Genetic, environmental and gender influences on attachment disorder behaviours

Background Despite current interest in attachment disorder, there is concern about its discrimination from other disorders and an unproven assumption of an environmental aetiology. Aims To test whether behaviours suggestive of attachment disorder are distinct from other childhood behavioural and emotional problems and are solely environmentally determined. Method In a community sample of 13 472 twins, we carried out factor analysis of questionnaire items encompassing behaviours indicative of attachment disorder, conduct problems, hyperactivity and emotional difficulties. We used behavioural genetic model-fitting analysis to explore the contribution of genes and environment. Results Factor analysis showed clear discrimination between behaviours suggestive of attachment disorder, conduct problems, hyperactivity and emotional problems. Behavioural genetics analysis suggested a strong genetic influence to attachment disorder behaviour, with males showing higher heritability. Conclusions Behaviours suggestive of attachment disorder can be differentiated from common childhood emotional and behavioural problems and appear to be strongly genetically influenced, particularly in boys. INTRODUCTION TOP ABSTRACT INTRODUCTION METHOD RESULTS DISCUSSION REFERENCES There have been recent attempts to codify behaviours associated with early neglect and institutionalisation (Chisolm et al, 1995; Zeanah et al, 2004) into a psychiatric category. Both DSM–IV and ICD–10 describe reactive attachment disorder, with two subtypes encompassing inhibited and disinhibited behaviour (World Health Organization, 1992; American Psychiatric Association, 1994). Questions remain about the nosology of the syndrome beyond age 5 years (American Academy of Child and Adolescent Psychiatry, 2005), therefore we simply refer to ‘attachment disorder behaviours’. We seek to extend the extant literature by testing two hypotheses: first, that the two subtypes are distinct from one another and from other common behavioural and emotional problems in young children, and second that these behavioural patterns are environmentally mediated. We capitalise on a twin study, a design that provides particular leverage in testing environmental hypotheses

Implementation of a Journal Prototype for Pregnant and Parenting Adolescents

Teenage pregnancy and childbearing remain pressing public health issues that have garnered attention from public health officials and social services agencies. This paper reports on the initial implementation and formative evaluation of a journaling program used as a means of communicating health information to pregnant and parenting adolescents (young women age 15-19) while also providing participants with a means of self-expression. The journaling prototype was implemented in a community-based agency in the Midwest by Family Support Specialists (FSSs) who made home visits on a monthly basis to assist pregnant and parenting adolescents (n = 52) with successful family planning and public health education. A mixed method approach of qualitative (analysis of journals, field notes, and responses of semi-structured interviews with FSSs) and quantitative (questionnaires from pregnant and parenting adolescent respondents) data with purposive sampling was employed to evaluate the implementation of the journaling intervention. Twenty of the 52 study participants were pregnant when the journaling intervention was implemented, while 32 were not pregnant, but recently had a child and were currently parenting. Two core themes emerged from analysis of the data after the implementation of the journals: (1) usefulness of the journal and responsiveness to participants' information needs and (2) functionality challenges. The results offer practical starting points to tailor the implementation of journaling in other contexts. Further, areas for improvement emerged regarding the distribution timeline for the journal and the content of the journal itself. As such, we discuss the lessons learned through this collaborative project and suggest opportunities for future phases of the journal intervention

Circulating RANKL is inversely related to RANKL mRNA levels in bone in osteoarthritic males

Introduction The relationship of circulating levels of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) with the expression of these molecules in bone has not been established. The objective of this study was to measure, in humans, the serum levels of RANKL and OPG, and the corresponding levels in bone of mRNA encoding these proteins. Methods Fasting blood samples were obtained on the day of surgery from patients presenting for hip replacement surgery for primary osteoarthritis (OA). Intraoperatively, samples of intertrochanteric trabecular bone were collected for analysis of OPG and RANKL mRNA, using real time RT-PCR. Samples were obtained from 40 patients (15 men with age range 50 to 79 years, and 25 women with age range 47 to 87 years). Serum total RANKL and free OPG levels were measured using ELISA. Results Serum OPG levels increased over the age range of this cohort. In the men RANKL mRNA levels were positively related to age, whereas serum RANKL levels were negatively related to age. Again, in the men serum RANKL levels were inversely related (r = -0.70, P = 0.007) to RANKL mRNA levels. Also in the male group, RANKL mRNA levels were associated with a number of indices of bone structure (bone volume fraction relative to bone tissue volume, specific surface of bone relative to bone tissue volume, and trabecular thickness), bone remodelling (eroded surface and osteoid surface), and biochemical markers of bone turnover (serum alkaline phosphatase and osteocalcin, and urinary deoxypyridinoline). Conclusion This is the first report to show a relationship between serum RANKL and the expression of RANKL mRNA in bone.David Findlay, Mellick Chehade, Helen Tsangari, Susan Neale, Shelley Hay, Blair Hopwood, Susan Pannach, Peter O'Loughlin and Nicola Fazzalar

Implementing Telerehabilitation Research For Stroke Rehabilitation With Community Dwelling Veterans: Lessons Learned

Telerehabilitation (TR) is the use of telehealth technologies to provide distance support, rehabilitation services and information exchange between people with disabilities and their clinical providers. This article discusses the barriers experienced when implementing a TR multi-site randomized controlled trial for stroke patients in their homes, and the lessons learned from conducting the study. The barriers are divided into two sections: those specific to TR and those pertinent to research overall. The TR specific barriers included the rapidly changing telecommunications and health care environment and inconsistent equipment functionality. The barriers applicable to research overall included the need for telehealth research to meet regulations in diverse departments and the rapidly expanding and changing research regulations. Solutions to the barriers included having various telehealth equipment available to allow for functionality with the currently diverse telecommunications infrastructure, rigorous pilot testing all equipment in different situations, and having biomedical engineering staff on-call and on-site

Study protocol: home-based telehealth stroke care: a randomized trial for veterans

<p>Abstract</p> <p>Background</p> <p>Stroke is one of the most disabling and costly impairments of adulthood in the United States. Stroke patients clearly benefit from intensive inpatient care, but due to the high cost, there is considerable interest in implementing interventions to reduce hospital lengths of stay. Early discharge rehabilitation programs require coordinated, well-organized home-based rehabilitation, yet lack of sufficient information about the home setting impedes successful rehabilitation. This trial examines a multifaceted telerehabilitation (TR) intervention that uses telehealth technology to simultaneously evaluate the home environment, assess the patient's mobility skills, initiate rehabilitative treatment, prescribe exercises tailored for stroke patients and provide periodic goal oriented reassessment, feedback and encouragement.</p> <p>Methods</p> <p>We describe an ongoing Phase II, 2-arm, 3-site randomized controlled trial (RCT) that determines primarily the effect of TR on physical function and secondarily the effect on disability, falls-related self-efficacy, and patient satisfaction. Fifty participants with a diagnosis of ischemic or hemorrhagic stroke will be randomly assigned to one of two groups: (a) TR; or (b) Usual Care. The TR intervention uses a combination of three videotaped visits and five telephone calls, an in-home messaging device, and additional telephonic contact as needed over a 3-month study period, to provide a progressive rehabilitative intervention with a treatment goal of safe functional mobility of the individual within an accessible home environment. Dependent variables will be measured at baseline, 3-, and 6-months and analyzed with a linear mixed-effects model across all time points.</p> <p>Discussion</p> <p>For patients recovering from stroke, the use of TR to provide home assessments and follow-up training in prescribed equipment has the potential to effectively supplement existing home health services, assist transition to home and increase efficiency. This may be particularly relevant when patients live in remote locations, as is the case for many veterans.</p> <p>Trial Registration</p> <p>Clinical Trials.gov Identifier: NCT00384748</p

Identifying resistance in wild and ornamental cherry towards bacterial canker caused by Pseudomonas syringae

Bacterial canker is a major disease of stone fruits and is a critical limiting factor to sweet cherry ( ) production worldwide. One important strategy for disease control is the development of resistant varieties. Partial varietal resistance in sweet cherry is discernible using shoot or whole tree inoculations; however, these quantitative differences in resistance are not evident in detached leaf assays. To identify novel sources of resistance to canker, we used a rapid leaf pathogenicity test to screen a range of wild cherry, ornamental species and sweet cherry × ornamental cherry hybrids with the canker pathogens, pvs , races 1 and 2, and . Several accessions exhibited limited symptom development following inoculation with each of the pathogens, and this resistance extended to 16 . strains pathogenic on sweet cherry and plum. Resistance was associated with reduced bacterial multiplication after inoculation, a phenotype similar to that of commercial sweet cherry towards nonhost strains of . . Progeny resulting from a cross of a resistant ornamental species with susceptible sweet cherry ( . ) exhibited resistance indicating it is an inherited trait. Identification of accessions with resistance to the major bacterial canker pathogens is the first step towards characterizing the underlying genetic mechanisms of resistance and introducing these traits into commercial germplasm. [Abstract copyright: © 2021 The Authors. Plant Pathology published by John Wiley & Sons Ltd on behalf of British Society for Plant Pathology.

CRIMSON [CRisis plan IMpact: Subjective and Objective coercion and eNgagement] Protocol: A randomised controlled trial of joint crisis plans to reduce compulsory treatment of people with psychosis

Background: The use of compulsory treatment under the Mental Health Act (MHA) has continued to rise in the UK and in other countries. The Joint Crisis Plan (JCP) is a statement of service users' wishes for treatment in the event of a future mental health crisis. It is developed with the clinical team and an independent facilitator. A recent pilot RCT showed a reduction in the use of the MHA amongst service users with a JCP. The JCP is the only intervention that has been shown to reduce compulsory treatment in this way. The CRIMSON trial aims to determine if JCPs, compared with treatment as usual, are effective in reducing the use of the MHA in a range of treatment settings across the UK. Methods/Design: This is a 3 centre, individual-level, single-blind, randomised controlled trial of the JCP compared with treatment as usual for people with a history of relapsing psychotic illness in Birmingham, London and Lancashire/Manchester. 540 service users will be recruited across the three sites. Eligible service users will be adults with a diagnosis of a psychotic disorder (including bipolar disorder), treated in the community under the Care Programme Approach with at least one admission to a psychiatric inpatient ward in the previous two years. Current inpatients and those subject to a community treatment order will be excluded to avoid any potential perceived pressure to participate. Research assessments will be conducted at baseline and 18 months. Following the baseline assessment, eligible service users will be randomly allocated to either develop a Joint Crisis Plan or continue with treatment as usual. Outcome will be assessed at 18 months with assessors blind to treatment allocation. The primary outcome is the proportion of service users treated or otherwise detained under an order of the Mental Health Act (MHA) during the follow-up period, compared across randomisation groups. Secondary outcomes include overall costs, service user engagement, perceived coercion and therapeutic relationships. Sub-analyses will explore the effectiveness of the JCP in reducing use of the MHA specifically for Black Caribbean and Black African service users (combined). Qualitative investigations with staff and service users will explore the acceptability of the JCPs. Discussion: JCPs offer a potential solution to the rise of compulsory treatment for individuals with psychotic disorders and, if shown to be effective in this trial, they are likely to be of interest to mental health service providers worldwide

Radiosensitization with an inhibitor of poly(ADP-ribose) glycohydrolase: A comparison with the PARP1/2/3 inhibitor olaparib

Upon DNA binding the poly(ADP-ribose) polymerase family of enzymes (PARPs) add multiple ADP-ribose subunits to themselves and other acceptor proteins. Inhibitors of PARPs have become an exciting and real prospect for monotherapy and as sensitizers to ionising radiation (IR). The action of PARPs are reversed by poly(ADP-ribose) glycohydrolase (PARG). Until recently studies of PARG have been limited by the lack of an inhibitor. Here, a first in class, specific, and cell permeable PARG inhibitor, PDD00017273, is shown to radiosensitize. Further, PDD00017273 is compared with the PARP1/2/3 inhibitor olaparib. Both olaparib and PDD00017273 altered the repair of IR-induced DNA damage, resulting in delayed resolution of RAD51 foci compared with control cells. However, only PARG inhibition induced a rapid increase in IR-induced activation of PRKDC (DNA-PK) and perturbed mitotic progression. This suggests that PARG has additional functions in the cell compared with inhibition of PARP1/2/3, likely via reversal of tankyrase activity and/or that inhibiting the removal of poly(ADP-ribose) (PAR) has a different consequence to inhibiting PAR addition. Overall, our data are consistent with previous genetic findings, reveal new insights into the function of PAR metabolism following IR and demonstrate for the first time the therapeutic potential of PARG inhibitors as radiosensitizing agents

The identification of genes important in pseudomonas syringae pv. phaseolicola plant colonisation using in vitro screening of transposon libraries

The bacterial plant pathogen Pseudomonas syringae pv. phaseolicola (Pph) colonises the surface of common bean plants before moving into the interior of plant tissue, via wounds and stomata. In the intercellular spaces the pathogen proliferates in the apoplastic fluid and forms microcolonies (biofilms) around plant cells. If the pathogen can suppress the plant’s natural resistance response, it will cause halo blight disease. The process of resistance suppression is fairly well understood, but the mechanisms used by the pathogen in colonisation are less clear. We hypothesised that we could apply in vitro genetic screens to look for changes in motility, colony formation, and adhesion, which are proxies for infection, microcolony formation and cell adhesion. We made transposon (Tn) mutant libraries of Pph strains 1448A and 1302A and found 106/1920 mutants exhibited alterations in colony morphology, motility and biofilm formation. Identification of the insertion point of the Tn identified within the genome highlighted, as expected, a number of altered motility mutants bearing mutations in genes encoding various parts of the flagellum. Genes involved in nutrient biosynthesis, membrane associated proteins, and a number of conserved hypothetical protein (CHP) genes were also identified. A mutation of one CHP gene caused a positive increase in in planta bacterial growth. This rapid and inexpensive screening method allows the discovery of genes important for in vitro traits that can be correlated to roles in the plant interactio

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration