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The receptor tyrosine kinase product of the anaplastic lymphoma kinase (ALK) gene has been implicated in oncogenesis as a product of several chromosomal translocations, although its endogeneous role in the hematopoietic and neural systems has remained poorly understood. We describe that the generation of animals homozygous for a deletion of the ALK tyrosine kinase domain leads to alterations in adult brain function. Evaluation of adult ALK homozygotes (HOs) revealed an age-dependent increase in basal hippocampal progenitor proliferation and alterations in behavioral tests consistent with a role for this receptor in the adult brain. ALK HO animals displayed an increased struggle time in the tail suspension test and the Porsolt swim test and enhanced performance in a novel object-recognition test. Neurochemical analysis demonstrates an increase in basal dopaminergic signalling selectively within the frontal cortex. Altogether, these results suggest that ALK functions in the adult brain to regulate the function of the frontal cortex and hippocampus and identifies ALK as a new target for psychiatric indications, such as schizophrenia and depression, with an underlying deregulated monoaminergic signalling.

Background The quality of nursing clinical placements has been found to vary. Placement evaluation tools for nursing students are available but lack contemporary reviews of clinical settings. Therefore, the aim of this study was to develop a feasible, valid and reliable clinical placement evaluation tool applicable to nursing student placements in Australia. Methods An exploratory mixed methods co-design project. Phase 1 included a literature review; expert rating of potential question items and Nominal Group Technique meetings with a range of stakeholders for item development. Phase 2 included on-line pilot testing of the Placement Evaluation Tool (PET) with 1263 nursing students, across all year levels at six Australian Universities and one further education college in 2019–20, to confirm validity, reliability and feasibility. Results The PET included 19-items (rated on a 5-point agreement scale) and one global satisfaction rating (a 10-point scale). Placements were generally positively rated. The total scale score (19 items) revealed a median student rating of 81 points from a maximum of 95 and a median global satisfaction rating of 9/10. Criterion validity was confirmed by item correlation: Intra-class Correlation Co-efficient ICC = .709; scale total to global score r  = .722; and items to total score ranging from .609 to .832. Strong concurrent validity was demonstrated with the Clinical Learning Environment and Supervision Scale ( r  = .834). Internal reliability was identified and confirmed in two subscale factors: Clinical Environment (Cronbach’s alpha = .94) and Learning Support (alpha = .96). Based on the short time taken to complete the survey (median 3.5 min) and students’ comments, the tool was deemed applicable and feasible. Conclusions The PET was found to be valid, reliable and feasible. Use of the tool as a quality assurance measure is likely to improve education and practice in clinical environments. Further international evaluation of the instrument is required to fully determine its psychometric properties.

Samples from eight species of corals ( Colpophyllia natans , Dendrogyra cylindrus , Diploria labyrinthiformis , Meandrina meandrites , Montastraea cavernosa , Orbicella faveolata, Pseudodiploria strigosa , and Siderastrea siderea ) that exhibited gross clinical signs of acute, subacute, or chronic tissue loss attributed to stony coral tissue loss disease (SCTLD) were collected from the Florida Reef Tract during 2016–2018 and examined histopathologically. The hallmark microscopic lesion seen in all eight species was focal to multifocal lytic necrosis (LN) originating in the gastrodermis of the basal body wall (BBW) and extending to the calicodermis, with more advanced lesions involving the surface body wall. This was accompanied by other degenerative changes in host cells such as mucocyte hypertrophy, degradation and fragmentation of gastrodermal architecture, and disintegration of the mesoglea. Zooxanthellae manifested various changes including necrosis (cytoplasmic hypereosinophilia, pyknosis); peripheral nuclear chromatin condensation; cytoplasmic vacuolation accompanied by deformation, swelling, or atrophy; swollen accumulation bodies; prominent pyrenoids; and degraded chloroplasts. Polyhedral intracytoplasmic eosinophilic periodic acid–Schiff-positive crystalline inclusion bodies (∼1–10 μm in length) were seen only in M. cavernosa and P. strigosa BBW gastrodermis in or adjacent to active lesions and some unaffected areas (without surface lesions) of diseased colonies. Coccoidlike or coccobacilloidlike structures (Gram-neutral) reminiscent of microorganisms were occasionally associated with LN lesions or seen in apparently healthy tissue of diseased colonies along with various parasites and other bacteria all considered likely secondary colonizers. Of the 82 samples showing gross lesions of SCTLD, 71 (87%) were confirmed histologically to have LN. Collectively, pathology indicates that SCTLD is the result of a disruption of host–symbiont physiology with lesions originating in the BBW leading to detachment and sloughing of tissues from the skeleton. Future investigations could focus on identifying the cause and pathogenesis of this process.

ObjectiveTo identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).SettingPatients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.ParticipantsPatients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.ResultsRelapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p<0.001). No specific factors were predictive of visual or overall disability.ConclusionsMale patients with spinal cord involvement at disease onset have a lower risk of relapsing disease and longer latency to first relapse. Steroid treatment for at least 1 month at first attack was also associated with a monophasic disease course. MOG-antibody negative seroconversion was associated with a lower risk of relapse and may help inform treatment decisions and duration.

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin. T cells are considered important for controlling skin infections. Here, the authors report that varicella-zoster virus-specific T cells preferentially persist as tissue-resident-memory T cells in rash-involved skin after recovery from zoster.

Purpose: Recovery-focused mental health treatment continues to grow, yet staff are often uncertain how best to define and implement it. As a quality assurance activity, we examined the effect of a novel orientation program embedded with a recovery framework structure, philosophy, and content, together with true lived experience codesign, on knowledge of recovery principles and acceptability. Method: Staff of a new sub-acute adolescent mental health inpatient center completed a 6-week orientation in early 2020. Recovery processes of connectedness, hope and optimism, identity, meaning, and empowerment were mapped to session topics and the structure, design, and philosophy of the program. Results: Mean knowledge scores improved from pre- to post-assessment and most (≥70%) participants reported topics as relevant, impactful, and would recommend. Approximately all (95%) comments were positive. Conclusion: Findings suggest that person-centered orientations that embed a recovery framework are promising for mental health staff orientation. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx–xx.]

This study aimed to evaluate Australian nursing students’ views of placements at seven tertiary education institutions with the use of the Placement Evaluation Tool (PET). Clinical placements are a core element of healthcare education programs around the world (Chuan and Barnett, 2012) with undergraduate nursing students required to complete a prescribed number of hours as part of their degree. The quality of nursing clinical placements varies with a range of positive and negative learning experiences. A survey design was used with a contemporary survey tool– the Placement Evaluation Tool (PET). Using Qualtrics software (Qualtrics, 2005) the on-line survey was distributed to approximately 6265 undergraduate nursing students at six Australian universities and one Technical and Further Education (TAFE) college where Bachelor of Nursing degree students were enrolled. Three Australian States were covered. Sites were selected where a project team member was employed. A total of 1263 nursing students completed the Placement Evaluation Tool (PET) − 19 items (rated 1–5), one global rating (rated 1–10) − following placement in three Australian States (July 2019−February 2020). Most - 618 (48.9%) completed a placement in acute care with placements positively rated overall. The total PET mean score was 78.3% with 29.8% being ‘extremely satisfied’ (10 out of 10 – Item 20). However, 11.0% were dissatisfied with global ratings of four or less, whilst ratings between States differed significantly (p = <0.001). One third of respondents answered a free text statement relating to placement experiences, with significantly more comments from older students (p = <0.001) and from those with ratings in the lower range (p = <0.001). Three core themes emerged: 1. Staff Attitudes to Students, 2. Environment and 3. Lifestyle. Whilst students’ clinical experiences in Australia tend to be positive a minority reported exposure to negative staff attitudes, in unsafe environments, with lifestyle detriments. Further work is required to understand and enhance student experiences. •Nursing students experience a range of positive and negative clinical experiences.•Australian students predominantly report positive experiences.•A national review of placements is essential to enhance education and safety.

Comparisons between the genomes of salmon species reveal that they underwent extensive chromosomal rearrangements following whole genome duplication that occurred in their lineage 58−63 million years ago. Extant salmonids are diploid, but occasional pairing between homeologous chromosomes exists in males. The consequences of re-diploidization can be characterized by mapping the position of duplicated loci in such species. Linkage maps are also a valuable tool for genome-wide applications such as genome-wide association studies, quantitative trait loci mapping or genome scans. Here, we investigated chromosomal evolution in Chinook salmon (Oncorhynchus tshawytscha) after genome duplication by mapping 7146 restriction-site associated DNA loci in gynogenetic haploid, gynogenetic diploid, and diploid crosses. In the process, we developed a reference database of restriction-site associated DNA loci for Chinook salmon comprising 48528 non-duplicated loci and 6409 known duplicated loci, which will facilitate locus identification and data sharing. We created a very dense linkage map anchored to all 34 chromosomes for the species, and all arms were identified through centromere mapping. The map positions of 799 duplicated loci revealed that homeologous pairs have diverged at different rates following whole genome duplication, and that degree of differentiation along arms was variable. Many of the homeologous pairs with high numbers of duplicated markers appear conserved with other salmon species, suggesting that retention of conserved homeologous pairing in some arms preceded species divergence. As chromosome arms are highly conserved across species, the major resources developed for Chinook salmon in this study are also relevant for other related species.

ImportanceChronic, intractable neuropathic pain is a common and debilitating consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no satisfactory treatment; few studies have yet to explore its aetiology.ObjectiveTo establish if myelitis-associated chronic pain in NMOSD is related to the craniocaudal location of spinal cord lesions.Method(1) Retrospective cohort of 76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpool's national NMOSD clinics, assessing current pain and craniocaudal location of cord lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab-positive Oxford patients, a subset of the retrospective cohort, assessing current craniocaudal lesion location and current pain.ResultsPatients with isolated thoracic cord myelitis at the time of pain onset were significantly more disabled and suffered more pain. Cervical and thoracic lesions that persisted from pain onset to ‘out of relapse’ follow-up (current MRI) had highly significant (p<0.01) opposing effects on pain scores (std. β=−0.46 and 0.48, respectively). Lesion length, total lesion burden and number of transverse myelitis relapses did not correlate with pain.ConclusionsPersistent, caudally located (ie, thoracic) cord lesions in AQP4-Ab-positive patients associate with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length and lesion burden. Although disability correlated with pain in isolation, it became an insignificant predictor of pain when analysed alongside craniocaudal location of lesions.

Background Increasingly, strength-based approaches to health and wellbeing interventions with Aboriginal and Torres Strait Islander Australians are being explored. This is a welcome counter to deficit-based initiatives which can represent a non-Indigenous view of outcomes of interest. However, the evidence base is not well developed. This paper presents the protocol for evaluating a strengths-based initiative which provides life coaching services to Aboriginal and Torres Strait Islander community housing tenants. The study aims to evaluate the effect of life coaching on social and emotional wellbeing (SEWB) of tenants in three Victorian regions. Methods The More Than a Landlord (MTAL) study is a prospective cohort study of Aboriginal Housing Victoria tenants aged 16 years and over that embeds the evaluation of a life coaching program. All tenant holders in one metropolitan and two regional areas of Victoria are invited to participate in a survey of SEWB, containing items consistent with key categories of SEWB as understood and defined by Aboriginal and Torres Strait Islander peoples, and key demographics, administered by Aboriginal and Torres Strait Islander peer researchers at baseline, 6 and 18 months. Survey participants are then invited to participate in strengths based life coaching, using the GROW model, for a duration of up to 18 months. Indigenous life coaches provide tenants with structured support in identifying and making progress towards their goals and aspirations, rather than needs. The study aims to recruit a minimum of 200 survey participants of which it is anticipated that approximately 73% will agree to life coaching. Discussion The MTAL study is a response to Aboriginal and Torres Strait Islander community and organisational requests to build the evidence base for an initiative originally developed and piloted within an Aboriginal controlled organisation. The study design aligns with key principles for research in Indigenous communities in promoting control, decision making and capacity building. The MTAL study will provide essential evidence to evaluate the effectiveness of strengths-based initiatives in promoting SEWB in these communities and provide new evidence about the relationship between strengths, resilience, self-determination and wellbeing outcomes. Trial registration This trial was retrospectively registered with the ISRCTN Register on the 12/7/21 with the study ID: ISRCTN33665735 .