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BACKGROUND: Research examining the connections between individual adverse childhood experiences (ACEs) and how groupings of interrelated adversities are linked with subsequent health is scarce, limiting our understanding of risk during a period of rapid expansion of ACE screening in clinical practice. The study objective was to conduct a psychometric analysis to derive latent domains of ACEs and related life events and assess the association between each domain and health outcome. METHODS: Participants (3 months-11 years) were recruited from the University of California San Francisco Benioffs Children Hospital Oakland Primary Care Clinic. Children were screened with the Pediatric ACEs and Related Life Events Screener (PEARLS) (n = 340), which assessed 17 total ACEs and related life events, including forms of abuse, household challenges, and social risks. Domains were constructed using confirmatory factor analysis and associations between the three identified domains and 14 health outcomes were assessed using multivariable linear and logistic regression models. RESULTS: Three PEARLS domains were identified: Maltreatment (ω = 0.73, ɑ=0.87), Household Challenges (ω = 0.70, ɑ=0.82), and Social Context (ω = 0.55, ɑ=0.70). Measurement invariance was supported across both gender and screening format. All domains were associated with poorer general and behavioral health and stomachaches. Maltreatment and Social Context were additionally associated with eczema while only Social Context was associated with increased odds of reporting headaches and somatic symptoms. CONCLUSION: In an underserved, urban west-coast pediatric population, the PEARLS found three adversity domains of Maltreatment, Household Challenges, and Social Context that all had an independent statistically significant association with poorer child health. The results provide a timely and more nuanced representation of risk that can inform clinical practice and policy using more targeted resources and interventions.

ObjectiveThis study aimed to examine relationships between adverse childhood experiences (ACEs) and related life events and allostatic load (AL)-"wear and tear" from chronic stress-in a pediatric population.MethodsChildren were screened with the PEdiatric ACEs and Related Life Event Screener (PEARLS) tool, a 17-item questionnaire capturing experiences of abuse, neglect, household challenges, and related life events. Biological data were available for 207 participants, and AL was operationalized using clinical or empirical cutoff points across 4 physiological systems (i.e., cardiac, metabolic, inflammatory, neurologic). Covariate-adjusted multivariable regression models were used to examine associations between AL with adversity and health.ResultsChildren (mean age = 6.5 years, range = 1-11 years) had an average AL score of 1.9 (standard deviation = 1.7), and a U-shaped relationship was observed with child's age. Continuous PEARLS and original ACE scores were not associated with AL. However, children with a reported PEARLS score of 1 to 2 or original ACEs score of 1 to 3 had 1.5 (incidence rate ratio [IRR] = 1.50, 95% confidence interval [CI] = 1.09-2.08) and 1.4 (IRR = 1.41, 95% CI = 1.08-1.84) times greater AL, respectively, compared with participants with none reported. In secondary analyses, caregiver mental illness was associated with higher child AL (adjusted IRR = 1.27, 95% CI = 1.01-1.58). AL was also associated with poorer perceived child general health (adjusted β = -0.87, 95% CI = -1.58 to -0.15) and greater odds of child obesity (adjusted odds ratio = 1.51, 95% CI = 1.23-1.89).ConclusionsMeasuring AL in a pediatric population requires careful consideration of age. Higher AL was associated with a greater number of reported adversities and worse child health.

IntroductionPrimary care-based interventions that promote nurturing caregiving relationships and early relational health may help mitigate toxic stress and promote resilience in children. This pilot study aims to: (1) describe a novel group-based, psychoeducational primary care intervention for children experiencing adverse childhood experiences (ACEs) ("The Resiliency Clinic"), (2) assess program feasibility and acceptability, and (3) explore effects on child/caregiver behavioral health.MethodsIntervention design centered on promoting supportive caregiving, caregiver/child self-regulation and co-regulation and teaching evidence-based stress management tools. Program feasibility and acceptability were assessed through attendance data and caregiver focus groups. Behavioral health measures were obtained at baseline and 8-month follow-up.ResultsOf 101 eligible families, 38 (37.6%) enrolled and attended a median of 3.00 (mean = 2.95, sd = 1.75) out of 6 sessions. Caregivers reported high satisfaction and benefits including stress management tools and connection with staff and other parents. There were modest, statistically non-significant improvements in caregiver stress (d = 0.23) and child executive functioning (d = 0.27).DiscussionIn conclusion, a group intervention teaching supportive caregiving and stress mitigation is feasible and acceptable for many families in an urban federally qualified health center (FQHC) with a signal for modest improvements in behavioral health. Future program iterations will seek to address participation barriers and expand the intervention's capacity to promote early relational health.

BackgroundWhile there is growing support for screening for Adverse Childhood Experiences (ACEs), rigorous evidence on the efficacy and preference of screening methods is needed.ObjectiveTo examine caregiver: (1) rates of disclosure of their child's exposure to ACEs using item-level response (each item can be endorsed) versus aggregate-level response (only total score reported) screening format, (2) associations between family demographic factors and disclosure by screening format, and (3) emotional reaction and experience of screening formats in a diverse, low-income pediatric population.MethodsCaregiver participants (n = 367) were randomized to complete the Pediatric ACEs and Related Life Events Screener (PEARLS) tool, in an aggregate-level response vs item-level response format from 2016-2019. Select caregivers (n = 182) participated in debriefing interviews. T-test and chi-square analyses in 2019 compared PEARLS disclosure rates and reactions between the screening modalities. Regression models explored interactions with child characteristics. Thematic analysis of interview notes captured caregiver screening experience.ResultsPEARLS disclosure rates were significantly higher in the aggregate-level response compared to the item-level response screening arm (p

BackgroundAdverse Childhood Experiences (ACEs) are associated with behavioral, mental, and clinical outcomes in children. Tools that are easy to incorporate into pediatric practice, effectively screen for adversities, and identify children at high risk for poor outcomes are lacking.ObjectiveTo examine the relationship between caregiver-reported child ACEs and related life events with health outcomes.Participants and settingParticipants (0-11 years) were recruited from the University of California San Francisco Benioff's Children Hospital Oakland Primary Care Clinic. There were 367 participants randomized.MethodsParticipants were randomized 1:1:1 to item-level (item response), aggregate-level (total number of exposures), or no screening for ACEs (control arm) with the PEdiatric ACEs and Related Life Event Screener (PEARLS). We assessed 10 ACE categories capturing abuse, neglect, and household challenges, as well as 7 additional categories. Multivariable regression models were conducted.ResultsParticipants reported a median of 2 (IQR 1-5) adversities with 76 % (n = 279) reporting at least one adversity; participants in the aggregate-level screening arm, on average, disclosed 1 additional adversity compared to item-level screening (p = 0.01). Higher PEARLS scores were associated with poorer perceived child general health (adjusted B = -0.94, 95 %CI: -1.26, -0.62) and Global Executive Functioning (adjusted B = 1.99, 95 %CI: 1.51, 2.46), and greater odds of stomachaches (aOR 1.14; 95 %CI: 1.04-1.25) and asthma (aOR 1.08; 95 %CI 1.00, 1.17). Associations did not differ by screening arm.ConclusionIn a high-risk pediatric population, ACEs and other childhood adversities remain an independent predictor of poor health. Increased efforts to screen and address early-life adversity are necessary.

Adverse Childhood Experiences (ACEs) are associated with poor health outcomes, underlining the significance of early identification and intervention. Currently, there is no validated tool to screen for ACEs exposure in childhood. To fill this gap, we designed and implemented a pediatric ACEs questionnaire in an urban pediatric Primary Care Clinic. Questionnaire items were selected and modified based on literature review of existing childhood adversity tools. Children twelve years and under were screened via caregiver report, using the developed instrument. Cognitive interviews were conducted with caregivers, health providers, and clinic staff to assess item interpretation, clarity, and English/Spanish language equivalency. Using a rapid cycle assessment, information gained from the interviews were used to iteratively change the instrument. Additional questions assessed acceptability of screening within primary care and preferences around administration. Twenty-eight (28) caregivers were administered the questionnaire. Cognitive interviews conducted among caregivers and among 16 health providers and clinic staff resulted in the changes in wording and addition of examples in the items to increase face validity. In the final instrument, no new items were added; however, two items were merged and one item was split into three separate items. While there was a high level of acceptability of the overall questionnaire, some caregivers reported discomfort with the sexual abuse, separation from caregiver, and community violence items. Preference for methods of administration were split between tablet and paper formats. The final Pediatric ACE and other Determinants of Health Questionnaire is a 17-item instrument with high face validity and acceptability for use within primary care settings. Further evaluation on the reliability and construct validity of the instrument is being conducted prior to wide implementation in pediatric practice.

ObjectiveTo characterize the accrual of long-term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data used in clinical trials have long-term prognostic value.MethodsThis is a prospective study of 517 actively managed MS patients enrolled at a single center.ResultsMore than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long-term outcomes that were no different from those of the cohort as a whole. 25-OH vitamin D serum levels were inversely associated with short-term MS disease activity; however, these levels had no association with long-term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval [CI] = 7.2-14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5-22.5%) evolved from relapsing MS to secondary progressive MS (SPMS).InterpretationRates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2-year endpoint was not a predictor of long-term stability. Finally, the data call into question the utility of annual MRI assessments as a treat-to-target approach for MS care. Ann Neurol 2016;80:499-510.

ImportanceIn multiple sclerosis (MS), upper cervical cord gray matter (GM) atrophy correlates more strongly with disability than does brain or cord white matter (WM) atrophy. The corresponding relationships in the thoracic cord are unknown owing to technical difficulties in assessing GM and WM compartments by conventional magnetic resonance imaging techniques.ObjectivesTo investigate the associations between MS disability and disease type with lower thoracic cord GM and WM areas using phase-sensitive inversion recovery magnetic resonance imaging at 3 T, as well as to compare these relationships with those obtained at upper cervical levels.Design, setting, and participantsBetween July 2013 and March 2014, a total of 142 patients with MS (aged 25-75 years; 86 women) and 20 healthy control individuals were included in this cross-sectional observational study conducted at an academic university hospital.Main outcomes and measuresTotal cord areas (TCAs), GM areas, and WM areas at the disc levels C2/C3, C3/C4, T8/9, and T9/10. Area differences between groups were assessed, with age and sex as covariates.ResultsPatients with relapsing MS (RMS) had smaller thoracic cord GM areas than did age- and sex-matched control individuals (mean differences [coefficient of variation (COV)]: 0.98 mm2 [9.2%]; P = .003 at T8/T9 and 0.93 mm2 [8.0%]; P = .01 at T9/T10); however, there were no significant differences in either the WM area or TCA. Patients with progressive MS showed smaller GM areas (mean differences [COV]: 1.02 mm2 [10.6%]; P

INTRODUCTION: Diffusion MRI tractography has been increasingly used to delineate white matter pathways in vivo for which the leading clinical application is presurgical mapping of eloquent regions. However, there is rare opportunity to quantify the accuracy or sensitivity of these approaches to delineate white matter fiber pathways in vivo due to the lack of a gold standard. Intraoperative electrical stimulation (IES) provides a gold standard for the location and existence of functional motor pathways that can be used to determine the accuracy and sensitivity of fiber tracking algorithms. In this study we used intraoperative stimulation from brain tumor patients as a gold standard to estimate the sensitivity and accuracy of diffusion tensor MRI (DTI) and q-ball models of diffusion with deterministic and probabilistic fiber tracking algorithms for delineation of motor pathways. METHODS: We used preoperative high angular resolution diffusion MRI (HARDI) data (55 directions, b = 2000 s/mm(2)) acquired in a clinically feasible time frame from 12 patients who underwent a craniotomy for resection of a cerebral glioma. The corticospinal fiber tracts were delineated with DTI and q-ball models using deterministic and probabilistic algorithms. We used cortical and white matter IES sites as a gold standard for the presence and location of functional motor pathways. Sensitivity was defined as the true positive rate of delineating fiber pathways based on cortical IES stimulation sites. For accuracy and precision of the course of the fiber tracts, we measured the distance between the subcortical stimulation sites and the tractography result. Positive predictive rate of the delineated tracts was assessed by comparison of subcortical IES motor function (upper extremity, lower extremity, face) with the connection of the tractography pathway in the motor cortex. RESULTS: We obtained 21 cortical and 8 subcortical IES sites from intraoperative mapping of motor pathways. Probabilistic q-ball had the best sensitivity (79%) as determined from cortical IES compared to deterministic q-ball (50%), probabilistic DTI (36%), and deterministic DTI (10%). The sensitivity using the q-ball algorithm (65%) was significantly higher than using DTI (23%) (p

Pelizaeus-Merzbacher disease (PMD) is a rare leukodystrophy caused by mutation of the proteolipid protein 1 gene. Defective oligodendrocytes in PMD fail to myelinate axons, causing global neurological dysfunction. Human central nervous system stem cells (HuCNS-SCs) can develop into oligodendrocytes and confer structurally normal myelin when transplanted into a hypomyelinating mouse model. A 1-year, open-label phase-1 study was undertaken to evaluate safety and to detect evidence of myelin formation after HuCNS-SC transplantation. Allogeneic HuCNS-SCs were surgically implanted into the frontal lobe white matter in four male subjects with an early-onset severe form of PMD. Immunosuppression was administered for 9 months. Serial neurological evaluations, developmental assessments, and cranial magnetic resonance imaging (MRI) and MR spectroscopy, including high-angular resolution diffusion tensor imaging (DTI), were performed at baseline and after transplantation. The neurosurgical procedure, immunosuppression regimen, and HuCNS-SC transplantation were well tolerated. Modest gains in neurological function were observed in three of the four subjects. No clinical or radiological adverse effects were directly attributed to the donor cells. Reduced T1 and T2 relaxation times were observed in the regions of transplantation 9 months after the procedure in the three subjects. Normalized DTI showed increasing fractional anisotropy and reduced radial diffusivity, consistent with myelination, in the region of transplantation compared to control white matter regions remote to the transplant sites. These phase 1 findings indicate a favorable safety profile for HuCNS-SCs in subjects with PMD. The MRI results suggest durable cell engraftment and donor-derived myelin in the transplanted host white matter.

After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify the plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential.

OBJECTIVE: We sought to determine whether vitamin D status is associated with developing new T2 lesions or contrast-enhancing lesions on brain magnetic resonance imaging (MRI) in relapsing multiple sclerosis (MS). METHODS: EPIC is a 5-year longitudinal MS cohort study at the University of California at San Francisco. Participants had clinical evaluations, brain MRI, and blood draws annually. From the overall cohort, we evaluated patients with clinically isolated syndrome or relapsing-remitting MS at baseline. In univariate and multivariate (adjusted for age, sex, ethnicity, smoking, and MS treatments) repeated measures analyses, annual 25-hydroxyvitamin D levels were evaluated for their association with subsequent new T2-weighted and gadolinium-enhancing T1-weighted lesions on brain MRI, clinical relapses, and disability (Expanded Disability Status Scale [EDSS]). RESULTS: A total of 2,362 3T brain MRI scans were acquired from 469 subjects. In multivariate analyses, each 10ng/ml higher 25-hydroxyvitamin D level was associated with a 15% lower risk of a new T2 lesion (incidence rate ratio [IRR], 0.85; 95% confidence interval [CI], 0.76-0.95; p = 0.004) and a 32% lower risk of a gadolinium-enhancing lesion (IRR, 0.68; 95% CI, 0.53-0.87; p = 0.002). Each 10ng/ml higher vitamin D level was associated with lower subsequent disability (-0.047; 95% CI, -0.091 to -0.003; p = 0.037). Higher vitamin D levels were associated with lower, but not statistically significant, relapse risk. Except for the EDSS model, all associations were stronger when the within-person change in vitamin D level was the predictor. INTERPRETATION: Vitamin D levels are inversely associated with MS activity on brain MRI. These results provide further support for a randomized trial of vitamin D supplementation.

Adverse childhood experiences (ACEs) are stressful or traumatic events that place children at risk of negative health, mental health, and behavioral outcomes. The Center for Youth Wellness (CYW), working in partnership with the Bayview Child Health Center (BCHC), pioneered ACE screening for children and adolescents. This article describes the theoretical framework and rationale for ACE screening in a primary care pediatric setting, introduces the CYW Adverse Childhood Experiences Questionnaire (CYW ACE-Q), and describes the BCHC-CYW Integrated Pediatric Care Model aimed at addressing the effects of ACEs and toxic stress. Considerations for the implementation of ACE screening are also reviewed.

This study presents a micromorphological analysis of liquefaction features (dykes, sills and sand blows) associated with the 2010 to 2011 Canterbury Earthquakes Sequence, dykes of an earlier generation of liquefaction (palaeoliquefaction) and hosting soil. The aim of this research was to determine whether diagnostic features existed that would allow robust identification of liquefaction features and discrimination of different generations of liquefaction features in thin sections. This study serves to enhance the tools available to support palaeoliquefaction studies and earthquake hazard assessment. Similarities were found in the sedimentary fabric between all forms and ages of liquefaction features distinct from hosting soil. Palaeoliquefaction features could also be distinguished on the basis of microscopic pedogenic characteristics. Liquefaction and palaeoliquefaction were investigated in two distinctive sedimentary settings: the floodplain of the Halswell River, and coastal sand dunes near or in Christchurch. Analysis was carried out on thin sections prepared from resin‐impregnated blocks of soil sediment hosting the liquefaction features. The fabric of modern liquefaction features in the alluvial and coastal system is similar, both showing a single grain micro‐structure, with moderate to well‐sorted grains with many simple packing voids and planar voids. In both environments it was possible to see evidence of fluidization such as water escape structures, cutans and silt caps. The palaeoliquefaction fabric can be distinguished from the modern liquefaction fabric by the presence of textural pedogenic features in the form of silt coating of grains, infilling of planar voids, coating and hypocoating of voids and excrement pedofeatures. The results presented in this manuscript demonstrated how thin section analysis can be a valuable tool to corroborate field identification of liquefaction features, and to discriminate between features of different relative ages where stratigraphic evidence is equivocal. [ABSTRACT FROM AUTHOR]