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National policy in England recommends that young people be admitted to mental health wards that are age-appropriate. Despite this, young people continue to be admitted to adult wards.
Aims
To explore the impact of young people’s admissions to adult wards, from the perspectives of young people, parents/carers and mental health professionals working in adult services.
Method
Semi-structured interviews were conducted with 29 participants to explore experiences of receiving and delivering care in adult mental health wards. Participants were four young people (aged 16–17 years), four parents/carers and 21 mental health professionals from adult mental health services in England. Data were analysed using framework analysis.
Results
Young people’s admissions to adult wards tend to occur out of hours, at a time of crisis and when no suitable adolescent bed is available. Admissions were conceptualised as a short-term safety measure rather than for any therapeutic input. Concerns were raised about safeguarding, limited treatment options and a lack of education provision for young people on adult wards. However, exceptionally, for older adolescents, an adult ward might be clinically or socially appropriate. Recommendations to reduce adult ward admissions included better integration of adolescent and adult services, having more flexible policies and increasing community provision.
Conclusions
Our findings emphasise the importance of young people being admitted to age-appropriate in-patient facilities. Earlier intervention and increased provision of specialist care in the community could prevent young people’s admissions to adult wards.
The high level of psychological distress in young people is a growing concern. However, there are few national surveys that describe the trajectories of mental health and wellbeing through adolescence into early adulthood. Further, existing research has largely focused exclusively on mental ill-health, with little focus on positive mental health. This study provides the first national profile of the mental health and wellbeing of Australians aged 12–25 years.
Methods
Participants completed the National Youth Mental Health survey in 2018 (n1 = 3832), 2020 (n2 = 974) or 2022 (n3 = 961). We applied Keyes’ Complete Mental Health (CMH) framework to derive categories of mental health and wellbeing, and examine rates of CMH over time, by age and gender.
Results
While approximately half of those surveyed reported flourishing (high wellbeing without mental illness), rates of flourishing declined between 2018 and 2022. Rates of flourishing generally decreased with age, and flourishing was more prevalent amongst males than females.
Conclusions
The findings provide a unique contrast of youth mental health pre-, during and post- the COVID-19 pandemic. While rates of psychological distress are consistently high, the proportion of youth reporting flourishing highlights the need to consider all aspects of psychological functioning to accurately understand and respond to the mental health needs of young people.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.
This comprehensive collection is an essential resource for teacher educators, teachers and educational researchers. Prominent researchers and authors in ELT, as well as newer scholars, have contributed chapters on key issues of the day.Topics such as language teacher education by distance; technology and SLTE; assessment in SLTE; standards and SLTE, and teacher preparation and non-native English-speaking educators address the changing contexts of language teaching and teacher education today.
Written by internationally prominent researchers, educators, and emerging scholars, the chapters are grouped into five sections: rethinking our understanding of teaching, learner diversity and classroom learning, pedagogical approaches and practices, components of the curriculum, and media and materials. Each chapter covers key topics in teaching methodology such as reflective pedagogy, teaching large classes, outcomes-based language learning, speaking instruction, and technology in the classroom. Chapters assume no particular background knowledge and are written in an accessible style.
The Cambridge Guide to Learning English as a Second Language contains nine sections, which aim to organise and reflect different dimensions of the diverse and complex scope of learning English as a second or additional language. Four themes which permeate the chapters are: learning and learners; learning and language; learning and language development; learning and learning context. The 36 authoritative chapters are written by experts in the field. It is accessibly written and appropriate for students in undergraduate and mainstream graduate TESOL courses as well as teacher educators wishing to link issues of learning with classroom pedagogy.
We investigate a recent proposal for modal hypersequent calculi. The interpretation of relational hypersequents incorporates an accessibility relation along the hypersequent. These systems give the same interpretation of hypersequents as Lellman’s linear nested sequents, but were developed independently by Restall for S5 and extended to other normal modal logics by Parisi. The resulting systems obey Došen’s principle: the modal rules are the same across different modal logics. Different modal systems only differ in the presence or absence of external structural rules. With the exception of S5, the systems are modular in the sense that different structural rules capture different properties of the accessibility relation. We provide the first direct semantical cut-free completeness proofs for K, T, and D, and show how this method fails in the case of B and S4.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
Aims
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
Method
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
Results
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Conclusions
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
The apolipoprotein E ε4 allele (APOE*ε4) is indicated as a risk for Alzheimer's disease and other age-related diseases. The risk attributable to APOE*ε4 for depression is less clear and may be because of confounding of the relationship between dementia and depression.
Aims
We examined the risk of APOE* ε4 for incident depression and depressive symptomology over a 12-year period across the adult lifespan.
Method
Participants were from the Personality and Total Health Through Life study, aged 20 to 24 (n = 1420), 40 to 44 (n = 1592) or 60–64 (n = 1768) at baseline, and interviewed every 4 years since 1999. Ethnicities other than White, those without genotyping and those with depression at baseline, or who reported strokes and scores on the Mini-Mental State Examination <27 at any observation, were excluded.
Results
Over the study period, there was no evidence that APOE*ε4+ was a risk factor for depression, including any depression (odds ratio (OR) = 0.94, 95% CI 0.77–1.16, P = 0.573), major depression (OR = 0.96, 95% CI 0.60–1.53, P = 0.860), minor depression (OR = 0.94, 95% CI 0.67–1.30, P = 0.695) or depressive symptomology (incidence rate ratio (IRR) = 1.02, 95% CI 0.97–1.08, P = 0.451). APOE*ε4 was unrelated to incident depression. Findings were consistent for all age cohorts.
Conclusions
Among cognitively intact Australian adults who were free of depression at baseline, there was little evidence that APOE*ε4+ carriers are at increased risk for depression over a 12-year period among those who are cognitively intact.
In this contribution, we use heavy ion irradiation and photoluminescence (PL) spectroscopy to demonstrate that defects can be used to tailor the optical properties of two-dimensional molybdenum disulfide (MoS2). Sonicated MoS2 flakes were deposited onto Si/SiO2 substrate and subjected to 3 MeV Au2+ ion irradiation at room temperature to fluences ranging from 1 × 1012 to 1 × 1016 cm−2. We demonstrate that irradiation-induced defects can control optical excitations in the inner core shell of MoS2 by binding A1s- and B1s-excitons, and correlate the exciton peaks to the specific defects introduced with irradiation. The systematic increase of ion fluence produced different defect densities in MoS2, which were estimated using B/A exciton ratios and progressively increased with ion fluence. We show that up to the fluences of 1 × 1014 cm−2, the MoS2 lattice remains crystalline and defect densities can be controlled, whereas at higher fluences (≥1 × 1015 cm−2), the large number of introduced defects distorts the excitonic structure of the material. In addition to controlling excitons, defects were used to split bound and free trions, and we demonstrate that at higher fluences (1 × 1015 cm−2), both free and bound trions can be observed in the same PL spectrum. Most importantly, the lifetimes of these states exceed trion and exciton lifetimes in pristine MoS2, and PL spectra of irradiated MoS2 remains unchanged weeks after irradiation experiments. Thus, this work demonstrated the feasibility of engineering novel optical behaviors in low-dimensional materials using heavy ion irradiation. The insights gained from this study will aid in understanding the many-body interactions in low-dimensional materials and may ultimately be used to develop novel materials for optoelectronic applications.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
Methods
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
Results
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Conclusions
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Objectives: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. Methods: We assessed male high school football players (ages 14–18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. Results: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. Conclusions: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781–792)