'On paper, you're normal': narratives of unseen health needs among women who have had children removed from their care.

BACKGROUND: Mothers who have children removed from their care often have complex needs. These women have poor health outcomes and are dying earlier than their peers from preventable and amenable causes. Yet there is little known about how health care services might mitigate these risks. This study aimed to listen to the voices of women who had children removed from their care to understand their experiences of health and healthcare. METHODS: We used a narrative approach to collect and analyse interview data with six mothers who had experienced child removal in England. Each participant was asked to reflect on their life and main health challenges. RESULTS: Three narrative subplots were developed to consolidate experiences of unmet health need: (i) 'on paper you're normal': narratives of complex need, (ii) 'in my family, everyone had issues': narratives of whole family need and (iii) 'I'm still mummy, no matter where they are': narratives of maternal identity and health. CONCLUSIONS: Findings highlight limitations within current systems of support, including a culture of distrust and women falling between the gaps of services. Women's narratives illustrate opportunities for health intervention, especially immediately following child removal.

Effectiveness and cost-effectiveness of psychiatric mother and baby units: quasi-experimental study.

BACKGROUND: Psychiatric mother and baby units (MBUs) are recommended for severe perinatal mental illness, but effectiveness compared with other forms of acute care remains unknown. AIMS: We hypothesised that women admitted to MBUs would be less likely to be readmitted to acute care in the 12 months following discharge, compared with women admitted to non-MBU acute care (generic psychiatric wards or crisis resolution teams (CRTs)). METHOD: Quasi-experimental cohort study of women accessing acute psychiatric care up to 1 year postpartum in 42 healthcare organisations across England and Wales. Primary outcome was readmission within 12 months post-discharge. Propensity scores were used to account for systematic differences between MBU and non-MBU participants. Secondary outcomes included assessment of cost-effectiveness, experience of services, unmet needs, perceived bonding, observed mother-infant interaction quality and safeguarding outcome. RESULTS: Of 279 women, 108 (39%) received MBU care, 62 (22%) generic ward care and 109 (39%) CRT care only. The MBU group (n = 105) had similar readmission rates to the non-MBU group (n = 158) (aOR = 0.95, 95% CI 0.86-1.04, P = 0.29; an absolute difference of -5%, 95% CI -14 to 4%). Service satisfaction was significantly higher among women accessing MBUs compared with non-MBUs; no significant differences were observed for any other secondary outcomes. CONCLUSIONS: We found no significant differences in rates of readmission, but MBU advantage might have been masked by residual confounders; readmission will also depend on quality of care after discharge and type of illness. Future studies should attempt to identify the effective ingredients of specialist perinatal in-patient and community care to improve outcomes.

Mothers' experiences of acute perinatal mental health services in England and Wales: a qualitative analysis.

BACKGROUND/OBJECTIVE: Perinatal mental health services are a current NHS priority and services are being increased for women. There is limited research on mothers' perspectives of these services and most research focuses on mother and baby units (MBUs). This study explored women's views of their experiences of generic wards, MBUs and crisis resolution teams. METHODS: A qualitative thematic analysis was conducted on written feedback on a service-user-designed questionnaire. One hundred and thirty-nine women recruited across 42 mental health trusts made comments. RESULTS: Two key themes were identified: support networks and staff authority. Support networks included subthemes relating to families, peers and staff. The theme of staff authority incorporated subthemes about communication, confidence in staff and service-user autonomy. All themes contributed to whether mothers felt safe in these services. Mothers reported the benefits of positive, non-coercive relationships with family and staff for their recovery. The findings highlight that the challenges women face in perinatal settings reflect the literature on general psychiatric services, particularly around coercion. CONCLUSIONS: Specific implications for mothers accessing perinatal mental health services: 1) integrated mental health care and support with babies; 2) support with separation from babies for mothers in acute wards; 3) improvement of women's relationships with social services across all services.

Harmonising outcome measurement for child focused domestic abuse interventions. Reflections on the development and implementation of a core outcome set.

There is appetite in the UK to better measure the impact of domestic violence and abuse (DVA) interventions on children. The spread of outcomes-based commissioning means outcome measurement is no longer just the territory of academic researchers but is now firmly within the purview of practitioners and policy makers. However, outcomes measured in trials only partially represent the views of those delivering and using services with respect to how success should be defined and captured. Even within trials there is huge inconsistency in the definition and measurement of important endpoints. This yields a body of evidence that is difficult to make sense of, defeating the ends for which it was produced - to improve the response to children and families who have experienced abuse. Development of Core Outcome Sets (COS) is seen as a solution to this problem, by establishing consensus across key stakeholder groups regarding a minimum standard for outcome measurement in trials, and increasingly in service delivery contexts. To date COS development has addressed outcomes relating to health conditions or interventions, with limited application to public health challenges. We reflect on our efforts to develop a COS to evaluate psychosocial interventions for children and families experiencing DVA. We highlight the value of COS development as a mechanism for improving evidence quality and the response to families experiencing abuse. Finally, we make recommendations to researchers and COS guideline developers to support this broader application of COS methodology.

Access to primary care for children and young people (CYP) in the UK: a scoping review of CYP's, caregivers' and healthcare professionals' views and experiences of facilitators and barriers.

OBJECTIVES: To examine children and young people's (CYP), caregivers' and healthcare professionals' (HCPs) views or experiences of facilitators and barriers to CYP access to UK primary care services to better understand healthcare inequity. To explore differences across CYP subpopulations with greater health needs from deprived areas, identifying as ethnic minorities, with experiences of state care, special educational needs or disabilities, chronic conditions or mental health problems. DESIGN: Scoping review. ELIGIBILITY CRITERIA: Included studies were in English, published 2012-2022 and reported: the views/experiences of CYP (0-25 years), caregivers or HCPs about accessing UK primary care; using quantitative or qualitative empirical methods. DATA SOURCES: PubMed, CINAHL, Web of Science, PsycINFO and Scopus. RESULTS: We included 47 reports (46 studies). CYP/caregivers' decision to access care was facilitated by CYP/caregivers' or their family/friends' ability to identify a health issue as warranting healthcare attention. Barriers to accessing care included perceived stigma (eg, being seen as a bad parent), embarrassment and discrimination experiences. CYP and caregivers believed longer opening hours could facilitate more timely access to care. Caregivers and HCPs reported that delayed or rejected referrals to secondary or adult care were a barrier to having needs met, especially for CYP with poor mental health. CYP and caregivers in numerous studies emphasised the importance of communication and trust with HCPs, including taking their concerns seriously, being knowledgeable and providing continuity of care for CYP. Common barriers reported across high-need subpopulations were caregivers needing knowledge and confidence to advocate for their child, gaps in HCP's knowledge and a lack of connectedness between primary and secondary care. CONCLUSIONS: Connecting general practices and community health workers/services, improving CYP/caregivers' understanding of common childhood conditions, addressing HCP's knowledge gaps in paediatric care and integrated approaches between primary and secondary care may reduce inequity in access.

Patient and caregiver characteristics associated with differential use of primary care for children and young people in the UK: a scoping review.

OBJECTIVE: To systematically map evidence to answer the research question: What is the relationship between the characteristics of children and young people (CYP) or their caregivers and primary care service use in the UK, taking into account underlying healthcare needs? DESIGN: Scoping review. SETTING: Primary care. ELIGIBILITY CRITERIA: English-language quantitative or mixed-methods studies published between 2012 and 2022. DATA SOURCES: Medline, Embase, Scopus and Web of Science Social Sciences Citation Index, and grey literature. RESULTS: 22 eligible studies were identified, covering general practice (n=14), dental health (n=4), child mental health (MN) services (n=3) and immunisation (n=1). Only eight studies (36%) controlled for variables associated with healthcare need (eg, age, birth weight and long-term conditions). In these, evidence of horizontal inequity in primary care use was reported for CYP living in deprived areas in England, with and without complex needs. Horizontal inequity was also identified in primary care MN referrals for CYP in England identifying as mixed-race, Asian or black ethnicity, compared with their white British peers. No evidence of horizontal inequity was observed, however, in primary care use for CYP in England exposed to parental depression, or for CYP children from low-income households in Scotland. Increasing CYP's age was associated with decreasing primary care use across included studies. No studies were found regarding CYP from Gypsy or Traveller communities, children in care, or those with disabilities or special educational needs. CONCLUSIONS: There is evidence that socioeconomic factors impact on CYP's primary care use, in particular age, ethnicity and deprivation. However, better quality evidence is required to evaluate horizontal inequity in use and address knowledge gaps regarding primary care use for vulnerable CYP populations and the impact of policy and practice related 'supply side' of primary care.

Perinatal healthcare for women at risk of children's social care involvement: a qualitative survey of professionals in England.

BACKGROUND: Women with complex health needs are more at risk of having children's social care involvement with their newborns than other mothers. Around the time of pregnancy, there are opportunities for health services to support women with these needs and mitigate the risk of mother-baby separation. Yet little is known about healthcare professionals' experiences of providing this support. METHODS: We administered an online survey to perinatal healthcare professionals across England (n=70 responders), including midwives, obstetricians, perinatal psychologists/psychiatrists and health visitors. We asked about their experiences of providing care for pregnant women with chronic physical conditions, mental health needs, intellectual/developmental disabilities and substance use disorders, who might be at risk of children's social care involvement. We conducted a framework analysis. RESULTS: We constructed five themes from participant data. These include (1) inaccessible healthcare for women with complex needs, (2) the challenges and importance of restoring trust, (3) services focusing on individuals, not families, (4) the necessity and caution around multidisciplinary support and (5) underfunded services inhibiting good practice. CONCLUSIONS: Women who are at risk of children's social care involvement will likely experience perinatal healthcare inequities. Our findings suggest that current perinatal healthcare provision for this population is inadequate and national guidelines need updated to inform support.

"People don't have the answers": A qualitative exploration of the experiences of young people with Long COVID.

Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted (n = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study (n = 11) or its patient and public involvement and engagement (PPIE) group (n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID.

Why was the study done? Capturing the broad impact of Long COVID and the experiences of young people and their families living with persisting symptoms will help to identify the unique needs and challenges experienced by this population and help shape effective treatments going forward. What did the researchers do? Researchers conducted interviews with children and young people living with Long COVID. Parents of young people were also invited to participate to gain a comprehensive understanding of the effects of Long COVID and its impact on the wider family. What did the researchers find? Analysis of 11 interviews with young people and 5 with parents revealed four themes central to young people's experiences of living with Long COVID relating to unknowns and uncertainties, identity shifts, the impact of symptoms and accessing support. What do findings mean? Findings from the study suggest the implications of Long COVID were far-reaching and impairing. Current treatment options were not perceived as widely available or effective, suggesting a need for further research to develop effective interventions for young people living with Long COVID.

Child maltreatment and parental domestic violence and abuse, co-occurrence and the effect on lifetime outcomes in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Exposure to child maltreatment (CM), and parental domestic violence and abuse (DVA), impose considerable adverse life outcomes in both the short and long term, yet, the extent and effects of their co-occurrence on outcomes have not been comprehensively quantified. This study describes the analysis of data from the Avon Longitudinal Study of Parents and Children, quantifying the prevalence of CM, parental DVA, co-occurrence rates, and the impact of different combinations of childhood exposures on life outcomes (health, economic, and likelihood of perpetrating intimate partner violence as a young person). Childhood exposure prevalences were estimated at 41.7% for any form of CM, 19.3% for parental DVA, and 49.0% for exposure to at least one form of CM and/or parental DVA. Co-occurring parental DVA was reported in 21%-42% of CM-exposed households. Sexual abuse was reported in 2% of parental DVA-exposed households, whilst co-occurrence of other forms of CM ranged between 19% and 41%. Co-occurring CM and parental DVA exposures were associated with increased risks of drug use, anxiety, depression, smoking, unemployment, social welfare use, and perpetration of intimate partner violence as a young person - highlighting the intergenerational effects of exposure. Increased risks across a wider range of adverse outcomes were associated with child-reported awareness of parental DVA, compared to parent-reported DVA exposure. The high cumulative prevalence of childhood exposure to CM and/or parental DVA, and the scale of the resulting adverse impacts emphasise the need for policies and family interventions sensitive to the possibility of co-occurring forms of abuse.

Parental health in the context of public family care proceedings: A scoping review of evidence and interventions.

BACKGROUND: Child protective services (CPS), or their equivalent, have statutory power to remove children from birth parents in instances of child abuse, neglect, or concerns around parenting capacity via public family care proceedings. Parents who have children subject to proceedings, 'birth parents', often have complex health and social care needs. OBJECTIVE: We aimed to review what is known about the health needs of birth parents and the interventions implemented to support these health needs. METHODS: We searched PubMed, Scopus, and grey literature using a systematic strategy of key concepts "health", "care proceedings", and "parents". We included all publications in English that reported parental health in the context of care proceedings from the 1st of January 2000 to the 1st of March 2021. RESULTS: Included studies (n = 61) reported on maternal health (57 %) or the health of both parents (40 %), with only one study reporting on fathers alone. We conceptually categorised parental health need (n = 41) into i) mental health, ii) physical health, iii) substance misuse, iv) developmental disorders, and v) reproductive health. Health inequities and poor access to services were described across all categories, with longstanding issues often pre-dating proceedings or the child's birth. All interventions supporting parental health (n = 20) were targeted at mothers, with some supporting fathers (n = 8), formally or informally. We grouped similar interventions into three types: alternative family courts, wrap-around services, and specialist advocacy/peer support. CONCLUSIONS: Parents who have children subject to care proceedings have complex health needs that pre-date CPS concerns. The studies included in our review strongly suggest that health issues are exacerbated by child removal, triggering deteriorations in mental health, poor antenatal health for subsequent pregnancies, and avoidable mortality. Findings highlight the need for targeted and timely intervention for parents to improve whole-family outcomes. There are models that have been designed, implemented, and tested using relationship-based, trauma-informed, multidisciplinary, family-focused, and long-term approaches.

Family adversity and health characteristics associated with intimate partner violence in children and parents presenting to health care: a population-based birth cohort study in England.

BACKGROUND: Little is known about the clinical characteristics of children and parents affected by intimate partner violence (IPV) presenting in health-care settings. We examined the associations between family adversities, health characteristics, and IPV in children and parents using linked electronic health records (EHRs) from primary and secondary care between 1 year before and 2 years after birth (the first 1000 days). We compared parental health problems in in children and parents with and without recorded IPV. METHODS: We developed a population-based birth cohort of children and parents (aged 14-60 years) in England, comprising linked EHRs from mother-child pairs (with no identified father) and mother-father-child triads. We followed the cohort across general practices (Clinical Practice Research Datalink GOLD), emergency departments, outpatient visits, hospital admissions, and mortality records. Family adversities included 33 clinical indicators of parental mental health problems, parental substance misuse, adverse family environments, and high-risk child maltreatment-related presentations. Parental health problems included 12 common comorbidities, ranging from diabetes and cardiovascular diseases to chronic pain or digestive diseases. We used adjusted and weighted logistic-regression models to estimate the probability of IPV (per 100 children and parents) associated with each adversity, and period prevalences of parental health problems associated with IPV. FINDINGS: We included 129 948 children and parents, comprising 95 290 (73·3%) mother-father-child triads and 34 658 (26·7%) mother-child pairs only between April 1, 2007, and Jan 29, 2020. An estimated 2689 (2·1%) of 129 948 children and parents (95% CI 2·0-2·3) had recorded IPV and 54 758 (41·2%; 41·5-42·2) had any family adversity between 1 year before and 2 years after birth. All family adversities were significantly associated with IPV. Most parents and children with IPV had recorded adversities (1612 [60·0%] of 2689) before their first IPV recording. The probability of IPV was 0·6 per 100 children and parents (95% CI 0·5-0·6) with no adversity, increasing to 4·4 per 100 children per parents (4·2-4·7) with one adversity, and up to 15·1 per 100 parents and children (13·6-16·5) with three of more adversities. Mothers with IPV had a significantly higher prevalence of both physical (73·4% vs 63·1%, odds ratio [OR] 1·6, 95% CI 1·4-1·8) and mental health problems (58·4% vs 22·2%, OR 4·9, 4·4-5·5) than mothers without IPV. Fathers with IPV had a higher prevalence of mental health problems (17·8% vs 7·1%, OR 2·8, 2·4-3·2) and similar prevalences of physical health problems than those without IPV (29·6% vs 32·4%, OR 0·9, 0·8-1·0). INTERPRETATION: Two in five of the children and parents presenting to health care had recorded parental mental health problems, parental substance misuse, adverse family environments, or high-risk presentations of maltreatment in the first 1000 days. One in 22 children and parents with family adversity also had recorded IPV before age 2 years. Primary and secondary care staff should safely ask about IPV when parents or children present with family adversity or health problems associated with IPV, and respond appropriately. FUNDING: NIHR Policy Research Programme.

The Modern Slavery Core Outcome Set: A Survivor-Driven Consensus on Priority Outcomes for Recovery, Wellbeing, and Reintegration.

There is no consensus on the outcomes needed for the recovery and reintegration of survivors of modern slavery and human trafficking. We developed the Modern Slavery Core Outcome Set (MSCOS) to address this gap. We conducted three English-language reviews on the intervention outcomes sought or experienced by adult survivors: a qualitative systematic review (4 databases, 18 eligible papers, thematic analysis), a rapid review of quantitative intervention studies (four databases, eight eligible papers, content analysis) and a gray literature review (2 databases, 21 websites, a call for evidence, 13 eligible papers, content analysis). We further extracted outcomes from 36 pre-existing interview transcripts with survivors, and seven interviews with survivors from underrepresented groups. We narrowed down outcomes via a consensus process involving: a three-stage E-Delphi survey (191 respondents); and a final consensus workshop (46 participants). We generated 398 outcomes from our 3 reviews, and 843 outcomes from interviews. By removing conceptual and literal duplicates, we reduced this to a longlist of 72 outcomes spanning 10 different domains. The E-Delphi produced a 14-outcome shortlist for the consensus workshop, where 7 final outcomes were chosen. Final outcomes were: "long-term consistent support," "secure and suitable housing," "safety from any trafficker or other abuser," "access to medical treatment," "finding purpose in life and self-actualisation," "access to education," and "compassionate, trauma-informed services." The MSCOS provides outcomes that are accepted by a wide range of stakeholders and that should be measured in intervention evaluation.

Child and family-focused interventions for child maltreatment and domestic abuse: development of core outcome sets.

BACKGROUND: The current evidence for child maltreatment (CM) and domestic violence and abuse (DVA) interventions is limited by the diversity of outcomes evaluated and the variety of measures used. The result is studies that are difficult to compare and lack focus on outcomes reflecting service user or provider priorities. OBJECTIVE: To develop core outcome sets (COSs) for evaluations of child and family-focused interventions for: (1) CM and (2) DVA. DESIGN: We conducted a two-stage consensus process. Stage 1: a long list of candidate outcomes across CM and DVA was developed through rapid systematic reviews of intervention studies, qualitative and grey literature; stakeholder workshops; survivor interviews. Stage 2: three-panel, three-round e-Delphi surveys for CM and DVA with consensus meetings to agree with the final COSs. PARTICIPANTS: 287 stakeholders participated in at least one stage of the process (ie, either CM or DVA COS development): workshops (n=76), two e-Delphi surveys (n=170) and consensus meetings (n=43). Stakeholders included CM and DVA survivors, practitioners, commissioners, policymakers and researchers. RESULTS: Stage 1 identified 335 outcomes categorised into 9 areas and 39 domains. Following stage 2, the final five outcomes included in the CM-COS were: child emotional health and well-being; child's trusted relationships; feelings of safety; child abuse and neglect; service harms. The final five outcomes in the DVA-COS were: child emotional health and well-being; caregiver emotional health and well-being; family relationships; freedom to go about daily life; feelings of safety. CONCLUSIONS: We developed two COSs for CM and DVA with two common outcomes (child emotional health and well-being; feelings of safety). The COSs reflect shared priorities among service users, providers and researchers. Use of these COSs across trials and service evaluations for children and families affected by CM and DVA will make outcome selection more consistent and help harmonise research and practice.

Protocol for developing core outcome sets for evaluation of psychosocial interventions for children and families with experience or at risk of child maltreatment or domestic abuse.

INTRODUCTION: Recognition that child maltreatment (CM) and domestic violence and abuse (DVA) are common and have serious and long-term adverse health consequences has resulted in policies and programmes to ensure that services respond to and safeguard children and their families. However, high-quality evidence about how services can effectively intervene is scant. The value of the current evidence base is limited partly because of the variety of outcomes and measures used in evaluative studies. One way of addressing this limitation is to develop a core outcome set (COS) which is measured and reported as a minimum standard in the context of trials and other types of evaluative research. The study described in this protocol aims to develop two discrete COSs for use in future evaluation of psychosocial interventions aimed at improving outcomes for children and families at risk or with experience of (1) CM or (2) DVA. METHODS AND ANALYSIS: A two-phase mixed methods design: (1) rapid reviews of evidence, stakeholder workshops and semistructured interviews with adult survivors of CM/DVA and parents of children who have experienced CM/DVA and (2) a three panel adapted E-Delphi Study and consensus meeting. This study protocol adheres to reporting guidance for COS protocols and has been registered on the Core Outcome Measures for Effectiveness Trials (COMET) database. ETHICS AND DISSEMINATION: We will disseminate our findings through peer-reviewed and open access publications, the COMET website and presentations at international conferences. We will engage with research networks, journal editors and funding agencies to promote awareness of the CM-COS and DVA-COS. We will work with advisory and survivor and public involvement groups to coproduce a range of survivor, policy and practice facing outputs.Approval for this study has been granted by the Research Ethics Committee at University College London.

Validated shipping noise maps of the Northeast Atlantic.

Underwater noise pollution from shipping is globally pervasive and has a range of adverse impacts on species which depend on sound, including marine mammals, sea turtles, fish, and many invertebrates. International bodies including United Nations agencies, the Arctic Council, and the European Union are beginning to address the issue at the policy level, but better evidence is needed to map levels of underwater noise pollution and the potential benefits of management measures such as ship-quieting regulations. Crucially, corroboration of noise maps with field measurements is presently lacking, which undermines confidence in their application to policymaking. We construct a computational model of underwater noise levels in the Northeast Atlantic using Automatic Identification System (AIS) ship-tracking data, wind speed data, and other environmental parameters, and validate this model against field measurements at 4 sites in the North Sea. Overall, model predictions of the median sound level were within ±3 dB for 93% of the field measurements for one-third octave frequency bands in the range 125 Hz-5 kHz. Areas with median noise levels exceeding 120 dB re 1 µPa and 20 dB above modelled natural background sound were predicted to occur in the Dover Strait, the Norwegian trench, near to several major ports, and around offshore infrastructure sites in the North Sea. To our knowledge, this is the first study to quantitatively validate large-scale modelled noise maps with field measurements at multiple sites. Further validation will increase confidence in deeper waters and during winter months. Our results highlight areas where anthropogenic pressure from shipping noise is greatest and will inform the management of shipping noise in the Northeast Atlantic. The good agreement between measurements and model gives confidence that models of shipping noise can be used to inform future policy and management decisions to address shipping noise pollution.

Proteomic identification of novel substrates of a protein isoaspartyl methyltransferase repair enzyme.

We report the use of a proteomic strategy to identify hitherto unknown substrates for mammalian protein l-isoaspartate O-methyltransferase. This methyltransferase initiates the repair of isoaspartyl residues in aged or stress-damaged proteins in vivo. Tissues from mice lacking the methyltransferase (Pcmt1(-/-)) accumulate more isoaspartyl residues than their wild-type littermates, with the most "damaged" residues arising in the brain. To identify the proteins containing these residues, brain homogenates from Pcmt1(-/-) mice were methylated by exogenous repair enzyme and the radiolabeled methyl donor S-adenosyl-[methyl-(3)H]methionine. Methylated proteins in the homogenates were resolved by both one-dimensional and two-dimensional electrophoresis, and methyltransferase substrates were identified by their increased radiolabeling when isolated from Pcmt1(-/-) animals compared with Pcmt1(+/+) littermates. Mass spectrometric analyses of these isolated brain proteins reveal for the first time that microtubule-associated protein-2, calreticulin, clathrin light chains a and b, ubiquitin carboxyl-terminal hydrolase L1, phosphatidylethanolamine-binding protein, stathmin, beta-synuclein, and alpha-synuclein, are all substrates for the l-isoaspartate methyltransferase in vivo. Our methodology for methyltransferase substrate identification was further supplemented by demonstrating that one of these methyltransferase targets, microtubule-associated protein-2, could be radiolabeled within Pcmt1(-/-) brain extracts using radioactive methyl donor and exogenous methyltransferase enzyme and then specifically immunoprecipitated with microtubule-associated protein-2 antibodies to recover co-localized protein with radioactivity. We comment on the functional significance of accumulation of relatively high levels of isoaspartate within these methyltransferase targets in the context of the histological and phenotypical changes associated with the methyltransferase knock-out mice.