Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes.

Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.

Interpersonal process features of collaboration between probation and behavioral health practitioners.

This study sought to identify and conceptualize the central interpersonal process features that comprise good collaboration between behavioral health practitioners (BHPs) and probation officers (POs). Eighteen POs and 21 BHPs from geographically adjacent jurisdictions in a Midwestern state each participated in one of six focus groups. Researchers systematically coded focus group transcripts for interpersonal collaborative themes using both inductive and deductive strategies. Seven core themes-shared values and beliefs, communication and information sharing, knowledge of the other, trust, respect, team-based decision making, and equitable contribution-were identified and coded for importance, as indexed by frequency, latent tone, and group consensus. An initial working operational definition of these constructs, based on practitioners' dialogue, is also provided. This study is one of the first to provide BHPs and POs who work with justice-involved people with prescriptive guidance about interpersonal actions and approaches that will best serve their professional collaborative efforts. Future research should examine whether these constructs hold across other samples and contexts and work to fully operationalize and measure these constructs and their importance for affecting various outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

BACKGROUND: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. OBJECTIVE: To report COVID-19 rates in pwMS according to vaccine serology. METHODS: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. RESULTS: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34-4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57-1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. CONCLUSION: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

Persistent Paternalism: The Instantiation of Gendered Attributions in the System Response to Girls.

Prior research suggests that the juvenile legal system does too little to address the sources and underlying reasons for girls' court referrals. Drawing on attribution theories, the current study examined perspectives that characterize the response of the system to girls' behaviors. Data from this study were derived from a multimethod, qualitative study on system-involved girls. We find that court actors hold gendered attributions of girls' delinquency, in turn informing their decision-making about how to treat and sanction girls. Paternalism remains a persistent feature in how the system locates, defines, and responds to girls through varying gendered attributions. The findings lend further support to attribution perspectives that suggest implicit gender-biases influence court actor decision-making, exacerbating the challenges girls face in and out of the juvenile legal system. By extension, this study offers concrete policy and practice implications for systems change and improving its response to girls.

Vascular disease risk factors in multiple sclerosis: Effect on metabolism and brain volumes.

BACKGROUND: Vascular disease risk factors (VDRF) such as hypertension, hyperlipidemia, obesity, diabetes and heart disease likely play a role in disease progression in people with multiple sclerosis (PwMS) (Marrie, Rudick et al. 2010). Studies exploring the mechanistic connection between vascular disease and MS disease progression are scant. We hypothesized that phosphate energy metabolism impairment in PwMS with VDRFs (VDRF+) will be greater compared to PwMS without VDRFs (VDRF-) and is related to increased brain atrophy in VDRF+. To test this hypothesis, we planned to study the differences in the high energy phosphate (HEP) metabolites in cerebral gray matter as assessed by 31P magnetic resonance spectroscopic imaging (MRSI) and MRI brain volumetric in the VDRF+ and VDRF- PwMS at four different timepoints over a 3 yearlong period using a 7T MR system. We present here the results from the cross-sectional evaluation of HEP metabolites and brain volumes. We also evaluated the differences in clinical impairment, blood metabolic biomarkers and quality of life in VDRF+ and VDRF- PwMS in this cohort. METHODS: Group differences in high energy phosphate metabolites were assessed from a volume of interest in the occipital region using linear mixed models. Brain parenchymal and white matter lesion volumes were determined from MR anatomic images. We present here the cross-sectional analysis of the baseline data collected as part of a longitudinal 3 yearlong study where we obtained baseline and subsequent 6-monthly clinical and laboratory data and annual 7T MRI volumetric and 31P MR spectroscopic imaging (MRSI) data on 52 PwMS with and without VDRF. Key clinical and laboratory outcomes included: body mass index (BMI), waist and thigh circumferences and disability [Expanded Disability Status Scale (EDSS)], safety (complete blood count with differential, complete metabolic), lipid panel including total cholesterol and HbA1C. We analyzed clinical and laboratory data for the group differences using student's t or χ2 test. We investigated relationship between phosphate metabolites and VDRF using mixed effect linear regression. RESULTS: Complete MRI data were available for 29 VDRF+, age 56.3 (6.8) years [mean (SD)] (83% female), and 23 VDRF-, age 52.5 (7.5) years (57% female) individuals with MS. The mean value of normalized adenosine triphosphate (ATP) (calculated as the ratio of ATP to total phosphate signal in a voxel) was decreased by 4.5% (p < .05) in VDRF+ compared to VDRF- MS group. White matter lesion (WML) volume fraction in VDRF+ individuals {0.007 (0.007)} was more than doubled compared to VDRF- participants {0.003 (0.006), p= .02}. CONCLUSIONS: We found significantly lower brain ATP and higher inorganic phosphate (Pi) in those PwMS with VDRFs compared to those without. ATP depletion may reflect mitochondrial dysfunction. Ongoing longitudinal data analysis from this study, not presented here, will evaluate the relationship of phosphate metabolites, brain atrophy and disease progression in PwMS with and without vascular disease.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Response to COVID-19 booster vaccinations in seronegative people with multiple sclerosis.

BACKGROUND: People with MS treated with anti-CD20 therapies and fingolimod often have attenuated responses to initial COVID-19 vaccination. However, uncertainties remain about the benefit of a 3rd (booster) COVID-19 vaccine in this group. METHODS: PwMS without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. RESULTS: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There was no association between laboratory evidence of prior COVID-19 and seroconversion following vaccine 3. CONCLUSIONS: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

COVID-19 Vaccine Response in People with Multiple Sclerosis.

OBJECTIVE: The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines in people with multiple sclerosis (MS). METHODS: Four hundred seventy-three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID-19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV-2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS-CoV-2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response. RESULTS: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01-0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01-0.12) were associated with lower seroconversion following the SARS-CoV-2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Preliminary data on cellular T-cell immunity showed 40% of seronegative subjects had measurable anti-SARS-CoV-2 T cell responses. INTERPRETATION: Some disease modifying therapies convey risk of attenuated serological response to SARS-CoV-2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 20219999:n/a-n/a.

DCE-MRI of Brain Fluid Barriers: In Vivo Water Cycling at the Human Choroid Plexus.

Metabolic deficits at brain-fluid barriers are an increasingly recognized feature of cognitive decline in older adults. At the blood-cerebrospinal fluid barrier, water is transported across the choroid plexus (CP) epithelium against large osmotic gradients via processes tightly coupled to activity of the sodium/potassium pump. Here, we quantify CP homeostatic water exchange using dynamic contrast-enhanced MRI and investigate the association of the water efflux rate constant (kco) with cognitive dysfunction in older individuals. Temporal changes in the longitudinal relaxation rate constant (R1) after contrast agent bolus injection were measured in a CP region of interest in 11 participants with mild cognitive dysfunction [CI; 73 ± 6 years] and 28 healthy controls [CN; 72 ± 7 years]. kco was determined from a modified two-site pharmacokinetic exchange analysis of the R1 time-course. Ktrans, a measure of contrast agent extravasation to the interstitial space was also determined. Cognitive function was assessed by neuropsychological test performance. kco averages 5.8 ± 2.7 s-1 in CN individuals and is reduced by 2.4 s-1 [ca. 40%] in CI subjects. Significant associations of kco with global cognition and multiple cognitive domains are observed. Ktrans averages 0.13 ± 0.07 min-1 and declines with age [-0.006 ± 0.002 min-1 yr-1], but shows no difference between CI and CN individuals or association with cognitive performance. Our findings suggest that the CP water efflux rate constant is associated with cognitive dysfunction and shows an age-related decline in later life, consistent with the metabolic disturbances that characterize brain aging.

Microbial Control Agents for Fungus Gnats (Diptera: Sciaridae: Lycoriella) Affecting the Production of Oyster Mushrooms, Pleurotus spp.

Infestations of fungus gnats (Diptera: Sciaridae) can reduce the production of oyster mushrooms (Pleurotus spp.) grown as food crops within controlled environments. The objectives of this study were to assess the efficacy of Bacillus thuringiensis var. israelensis (Bti) and Steinernema feltiae against fungus gnat larvae. A bioassay was developed, whereby pasteurized straw was inoculated with Pleurotus columbinus and treated with Bti (Gnatrol®), S. feltiae (Nemashield®), or water. Fungus gnats (Lycoriella sp.) were released into each bioassay container for ovipositing onto the straw, thereby exposing the F1 larvae to treated or untreated substrate. Sticky cards within the containers entrapped fungus gnats emerging from the substrate as an indicator of larval survivorship. Following three bioassays, fewer fungus gnats emerged from straw treated with Bti compared to S. feltiae and the water control. Three additional bioassays using Pleurotus ostreatus also demonstrated that fewer fungus gnats emerged from straw treated with Bti compared to S. feltiae and the untreated control. Steinernema feltiae was generally ineffective. Monitoring substrate weight in the bioassay containers over time indicated that Bti and S. feltiae did not impede colonization by P. ostreatus. Incorporating Bti into straw substrate is a promising approach for managing fungus gnats infesting Pleurotus spp.

Gray matter blood-brain barrier water exchange dynamics are reduced in progressive multiple sclerosis.

BACKGROUND AND PURPOSE: To compare transcapillary wall water exchange, a putative marker of cerebral metabolic health, in brain T2 white matter (WM) lesions and normal appearing white and gray matter (NAWM and NAGM, respectively) in individuals with progressive multiple sclerosis (PMS) and healthy controls (HC). METHODS: Dynamic-contrast-enhanced 7T MRI data were obtained from 19 HC and 23 PMS participants. High-resolution pharmacokinetic parametric maps representing tissue microvascular and microstructural properties were created by shutter-speed (SS) paradigm modeling to obtain estimates of blood volume fraction (vb ), water molecule capillary efflux rate constant (kpo ), and the water capillary wall permeability surface area product (Pw S ≡ vb *kpo ). Linear regression models were used to investigate differences in (i) kpo and Pw S between groups in NAWM and NAGM, and (ii) between WM lesions and NAWM in PMS. RESULTS: High-resolution parametric maps were produced to visualize tissue classes and resolve individual WM lesions. Normal-appearing gray matter kpo and Pw S were significantly decreased in PMS compared to HC (p ≤ .01). Twenty-one T2 WM lesions were analyzed in 10 participants with PMS. kpo was significantly decreased in WM lesions compared to PMS NAWM (p < .0001). CONCLUSIONS: Transcapillary water exchange is reduced in PMS NAGM compared to HC and is further reduced in PMS WM lesions, suggesting pathologically impaired brain metabolism. kpo provides a sensitive measure of cerebral metabolic activity and/or coupling, and can be mapped at higher spatial resolution than conventional imaging techniques assessing metabolic activity.

Human Trafficking Cases Presenting within Child Advocacy Centers.

Although human trafficking of minors is an increasing concern within the United States, very little information is known about how trafficking cases are processed within child advocacy centers (CACs). The current study addresses this gap in the literature by providing descriptive information about victims, service referrals, and prosecutorial outcomes for human trafficking cases presenting at CACs across a Midwestern state. The data originates from a state-wide study focused on understanding the scope of human trafficking cases. Specifically, the dataset includes 210 youth presenting at CACs over a three-year period of time. In this sample, the typical human trafficking case involved sex trafficking of a self-identified white female victim, with an offender known to the victim. Most child survivors passing through CACs were referred to medical and mental health services, although these service referrals did not greatly differ across at-risk versus substantiated trafficking cases. Overall, the findings suggest that CACs are uniquely positioned to encounter human trafficking cases and provide needed services to trafficking survivors. Finally, recommendations are provided for CACs regarding the intake and identification of trafficking cases more broadly.

Family-based Intervention for Legal System-involved Girls: A Mixed Methods Evaluation.

The increased proportion of juvenile court-involved girls has spurred interest to implement and evaluate services to reduce girls' system involvement. The purpose of this study was to examine the effectiveness of a family-based intervention by using a dominant sequential mixed methods evaluation approach. First, we examined quantitative data using a quasi-experimental design to determine whether the family-based intervention reduced recidivism among court-involved girls. Propensity score matching (PSM) was used to construct statistically equivalent groups to compare one-year recidivism outcomes for girls who received the court-run family-based intervention (n = 181) to a group of girls on probation who did not receive the intervention (n = 803). Qualitative interviews (n = 39) were conducted to contextualize the quantitative findings and highlighted the circumstances that family-focused interventions for court-involved girls. Girls who received the program had slightly lower recidivism rates following the intervention. The qualitative findings contextualized the quasi-experimental results by providing an explanation as to the girls' family circumstances and insights into the mechanisms of the intervention. Results highlighted the importance of family-focused interventions for juvenile justice-involved girls. These findings have practical and policy implications for the use interventions-beyond the individual level-with adjudicated girls and offer suggestions for ways to improve their effectiveness using a community psychology lens. In addition, this paper includes a discussion of evaluating of juvenile court programming from a community psychology perspective including strengths, challenges, and considerations for future work in this area.

Aberrant white matter microstructure in treatment-resistant schizophrenia✰.

Treatment response in schizophrenia divides into three subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS), and ultra-treatment-resistant schizophrenia (UTRS). White matter abnormalities could drive antipsychotic resistance but little work has investigated differences between TRS and UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were obtained using tract-based spatial statistics. Analysis of variance and post-hoc t-tests were conducted for each measure. Those with TRS had lower FA than healthy controls in superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). No post-hoc tests survived corrections for multiple comparisons and no differences in MD, AD or RD were observed. These data suggest that microstructural deficits in white matter could contribute to TRS but suggest that other mechanisms may be more relevant for UTRS.

Serum neurofilament-light concentration and real-world outcome in MS.

BACKGROUND: Prognostication in multiple sclerosis (MS) remains challenging. Biomarkers capable of providing this information at diagnosis would be valuable in shaping therapeutic decisions. Measurement of neurofilament light (NfL) has shown promise in predicting clinical outcomes in established MS, but its ability to predict outcomes in real-world cohorts at diagnosis requires further validation. METHODS: We used linear regression to evaluate the relationship between serum NfL (sNfL), measured at the time of diagnosis with short-term (1-year) and medium-term (5-year) clinical outcomes in 164 people with MS from a real-world, population-based cohort. Cox proportional hazards regression was used to analyse the association between sNfL and subsequent hazard of relapse or sustained accumulation of disability (SAD). Analyses were adjusted for age and disease-modifying treatment (DMT). RESULTS: sNfL concentration at diagnosis was modestly associated with baseline EDSS score (ß = 0.272, 95% CI 0.051 to 0.494, p = 0.016). However, no significant associations were found between baseline sNfL and odds of relapse at 12-months, 5-year EDSS change, or the hazard of relapse or SAD over 5 years follow-up. Dichotomising baseline sNfL according to the median sNfL did not change these findings. CONCLUSIONS: sNfL appears to be of limited clinical utility in predicting future irreversible neurological disability in a largely untreated real-world population, and remains insufficiently validated to shape treatment decisions at the time of diagnosis. Further studies may be needed for sNfL to be considered as a prognostic marker in the MS clinic. However the masking effect of DMTs on the natural disease trajectory will continue to pose challenges.

Victim or Prostitute? The Classification of Commercial Sex Events Involving Minors in the National Incident-Based Reporting System.

Sex trafficking is recognized as a national problem that inflicts serious harm on its victims, yet, legislative responses to trafficking vary depending on jurisdiction. Federal legislation considers youths who engage in commercial sex acts as trafficking victims. States, however, vary in the evidence required to prove a juvenile is a victim of sex trafficking, as opposed to an offender of prostitution. Using four years of data from the National Incident-Based Reporting System, we compared details of commercial sex incidents involving youths who were identified as trafficking victims or arrested as prostitutes. Beyond legislative differences, comparisons between cases are discussed to illuminate how state law enforcement officials legally classify these events involving adolescents (i.e., as victims or prostitutes). Further, we consider the policy implications of the findings.

Observation of Reduced Homeostatic Metabolic Activity and/or Coupling in White Matter Aging.

BACKGROUND AND PURPOSE: Transvascular water exchange plays a key role in the functional integrity of the blood-brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange. METHODS: A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (vb ) and capillary water efflux rate constant (kpo ) were determined by fitting changes in the 1 H2 O longitudinal relaxation rate constant (R1 ) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images. RESULTS: R1 values and WM volume showed similar trajectories of age-related decline. Among all subjects, vb and kpo averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s-1 , respectively. While vb showed minimal changes over the 40-year-age span of participants, kpo declined 0.06 s-1 (ca. 3%) per year (r = -.66; P < .0005), from near 4 s-1 at age 30 to ca. 2 s-1 at age 70. The association remained significant after controlling for WM volume. CONCLUSIONS: Previous studies have shown that kpo tracks Na+ , K+ -ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in kpo observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.

A Meta-Analysis of Program Characteristics for Youth with Disruptive Behavior Problems: The Moderating Role of Program Format and Youth Gender.

There is high variability in efficacy for interventions for youth with disruptive behavior problems (DBP). Despite evidence of the unique correlates and critical consequences of girls' DBP, there is a dearth of research examining treatment efficacy for girls. This meta-analysis of 167 unique effect sizes from 29 studies (28,483 youth, 50% female; median age: 14) suggests that existing treatments have a medium positive effect on DBP (g = .33). For both boys and girls, the most effective interventions included (a) multimodal or group format, (b) cognitive skills or family systems interventions, and (c) length-intensive programs for (d) younger children. Boys demonstrated significantly greater treatment gains from group format interventions compared to girls, which is particularly important given that the group program format was the most prevalent format for boys and girls, with 14 studies involving 10,433 youth encompassing this category. This is the first meta-analysis to examine the effect of program characteristics in a sample of programs selected to be specifically inclusive of girls. Given that girls are underrepresented in intervention research on DBP, findings are discussed in terms of gender-responsive considerations and elucidating how key aspects of program structure can support more effective intervention outcomes for youth.

Brainstem gliomas in pregnancy: a systematic review†.

Introduction: Although brainstem gliomas are a rare group of neoplasias, when they affect pregnant women, there can be challenges with diagnosis and management. This study describes a case of brainstem glioma diagnosed in pregnancy and systematically reviews the literature on brainstem gliomas in pregnancy to provide guidance for management.Material and methods: We searched five databases from inception until October 2016 using subject headings and keywords related to pregnancy and brainstem glioma, and included original research articles that described pregnancy outcomes in women with brainstem glioma. Data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Checklist for case reports were performed in duplicate. Outcomes were reported as proportions. The study protocol was registered with the Prospero International Prospective Register of Systematic Reviews (CRD42017060196).Results: We screened 2737 titles and abstracts, and 89 full-texts. Twelve articles describing 17 pregnancies in 16 women were included in the analysis. The median gestational age at presentation was 23 weeks. All but one case presented with neurologic deficit. Magnetic resonance (MRI) imaging conclusively diagnosed all cases. Surgical tumor resection (n = 4) and radiation therapy (n = 3) were successfully undertaken during pregnancy. There were no reported sequelae of maternal oncological management on neonatal wellbeing. Maternal mortality was high (8/16, 50%) both during (n = 5) and within 4 weeks (n = 3) of pregnancy. Pregnancy losses included one pregnancy termination and four miscarriages (associated with maternal mortality). Of the 12 live-born babies, five were premature. Two of these were the result of spontaneous preterm labor and three were delivered prematurely to facilitate glioma management. There was one case of fetal growth restriction.Conclusions: Although the symptoms of brainstem gliomas often mimic those commonly encountered in pregnancy, neurologic deficits warrant urgent investigation. MRI is the diagnostic modality of choice in pregnancy. Brainstem gliomas are associated with high maternal mortality and appropriate management, including surgical tumor resection and radiation therapy, should not be delayed on account of pregnancy. Pregnancy outcomes are favorable although there is a risk of preterm birth.Key messageBrainstem gliomas are associated with high maternal mortality and timely diagnosis using magnetic resonance imaging and treatment including surgical resection and radiation therapy should not be delayed during pregnancy. Pregnancy outcomes are generally favorable except for risk of preterm birth.