Models of care in secure services for people with intellectual and developmental disability: Implementing the Walkway to Wellness.

BACKGROUND: Changes to policy around inpatient services for people with intellectual and developmental disability (IDD) who offend, have led to a need for services to reconsider their models of care. This has led to calls for more tailored, patient-centred care models, with less reliance solely on offence-related treatment programmes which can be unsuitable for a growing proportion of patients with more complex cognitive and behavioural difficulties. In response, the Walkway to Wellness (W2W) was developed at one National Health Service Trust providing secure services to people with IDD, with the intention of delivering a more collaborative, co-produced and goal-oriented care model that was better understood by staff and patient stakeholders. AIMS: To evaluate the implementation of the W2W using Normalisation Process Theory (NPT), an evidence-based theoretical approach is used across a number of health settings. METHODS: Staff were invited to complete a short questionnaire, using the NPT informed Normalisation Measure Development questionnaire, at two time points along the implementation process. Patients were invited to complete a simplified questionnaire. Both groups were asked for their views on the W2W and the process of its implementation. RESULTS: Although the W2W was more familiar to staff at the second time point, scores on the four NPT constructs showed a trend for it being less embedded in practice, with significant results concerning the ongoing appraisal of the new model. Patient views were mixed; some saw the benefit of more goal-oriented processes, but others considered it an additional chore hindering their own perceived goals. CONCLUSION: Early involvement of all stakeholders is required to enhance the understanding of changes to models of care. Live feedback should be used to refine and revise the model to meet the needs of patients, carers and staff members.

Interventions to Reduce Parental Substance Use, Domestic Violence and Mental Health Problems, and Their Impacts Upon Children's Well-Being: A Systematic Review of Reviews and Evidence Mapping.

INTRODUCTION: Children exposed to parental intimate partner violence and abuse, mental illness, and substance use experience a range of problems which may persist into adulthood. These risks often co-occur and interact with structural factors such as poverty. Despite increasing evidence, it remains unclear how best to improve outcomes for children and families experiencing these adversities and address the complex issues they face. AIMS AND METHODS: Systematic review of systematic reviews. We searched international literature databases for systematic reviews, from inception to 2021, to provide an evidence overview of the range and effectiveness of interventions to support children and families where these parental risk factors had been identified. RESULTS: Sixty-two systematic reviews were included. The majority (n = 59) focused on interventions designed to address single risk factors. Reviews mostly focused on parental mental health (n = 38) and included psychological interventions or parenting-training for mothers. Only two reviews assessed interventions to address all three risk factors in combination and assessed structural interventions. Evidence indicates that families affected by parental mental health problems may be best served by integrated interventions combining therapeutic interventions for parents with parent skills training. Upstream interventions such as income supplementation and welfare reform were demonstrated to reduce the impacts of family adversity. CONCLUSION: Most intervention approaches focus on mitigating individual psychological harms and seek to address risk factors in isolation, which presents potentially significant gaps in intervention evidence. These interventions may not address the cumulative impacts of co-occurring risks, or social factors that may compound adversities.

Improving access to primary care and annual health checks for people who have a learning disability: a multistakeholder qualitative study.

OBJECTIVES: To investigate key stakeholders' views on how to improve access to primary care in general practice settings for people with learning disabilities (or intellectual disabilities). Further to explore how inequalities and barriers in specific areas including annual health checks might be addressed. DESIGN: A qualitative study design was used with data collected during focus groups, interviews and open-response surveys; data analysis was thematic and informed by stakeholder consultation. Processes to facilitate quality included triangulation of stakeholder perspectives, triangulation of data collection methods and checking interpretation of findings with participants. SETTING: UK regional services including learning disability organisations, primary care general practitioner (GP) clinical practice networks and supported housing organisations. PARTICIPANTS: Sixteen people participated in the study: four people with learning disabilities participated in a focus group; four relatives completed an interview or survey; eight GPs, practice nurses and supported housing managers participated in interviews. RESULTS: Five overarching themes describing approaches to improve primary care access for people with learning disabilities were identified including: prioritisation, proactivity, innovation and improvement, personalisation and prevention and follow-up. Definitions of themes were described and illustrated with quotes. Ten recommendations informed by the thematic analysis, stakeholder consultation, research and primary care guidance were codeveloped with people with learning disabilities. CONCLUSIONS: All stakeholders identified problems, with primary care interfaces being misaligned with the needs of people with learning disabilities. The recommendations informed by all stakeholders can be used to guide development of service provision to better meet the needs of people with learning disabilities in primary care. Future research should explore professionals' understanding of reasonable adjustments.

Outcome measures in psoriatic arthritis: Where next?

OBJECTIVE: To provide an overview of commonly used outcome measure in psoriatic arthritis (PsA). BACKGROUND: PsA is a heterogenous inflammatory arthritis, associated with psoriasis that affects between 0.1% and 2% of the population and approximately one in three patients with psoriasis. Psoriatic arthritis places a significant burden on patients' overall quality of life and is associated with a range of comorbidities. Although assessment of patients and monitoring of symptoms has greatly improved over the last 2 decades, capturing disease activity in this multisystem disease remains challenging. Previous efforts have traditionally focussed on assessment of individual disease domains, however recent evidence suggests that composite measurements, particularly those incorporating patient reported outcomes may not only help monitor disease activity more accurately, but also help in accurately validating therapy outcomes in PsA patients. PURPOSE: This review discusses currently used outcome measurements in PsA and also highlights the importance of emerging measurements such as biomarkers and their possible role in capturing treatment response.

Parental intimate partner violence and abuse during the COVID-19 pandemic: Learning from remote and hybrid working to influence future support.

OBJECTIVES: The COVID-19 pandemic has exacerbated intimate partner violence and abuse. Incidents of intimate partner violence and abuse have increased as a result of household tensions due to enforced coexistence (multiple national lockdowns and working from home practices), economic stress related to loss of income, the disruption of social and protective networks and the decreased access to support services. This study aimed to understand how female survivors of parental intimate partner violence and abuse have experienced the adapted multi-agency response to intimate partner violence and abuse during the pandemic and consider learning from remote and hybrid working to influence future support. METHOD: This study adopted a qualitative research design, utilizing semi-structured interviews and a focus group. Data collection took place between March and September 2021. In total, 17 female survivors of intimate partner violence and abuse took part in the project; we conducted the semi-structured interviews via telephone (n = 9) and conducted an online focus group (n = 8). RESULTS: Findings identified that services for those experiencing intimate partner violence and abuse need to be innovative, flexible and adaptable and 'reach out' to survivors rather than waiting for survivors to 'reach in' and ask for support. Findings show that the digital space highlights 'missed opportunities' for engagement with both professionals and peers and the potential for digital poverty is a key implication, which risks entrenching existing inequalities. CONCLUSION: In-depth consideration needs to be given to the design, delivery and evaluation of online interventions and provision of support to improve access and acceptability of services, maximize their effectiveness and to support the safety of survivors.

Advances for future working following an online dramatherapy group for adults with intellectual disabilities and mental ill health during the COVID-19 pandemic: A service evaluation for Cumbria, Northumberland Tyne and Wear NHS Foundation Trust.

Background: During the COVID-19 pandemic, social distancing measures were enforced and the national lockdown underlined our reliance on virtual means as a way to communicate. This new way of interacting highlighted that people with an intellectual disability were a large proportion of a digitally excluded population. Methods: A service evaluation, using a mixed method design in the form of four self-reported outcome measures and qualitative feedback. Findings: Clinical services need to continue when face to face sessions are not possible. Remote groups can be an alternative option not only when self-isolating due to pandemics but when living in remote locations, having physical health problems or excessive expenses and travel costs. Conclusions: Online dramatherapy groups can be a beneficial alternative when face to face groups are not possible or challenging to attend due to access difficulties. Online groups can offer opportunities to meet with peers, build relationships, improve confidence and learn new skills in technology.

Psoriatic arthritis: prospects for the future.

Psoriatic arthritis (PsA) is a form of chronic inflammatory arthritis associated with psoriasis and a multitude of other symptoms, most commonly arthritis, dactylitis, enthesitis and axial involvement. PsA is significantly heterogeneous, with a highly variable clinical course of PsA. Patients may experience significant or mild skin and joint symptoms, with some patients developing rapidly progressing joint destruction and skin symptoms. Despite the range of symptom severity, PsA is frequently associated with significantly impaired quality of life from joint destruction, as well as chronic pain and a range of comorbidities such as depression and cardiovascular disease. Currently, there are no definitive diagnostic tests for PsA, with diagnosis remaining challenging owing to the heterogeneous presentation and course of the disease. Presently, the CASPAR criteria are often used to aid rheumatologists in distinguishing PsA from other inflammatory arthritides. Treatment options for patients have been expanded over the last two decades with the emerging clinical utility of biological therapies. However, early identification and diagnosis of patients and effective disease control remain unmet medical needs within the PsA community. In addition, predicting response to treatment also remains a challenge to rheumatologists. This review highlights the current hurdles faced by healthcare professionals in the diagnosis and management of PsA patients and provides future action points for consideration by the members of the multidisciplinary team who treat PsA patients.

A systematic review of community psychosocial group interventions for adults with intellectual disabilities and mental health conditions.

BACKGROUND: People with intellectual disabilities have a high risk of developing mental ill-health. Treatment is often neglected and diagnosis is misattributed to a person's disability. Standard psychosocial interventions can improve a person's well-being. This review aimed to understand what interventions are being delivered, any benefits, and future recommendations. METHODS: Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed, and the review registered with PROSPERO-CRD42020160254. Databases searched included: MEDLINE, Embase, and PsycINFO. A framework synthesis approach was used to present the findings. RESULTS: There are limited psychosocial interventions offered for this population. When groups are delivered having a creative element, multiple activities over a short period of time, with breaks and group rules outcomes can be improved. CONCLUSIONS: Adaptations and reasonable adjustments should be used specifically to a person's ability. A mixed-method design allows people to share their experiences alongside quantitative data that provides clinical information.

Measuring Physical Function in Psoriatic Arthritis: Comparing the Multidimensional Health Assessment Questionnaire to the Health Assessment Questionnaire-Disability Index.

OBJECTIVE: To compare physical function scales of the Multidimensional Health Assessment Questionnaire (MDHAQ) with that of the Health Assessment Questionnaire-Disability Index (HAQ-DI) in patients with psoriatic arthritis (PsA), and to examine whether either questionnaire is less prone to "floor effects." METHODS: Data were collected prospectively from 2018 to 2019 across 3 UK hospitals. All patients completed physical function scales within the MDHAQ and HAQ-DI in a single clinic visit. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. RESULTS: Two hundred ten patients completed the clinic visit; 1 withdrew consent. Thus, 209 were analyzed. Sixty percent were male, with mean age of 51.7 years and median disease duration of 7 years. In clinic, median MDHAQ and HAQ-DI including/excluding aids scores were 0.30, 0.50, and 0.50 respectively. Although the median score for HAQ-DI was higher than for MDHAQ, the difference between the 2 scores was mostly within 1.96 SDs from the mean, suggesting good agreement. The ICCs demonstrated excellent test-retest reliability for both the MDHAQ and HAQ-DI. Similar numbers of patients scored 0 on the MDHAQ and HAQ-DI including/excluding aids (48, 47, and 49, respectively). Using a score of ≤ 0.5 as a cutoff for minor functional impairment, 23 patients had a MDHAQ ≤ 0.5 when their HAQ-DI including aids was > 0.5. Conversely, 4 patients had a MDHAQ > 0.5 when the HAQ-DI including aids was ≤ 0.5. CONCLUSION: Both the MDHAQ and HAQ-DI appear to be similar in detecting floor effects in patients with PsA.

Art Therapy in the Digital World: An Integrative Review of Current Practice and Future Directions.

BACKGROUND: Psychotherapy interventions increasingly utilize digital technologies to improve access to therapy and its acceptability. Opportunities that digital technology potentially creates for art therapy reach beyond increased access to include new possibilities of adaptation and extension of therapy tool box. Given growing interest in practice and research in this area, it is important to investigate how art therapists engage with digital technology or how (and whether) practice might be safely adapted to include new potential modes of delivery and new arts media. METHODS: An integrative review of peer-reviewed literature on the use of digital technology in art therapy was conducted. The methodology used is particularly well suited for early stage exploratory inquiries, allowing for close examination of papers from a variety of methodological paradigms. Only studies that presented empirical outcomes were included in the formal analysis. FINDINGS: Over 400 records were screened and 12 studies were included in the synthesis, pertaining to both the use of digital technology for remote delivery and as a medium for art making. Included studies, adopting predominantly qualitative and mixed methods, are grouped according to their focus on: art therapists' views and experiences, online/distance art therapy, and the use of digital arts media. Recurring themes are discussed, including potential benefits and risks of incorporating digital technology in sessions with clients, concerns relating to ethics, resistance toward digital arts media, technological limitations and implications for therapeutic relationship and therapy process. Propositions for best practice and technological innovations that could make some of the challenges redundant are also reviewed. Future directions in research are indicated and cautious openness is recommended in both research and practice. CONCLUSION: The review documents growing research illustrating increased use of digital technology by art therapists for both online delivery and digital art making. Potentially immense opportunities that technology brings for art therapy should be considered alongside limitations and challenges of clinical, pragmatic and ethical nature. The review aims to invite conversations and further research to explore ways in which technology could increase relevance and reach of art therapy without compromising clients' safety and key principles of the profession.

Comparing the Visual Analog Scale and the Numerical Rating Scale in Patient-reported Outcomes in Psoriatic Arthritis.

OBJECTIVE: Patient self-report scales are invaluable in psoriatic arthritis (PsA), as they allow physicians to rapidly assess patient perspectives of disease activity. We aimed to assess the agreement of the visual analog scale (VAS), a 100-mm horizontal line, and the numerical rating scale (NRS), a 21-point scale ranging from 0 to 10 in increments of 0.5, in patients with PsA. METHODS: Data were collected prospectively across 3 UK hospital trusts from 2018 to 2019. All patients completed the VAS and NRS for pain, arthritis, skin psoriasis (PsO), and global disease activity. A subset completed an identical pack 1 week later. Demographic and clinical data were also collected. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. Spearman rank correlation coefficients were used to assess dependency between scale scores and clinical variables. RESULTS: Two hundred ten patients completed the study; 1 withdrew consent. Thus, 209 were analyzed. For pain, arthritis, skin PsO, and global disease activity, the difference between the VAS and NRS lay mostly within 1.96 SD of the mean, suggesting reasonable agreement between the 2 scales. Among the patients, 64.1% preferred the NRS. The ICCs demonstrated excellent test-retest reliability for both VAS and NRS. Higher VAS and NRS scores were associated with increased tender/swollen joint count, poorer functional status, and greater life impact. CONCLUSION: The VAS and NRS show reasonable agreement in key patient-reported outcomes in PsA. Results from both scales are correlated with disease severity and life impact.

A randomised controlled feasibility study of interpersonal art psychotherapy for the treatment of aggression in people with intellectual disabilities in secure care.

BACKGROUND: Rates of aggression in inpatient secure care are higher than in other psychiatric inpatient settings. People with intellectual disabilities in secure care require adapted psychological treatments. Interpersonal art psychotherapy incorporates the use of creative art making approaches by participants, thus reducing sole reliance upon verbal interactions during psychotherapy for people who may have communication difficulties. During interpersonal art psychotherapy, participants are individually supported by their therapist to consider how they conduct relationships. This includes the influence and impact of interpersonal issues resulting in repeated patterns of conflict. The key feasibility objectives were to assess recruitment and retention rates, follow-up rates and trial procedures such as randomisation, allocation and identifying any practical or ethical problems. In addition, a preliminary 'signal' for the intervention was considered and an indicative sample size calculation completed. The acceptability of a potential third trial arm attentional control condition, mindful colouring-in, was assessed using four single-case design studies and a UK trial capacity survey was conducted. METHODS: Adult patients with intellectual disabilities in secure care were recruited and randomised to either interpersonal art psychotherapy or delayed treatment in this multi-site study. Outcomes were assessed using weekly observations via the Modified Overt Aggression Scale and a range of self-report measures. Within study reporting processes, qualitative interviews and a survey were completed to inform trial feasibility. RESULTS: Recruitment procedures were successful. The target of recruiting 20 participants to the trial from multiple sites was achieved within 8 months of the study opening. All participants recruited to the treatment arm completed interpersonal art psychotherapy. Between-group differences of interpersonal art psychotherapy versus the delayed treatment control showed a 'signal' effect-size of .65 for total scores and .93 in the verbal aggression sub-scale. There were no amendments to the published protocol. The assessment of key feasibility objectives were met and the trial procedures were acceptable to all involved in the research. CONCLUSION: This study suggested that a randomised controlled trial of interpersonal art psychotherapy is acceptable and feasible. TRIAL REGISTRATION: ISRCTN14326119 (Retrospectively Registered).

Using Arts-Based Therapies to Improve Mental Health for Children and Young People With Physical Health Long-Term Conditions: A Systematic Review of Effectiveness.

Background: Children with physical health long-term conditions (LTCs) have increased risk of mental health difficulties relative to healthy peers. However, availability of psychological support integrated into pediatric physical health settings is limited, and there are long waiting times for access to child mental health services. Arts-based therapies involve using creative media to develop a therapeutic relationship, and offer a potential alternative to talking-based therapies. The aim of this systematic review is to establish the effectiveness of arts-based therapies for improving the mental health of children with physical health LTCs. Methods: The review protocol was published on PROSPERO. Four electronic databases were searched (Medline, Embase, Cinahl, and PsycINFO), plus hand searches of two key journals and relevant reviews, and forward/back citations searches of selected articles were conducted. The Effective Public Health Practice Project (EPHPP) Quality Assessment Tool was used to assess bias in selected articles. Second reviewers completed 10% of article screening and 20% of bias assessments. The findings were synthesized narratively. Results: Sixteen studies met inclusion criteria and demonstrated some improvements on indicators of mental health and well-being including quality of life, coping behaviors, anxiety, self-concept, and mood. However, replication across interventions and outcomes was absent. Overall, the quality of evidence of effectiveness in the studies reviewed was moderate/weak. This was due to bias in study design; other limitations included a lack of detail on intervention components, e.g., use of a manual, and single recruitment sites. Conclusions: The heterogeneity of existing research evaluating arts-based therapies for children with physical health LTCs limits conclusions about effectiveness. Suggestions are made to inform the design of future research studies to help build a robust evidence base.

Young People Who Display Harmful Sexual Behaviors and Their Families: A Qualitative Systematic Review of Their Experiences of Professional Interventions.

It is estimated that 30-50% of all childhood sexual abuse involves other young people as perpetrators. The treatment of harmful sexual behavior (HSB) in young people has evolved from interventions developed for use with adult perpetrators of sexual offenses. Increasingly, these approaches were not seen as appropriate for use with young people. The purpose of this qualitative systematic review was to establish what intervention components are viewed as acceptable or useful by young people and their families in order to inform the development of interventions for young people with HSB. We conducted searches across 14 electronic databases as well as contacting experts to identify relevant studies. Thirteen qualitative studies were included in the analysis, reporting findings from intervention studies from the United Kingdom, United States, New Zealand, Australia, and Ireland. Thematic analysis was used to combine findings from the studies of young people and parent/carers views. Five key themes were identified as critical components of successful interventions for young people with HSB. These included the key role of the relationship between the young person and practitioner, the significance of the role of parents and carers, the importance of considering the wider context in which the abuse has occurred, the role of disclosure in interventions, and the need to equip young people with skills as well as knowledge. The evidence was limited by the small number of studies that were mainly from the perspectives of adolescent males.

Psychodynamic art psychotherapy for the treatment of aggression in an individual with antisocial personality disorder in a secure forensic hospital: A single-case design study.

The aim of this single-case study was to investigate the responses to psychodynamic art psychotherapy from a man who had a diagnosis of antisocial personality disorder and ongoing aggressive behavior in a secure care setting. The intervention was 19 sessions of psychodynamic art psychotherapy lasting up to 1 hr per week. This study uses a single-case design with pretreatment, treatment, and posttreatment follow-up assessment of symptoms using multiple methods reported by the therapist, other staff members, and the patient. Treatment progress was assessed by (a) repeated self-report symptom measurements, (b) continuous assessment of observed aggressive behavior and risk incident reports in the hospital, (c) pre-post treatment assessment of relationship patterns and interpersonal schemas, and (d) interviews with the patient and his nurse at 9-month follow-up, retrospectively assessing the change. The patient showed a clinically significant reduction pre-post and pre-follow-up in symptoms. Behavioral observations indicated a reduction of overt aggression and risk-related incidents. Comparison of the Core Conflictual Relationship Theme pre-post treatment indicated positive changes in interpersonal schemas. This illustrative systematic single-case study highlights the potential for investigation of a novel psychotherapeutic approach that has in turn led to further developments in clinical research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Experiences of Young People with Harmful Sexual Behaviors in Services: A Qualitative Study.

Young people are responsible for a significant number of the sexual offenses that are committed every year. These young people are generally referred to specialist services for treatment. This article explores the health characteristics and service experiences of 117 young people with sexual behavior problems, and the issues that services face when working with them. The study is based on analysis of 117 case files, identified from nine specialist services in the UK. The case files were thematically analyzed. Case files provided information on the following topics: the reasons why the young people were referred to harmful sexual behavior services; the young people's personal characteristics; their medical and mental health problems; the young people's interests and aspirations; their attitudes toward services and interventions; continued problematic sexual incidents in services; progress in services; and post-service experiences. Overall, the findings of the study indicate that these young people have a number of strengths, but often have problems across a range of personal and health domains. A number of them continue to remain sexually and generally violent in services, particularly in residential settings, which has risk management implications for staff.

Interpersonal art psychotherapy for the treatment of aggression in people with learning disabilities in secure care: a protocol for a randomised controlled feasibility study.

BACKGROUND: Art psychotherapy has greater potential for use with adults with mild to moderate learning disabilities as it places less of a burden on verbal interaction to achieve positive therapeutic, psychological, and behavioural goals. The feasibility study objectives include testing procedures, outcomes, validated tools, recruitment and attrition rates, acceptability, and treatment fidelity for manualised interpersonal art psychotherapy. METHODS: Adult males and females with mild to moderate learning disabilities will be recruited from four NHS secure hospitals. Twenty patients will be recruited and randomly assigned to one of two treatment groups: fifteen 1-h individual sessions of manualised interpersonal art psychotherapy, or a treatment as usual waiting list control group. The Modified Overt Aggression Scale will be administered to both treatment arms. Four patients will be recruited to a single-case design component of the study exploring the acceptability of an attentional condition. DISCUSSION: This multi-site study will assist in future trial planning and inform feasibility including, procedures, treatment acceptability, therapist adherence, and estimation of samples size for a definitive RCT.

Mind-mindedness in parents of looked-after children.

The studies reported here aimed to test the proposal that mind-mindedness is a quality of personal relationships by assessing mind-mindedness in caregiver-child dyads in which the relationship has not spanned the child's life or in which the relationship has been judged dysfunctional. Studies 1 and 2 investigated differences in mind-mindedness between adoptive parents (ns = 89, 36) and biological parents from the general population (ns = 54, 114). Both studies found lower mind-mindedness in adoptive compared with biological parents. The results of Study 2 showed that this group difference was independent of parental mental health and could not fully be explained in terms of children's behavioral difficulties. Study 3 investigated differences in mind-mindedness in foster carers (n = 122), parents whose children had been the subject of a child protection plan (n = 172), and a community sample of biological parents (n = 128). The level of mind-mindedness in foster carers and parents who were involved with child protection services was identical and lower than that in the community sample; children's behavioral difficulties could not account for the difference between the 2 groups of biological parents. In all 3 studies, nonbiological carers' tendency to describe their children with reference to preadoption or placement experiences was negatively related to mind-mindedness. These findings are in line with mind-mindedness being a relational construct. (PsycINFO Database Record

Dendritic cells and pluripotency: unlikely allies in the pursuit of immunotherapy.

As the fulcrum on which the balance between the opposing forces of tolerance and immunity has been shown to pivot, dendritic cells (DC) hold significant promise for immune intervention in a variety of disease states. Here we discuss how the directed differentiation of human pluripotent stem cells may address many of the current obstacles to the use of monocyte-derived DC in immunotherapy, providing a novel source of previously inaccessible DC subsets and opportunities for their scale-up, quality control and genetic modification. Indeed, given that it is the immunological legacy DC leave behind that is of therapeutic value, rather than their persistence per se, we propose that immunotherapy should serve as an early target for the clinical application of pluripotent stem cells.