An online acceptance, commitment, and self-compassion based treatment to decrease psychological distress in people with type 2 diabetes: A feasibility randomised-controlled trial

BACKGROUND AND PURPOSE: This study explored the feasibility and acceptability of conducting a larger trial of a self-guided, online self-compassion and acceptance and commitment therapy (ACT) focused treatment among people with type 2 diabetes (T2D) to decrease psychological distress. MATERIALS AND METHODS: This study was a two-arm, parallel, feasibility randomised controlled trial with nested qualitative methods. UK adults with T2D were randomly (1:1) allocated to a five-week online self-compassion and ACT treatment or waitlist control. Information regarding recruitment, trial retention, and treatment completion was collected, and post-treatment semi-structured interviews were conducted to assess feasibility and acceptability. Self-report measures of psychological distress (depression, anxiety, diabetes distress) and potential treatment processes (self-compassion and psychological flexibility) were completed as secondary feasibility outcomes. RESULTS: Fifty-five (60.44 %) out of 91 people who accessed the study link were eligible to participate. Of these, 33 eligible participants (60 %) were randomly assigned to treatment (n = 19) or control arms (waitlist; n = 14). While treatment completion was 47.37 %, trial retention rates were 39.39 % (5-week follow-up) and 21.2 % (9-week follow-up). Secondary feasibility outcomes of treatment effect estimates are difficult to interpret in light of low treatment completion and trial retention rates. CONCLUSION: A larger trial of the self-guided, online self-compassion treatment to decrease psychological distress in people with T2D may be beneficial, but it has limited feasibility in its current form. Further efforts are needed to improve treatment acceptability of online self-compassion and ACT focused treatment and trial procedures

Meningococcal disease in children in Merseyside, England:a 31 year descriptive study

Meningococcal disease (MCD) is the leading infectious cause of death in early childhood in the United Kingdom, making it a public health priority. MCD most commonly presents as meningococcal meningitis (MM), septicaemia (MS), or as a combination of the two syndromes (MM/MS). We describe the changing epidemiology and clinical presentation of MCD, and explore associations with socioeconomic status and other risk factors. A hospital-based study of children admitted to a tertiary children's centre, Alder Hey Children's Foundation Trust, with MCD, was undertaken between 1977 to 2007 (n = 1157). Demographics, clinical presentations, microbiological confirmation and measures of deprivation were described. The majority of cases occurred in the 1-4 year age group and there was a dramatic fall in serogroup C cases observed with the introduction of the meningococcal C conjugate (MCC) vaccine. The proportion of MS cases increased over the study period, from 11% in the first quarter to 35% in the final quarter. Presentation with MS (compared to MM) and serogroup C disease (compared to serogroup B) were demonstrated to be independent risk factors for mortality, with odds ratios of 3.5 (95% CI 1.18 to 10.08) and 2.18 (95% CI 1.26 to 3.80) respectively. Cases admitted to Alder Hey were from a relatively more deprived population (mean Townsend score 1.25, 95% CI 1.09 to 1.41) than the Merseyside reference population. Our findings represent one of the largest single-centre studies of MCD. The presentation of MS is confirmed to be a risk factor of mortality from MCD. Our study supports the association between social deprivation and MCD

Positive practices : solution-focused and narrative therapeutic techniques with children with sexually harmful behaviours

This article explores the use of solution-focused and Narrative Therapeutic approaches with a boy who had sexually harmful behaviours. The paper will highlight the practical challenges of working with someone who is 'problem-saturated' through institutionalisation and who is also subjected to powerful discourses claiming the 'truth' about him. The use of solution-focused and Narrative Therapeutic principles and approaches will be demonstrated in the work described, in a way that allows the reader to reflect on how these may differ from modernist understandings and responses to this behaviour

Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon

BACKGROUND: Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB) transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. RESULTS: Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA) system that is capable of activating the expression of genes under control of a Tet response element (TRE) promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. CONCLUSION: Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene-trap tTA could provide a means for both annotating mouse genes and creating a resource of mice that express a regulable transcription factor in temporally- and tissue-specific patterns for conditional gene expression studies. These mice would be a valuable resource to the mouse genetics community for purpose of dissecting mammalian gene function

STAT2 deficiency and susceptibility to viral illness in humans

Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections

Does a local financial incentive scheme reduce inequalities in the delivery of clinical care in a socially deprived community? A longitudinal data analysis.

BACKGROUND: Socioeconomic deprivation is associated with inequalities in health care and outcomes. Despite concerns that the Quality and Outcomes Framework pay-for-performance scheme in the UK would exacerbate inequalities in primary care delivery, gaps closed over time. Local schemes were promoted as a means of improving clinical engagement by addressing local health priorities. We evaluated equity in achievement of target indicators and practice income for one local scheme. METHODS: We undertook a longitudinal survey over four years of routinely recorded clinical data for all 83 primary care practices. Sixteen indicators were developed that covered five local clinical and public health priorities: weight management; alcohol consumption; learning disabilities; osteoporosis; and chlamydia screening. Clinical indicators were logit transformed from a percentage achievement scale and modelled allowing for clustering of repeated measures within practices. This enabled our study of target achievements over time with respect to deprivation. Practice income was also explored. RESULTS: Higher practice deprivation was associated with poorer performance for five indicators: alcohol use registration (OR 0.97; 95 % confidence interval 0.96,0.99); recorded chlamydia test result (OR 0.97; 0.94,0.99); osteoporosis registration (OR 0.98; 0.97,0.99); registration of repeat prednisolone prescription (OR 0.98; 0.96,0.99); and prednisolone registration with record of dual energy X-ray absorptiometry (DEXA) scan/referral (OR 0.92; 0.86,0.97); practices in deprived areas performed better for one indicator (registration of osteoporotic fragility fracture (OR 1.26; 1.04,1.51). The deprivation-achievement gap widened for one indicator (registered females aged 65-74 with a fracture referred for a DEXA scan; OR 0.97; 0.95,0.99). Two other indicators indicated a similar trend over two years before being withdrawn (registration of fragility fracture and over-75 s with a fragility fracture assessed and treated for osteoporosis risk). For one indicator the deprivation-achievement gap reduced over time (repeat prednisolone prescription (OR 1.01; 1.01,1.01). Larger practices and those serving more affluent areas earned more income per patient than smaller practices and those serving more deprived areas (t = -3.99; p =0.0001). CONCLUSIONS: Any gaps in achievement between practices were modest but mostly sustained or widened over the duration of the scheme. Given that financial rewards may not reflect the amount of work undertaken by practices serving more deprived patients, future pay-for-performance schemes also need to address fairness of rewards in relation to workload

EMPOWERED trial: protocol for a randomised control trial of digitally supported, highly personalised and measurement-based care to improve functional outcomes in young people with mood disorders

Objectives Many adolescents and young adults with emerging mood disorders do not achieve substantial improvements in education, employment, or social function after receiving standard youth mental health care. We have developed a new model of care referred to as 'highly personalised and measurement-based care' (HP&MBC). HP&MBC involves repeated assessment of multidimensional domains of morbidity to enable continuous and personalised clinical decision-making. Although measurement-based care is common in medical disease management, it is not a standard practice in mental health. This clinical effectiveness trial tests whether HP&MBC, supported by continuous digital feedback, delivers better functional improvements than standard care and digital support. Method and analysis This controlled implementation trial is a PROBE study (Prospective, Randomised, Open, Blinded End-point) that comprises a multisite 24-month, assessor-blinded, follow-up study of 1500 individuals aged 15-25 years who present for mental health treatment. Eligible participants will be individually randomised (1:1) to 12 months of HP&MBC or standardised clinical care. The primary outcome measure is social and occupational functioning 12 months after trial entry, assessed by the Social and Occupational Functioning Assessment Scale. Clinical and social outcomes for all participants will be monitored for a further 12 months after cessation of active care. Ethics and dissemination This clinical trial has been reviewed and approved by the Human Research Ethics Committee of the Sydney Local Health District (HREC Approval Number: X22-0042 & 2022/ETH00725, Protocol ID: BMC-YMH-003-2018, protocol version: V.3, 03/08/2022). Research findings will be disseminated through peer-reviewed journals, presentations at scientific conferences, and to user and advocacy groups. Participant data will be deidentified. Trial registration number ACTRN12622000882729

Pitch Processing Sites in the Human Auditory Brain

Lateral Heschl's gyrus (HG), a subdivision of the human auditory cortex, is commonly believed to represent a general “pitch center,” responding selectively to the pitch of sounds, irrespective of their spectral characteristics. However, most neuroimaging investigations have used only one specialized pitch-evoking stimulus: iterated-ripple noise (IRN). The present study used a novel experimental design in which a range of different pitch-evoking stimuli were presented to the same listeners. Pitch sites were identified by searching for voxels that responded well to the range of pitch-evoking stimuli. The first result suggested that parts of the planum temporale are more relevant for pitch processing than lateral HG. In some listeners, pitch responses occurred elsewhere, such as the temporo-parieto-occipital junction or prefrontal cortex. The second result demonstrated a different pattern of response to the IRN and raises the possibility that features of IRN unrelated to pitch might contribute to the earlier results. In conclusion, it seems premature to assign special status to lateral HG solely on the basis of neuroactivation patterns. Further work should consider the functional roles of these multiple pitch processing sites within the proposed network

Earth BioGenome Project: Sequencing life for the future of life.

Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort