six countries (64.0 % of studies in the US). Multi-component interventions targeting several SOP components (i.e., value clarification, goal setting, gratitude enhancement) reported, on average, moderate reductions in depression and anxiety symptoms in youth. Interventions were generally more effective at reducing depression than anxiety symptoms. In terms of sub-populations or groups, there was some evidence for greater intervention effectiveness among youth with prior therapy experience, extraverted personalities, and those with already elevated anxiety/depression symptoms. Youth advisors and experts opined that group interventions were most acceptable to young people.
This review was limited to a recent 10-year timeframe and publications in English, potentially excluding relevant studies published prior to 2011 or in other languages.
Fostering SOP can lead to better psychological wellbeing in youth. Potential harms resulting from interventions can occur without adequate consideration for a person's readiness for purpose discovery, environmental barriers, and familial and cultural settings. Further research in more diverse populations is required to determine who benefits and in what contexts.
•Fostering purpose can promote psychological wellbeing in young people.•Multicomponent, group-based interventions were most effective and accepted overall.•Interventions more effective at reducing depression rather than anxiety symptoms.•Mainly Caucasian females in high-income countries. More diverse samples needed.•Potential harms can occur without considering one's readiness for purpose discovery.
Objective
To identify motivation, capabilities and opportunities that enable psychiatrists and registrars to seek help for mental health problems and to inform design of interventions.
Method
Data ...collected in qualitative semi-structured interviews were analysed using a framework approach with the COM-B model of behaviour as a theoretical frame.
Results
Accounts of the eight participants show help-seeking to be a complex process requiring cognitive and emotional capability to recognise a problem or goal, acceptance of vulnerability, and facilitated by access to professional networks. Help-seeking was enabled by openness about mental health problems in workplace culture.
Conclusions
Interventions to enable help-seeking should focus on normalising the experience of mental health problems among doctors and challenge the notion that difficulties represent characterological flaws. Greater understanding of the mandatory reporting requirements is also required.
Abstract Background Satisfying close relationships are associated with higher levels of life satisfaction throughout the life course. Despite the fundamental role of attachment style in close ...relationships, few studies have longitudinally examined the association between attachment style in young adults with later life satisfaction. Method Data from 2,088 participants in a longitudinal birth cohort study were examined. At 21-years, participants completed the Attachment Style Questionnaire which comprises five domains reflective of internal working models of interpersonal relationships and attachment style: confidence (security), discomfort with closeness and relationships as secondary (avoidance), need for approval and preoccupation with relationships (anxiety). At 30-years, participants self-reported their overall life satisfaction. Linear regression was used to longitudinally examine the association between attachment domains at 21-years and life satisfaction at age 30. Results After adjustments, confidence was positively associated with life satisfaction (β = 0.41, 95% CI 0.25–0.56, p < 0.001), while need for approval was negatively associated with life satisfaction (β = -0.17, 95% CI -0.30 – -0.04, p < 0.001). Low income at 21, caring for a child by age 21, and leaving the parental home at 16-years or under were negatively associated with life satisfaction at 30-years. Conclusion Young adult attachment style is associated with later life satisfaction, particularly through confidence in self and others. Promoting positive internal working models of interpersonal relationships and fostering greater confidence in self and others in adolescence may be an effective strategy for improving life satisfaction later in life.
This paper presents the results of a textual and linguistic analysis of characters' speech patterns and discusses the racial and cultural implications of the ways in which dialects are represented in ...the novel The Help by Kathyrn Stockett. The linguistic stigmatization of the black characters in Stockett's novel needs to be viewed as something much larger than a reflection of a single author's individual prejudices, but rather, as a popular-culture indication of the racial and class anxieties that are deeply woven into the sociocultural fabric of American society, a society that embraces and popularizes such linguistic choices.
Introduction: Current therapies for patients with acute myeloid leukemia (AML) push the limits of chemotherapy intensity but cure only 30% of adults and 70% of children. Recently developed ...antibody-based therapies and molecularly-targeted agents only modestly improve outcomes for select patient subsets. Thus, new approaches are needed. Given the success of chimeric antigen receptor (CAR) T-cell therapies for acute lymphoblastic leukemia (ALL), we developed and optimized a novel CD33 CAR T-cell (CD33CART) construct for clinical testing in a multicenter Phase I/II clinical trial in children, adolescents, and young adults (AYA) with relapsed/refractory (r/r) AML. ( Qin H, et al. JITC 2021) We report interim results following completion of the dose-escalation phase. Methods: This multicenter phase I/II clinical trial (NCT03971799) was conducted as a 3+3 dose escalation study through the Pediatric Transplantation and Cell Therapy Consortium with National Marrow Donor Program sponsorship and managed by CIBMTR CRO. Autologous CD33CART product were centrally manufactured on a ClinicMACS Prodigy® by the Biopharmaceutical Development Program at the Frederick National Laboratory for Cancer Research (NCI). Eligibility criteria were r/r AML in subjects < 35 years old with adequate organ/performance status and an identified allogeneic stem cell transplant (SCT) donor. Bone marrow assessment was used for standard morphologic evaluation and central flow cytometric minimal residual disease (MRD) quantification. All subjects received pre-CD33CART lymphodepleting chemotherapy (LD) with fludarabine (75-120 mg/m 2) and cyclophosphamide (900-1000 mg/m 2). CD33CART doses levels (DLs) were: DL1: 3 x 10 5 CD33 CAR+ T-cells/kg; DL2: 1 x 10 6/kg; DL3: 3 x 10 6/kg and DL4: 1 x 10 7/kg. Adverse event grading used CTCAE v5 with incorporation of ASTCT consensus definitions for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Dose-limiting toxicities (DLTs) included > grade 3 CRS, > grade 3 ICANS, and persistent > grade 3 non-hematologic toxicity that did not resolve < grade 2 in 72 hours. CD33CART persistence was assessed via flow cytometric evaluation of the blood and bone marrow. Data cut-off was June 1, 2023. Results: A total of 24 subjects (median age of 16 years, range 1-34 years), were enrolled, 12 (50%) of whom underwent a prior SCT. CD33CART products were successfully manufactured for 23 subjects and infused into 19. In 4 non-infused subjects with manufactured products, 1 died from progressive disease (PD) prior to LD, 2 transitioned to palliative care and 1 withdrew consent to seek alternative therapy. Manufacturing was not performed in one subject due to death from PD after enrollment. One morbidly obese subject (BMI=49.3) enrolled at DL4 but received treatment at DL3 due to weight-based manufacturing limitations. The median time from enrollment to infusion was 47 days (range, 24-242). (Table) Three subjects each were infused at DL1 and DL2 without DLTs. At DL3, 1 subject experienced DLT (grade 4 CRS) prompting expansion at this dose level, and no subsequent DLTs were observed. At DL4, 1 subject experienced a prolonged grade 3 CRS (> 72 hours) and grade 3 ICANS, both constituting DLT and necessitating expansion of the cohort without additional DLTs seen. Across all dose-levels, CRS was seen in 13 (68%) patients and was > grade 3 in 4 (21%) with onset typically within the first 24 hours post-infusion. Complete remission (CR) was only seen at DL4 and achieved in 2 subjects, both achieving an MRD negative CR alongside myeloid aplasia. One SCT naïve subject developed candidemia during aplasia but was able to proceed to an allogenic SCT, achieved engraftment, and was in remission at Day +100 post SCT. The second patient (post-two prior SCTs) declined third SCT, had spontaneous count recovery and remained in remission until day +119 (MRD+ relapse). Transient CD33CART expansion was detected in 9 (47.4%) subjects overall and in all 6 (100%) subjects at DL4. Conclusions: CD33CART manufacturing is feasible in children and AYAs with r/r AML with acceptable toxicity experienced in treated subjects. CD33CART expansion was best in subjects treated at DL4 (1 x 10 7/kg) with MRD negative CRs and transient myeloid aplasia occurring in 2 of 5 (40%) subjects evaluable for response (Table). Based on early clinical efficacy at DL4, enrollment continues in the phase 2 portion.
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