Limited Benefit of Postexposure Prophylaxis With VSV-EBOV in Ebola Virus-Infected Rhesus Macaques.

Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true postexposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramuscular VSV-EBOV administration to improve PEP efficacy in the rhesus macaque model. VSV-EBOV treatment 1 hour after EBOV challenge resulted in delayed disease progression but little benefit in outcome. Thus, we could not confirm previous results indicating questionable benefit of VSV-EBOV for EBOV PEP in a nonhuman primate model.

Effect of Hearing Device Use on Speech-in-Noise Performance in Children with Severe-to-Profound Unilateral Hearing Loss.

OBJECTIVES: Limited evidence exists for the use of rerouting devices in children with severe-to-profound unilateral sensorineural hearing loss. Many laboratory studies to date have evaluated hearing-in-noise performance in specific target-masker spatial configurations within a small group of participants and with only a subset of available hearing devices. In the present study, the efficacy of all major types of nonsurgical devices was evaluated within a larger group of pediatric subjects on a challenging speech-in-noise recognition task. DESIGN: Children (7-18 years) with unaided severe-to-profound unilateral hearing loss (UHL' n = 36) or bilateral normal hearing (NH, n = 36) participated in the present study. The signal-to-noise ratio (SNR) required for 50% speech understanding (SNR-50) was measured using BKB sentences in the presence of proprietary restaurant noise (R-SPACE BSIN-R) in the R-SPACE Sound System. Subjects listened under 2 target/masker spatial configurations. The target signal was directed toward subjects' NH or hearing-impaired ear (45º azimuth), while the interfering restaurant noise masker was presented from the remaining 7 loudspeakers encircling the subject, spaced every 45º. Head position was fixed during testing. The presentation level of target sentences and masking noise varied over time to estimate the SNR-50 (dB). The following devices were tested in all participants with severe-to-profound UHL: air conduction (AC) contralateral routing of signal (CROS), bone conduction (BC) CROS fitted on a headband with and without the use of remote microphone (RM), and an ear-level RM hearing assistance technology (HAT) system. RESULTS: As a group, participants with severe-to-profound UHL performed best when the target signal was directed toward their NH ear. Across listening conditions, there was an average 8.5 dB improvement in SNR-50 by simply orienting the NH ear toward the target signal. When unaided, participants with severe-to-profound UHL performed as well as participants with NH when the target signal was directed toward the NH ear. Performance was negatively affected by AC CROS when the target signal was directed toward the NH ear, whereas no statistically significant change in performance was observed when using BC CROS. When the target signal was directed toward participants' hearing-impaired ear, all tested devices improved SNR-50 compared with the unaided condition, with small improvements (1-2 dB) observed with CROS devices and the largest improvement (9 dB) gained with the personal ear-level RM HAT system. No added benefit nor decrement was observed when RM was added to BC CROS using a 50/50 mixing ratio when the target was directed toward the impaired ear. CONCLUSIONS: In a challenging listening environment with diffuse restaurant noise, SNR-50 was most improved in the study sample when using a personal ear-level RM HAT system. Although tested rerouting devices offered measurable improvement in performance (1-2 dB in SNR-50) when the target was directed to the impaired ear, benefit may be offset by a detriment in performance in the opposing condition. Findings continue to support use of RM HAT for children with severe-to-profound UHL in adverse listening environments, when there is one primary talker of interest, to ensure advantageous SNRs.

American Cochlear Implant Alliance Task Force Guidelines for Clinical Assessment and Management of Cochlear Implantation in Children With Single-Sided Deafness.

More children with single-sided deafness (SSD) are receiving cochlear implants (CIs) due to the expansion of CI indications. This unique group of pediatric patients has different needs than the typical recipient with bilateral deafness and requires special consideration and care. The goal of cochlear implantation in these children is to provide bilateral input to encourage the development of binaural hearing. Considerations for candidacy and follow-up care should reflect and measure these goals. The purpose of this document is to review the current evidence and provide guidance for CI candidacy, evaluation, and management in children with SSD.

Incidence, Time Course, and Implications of Electrode Abnormalities in Pediatric Cochlear Implant Recipients.

OBJECTIVES: To identify the incidence of specific abnormal impedance patterns or electrode faults, and determine their implication and significance, in a pediatric population of cochlear implant recipients. DESIGN: Nine hundred fifty-six cochlear implant devices (621 recipients) were included in this retrospective study. Devices were included if the implantation surgery was performed at our tertiary care hospital, and the recipient was 21 years of age or younger at the time the device was implanted. Device models incapable of producing impedance measures by telemetry were excluded from the study. Individual devices with abnormal impedance measures indicating an open circuit (OC), short circuit (SC), or partial short circuit (partial SC) were included in the study, unless these abnormalities occurred only in the OR and not postoperatively. Device and patient characteristics were examined to determine their relationship to increased incidence of electrode faults or atypical patterns. RESULTS: The incidence of software-identified electrode faults in our exclusively pediatric population was similar to that reported in the literature containing mixed-age cohorts. Nine percent of devices experienced at least one OC or one pair of SCs. Although higher incidence of these faults was seen in some specific device models, the long-term average of these faults was equivalent across manufacturers. No factors examined in this study increased the likelihood of experiencing a software-identified electrode fault. Within the study period under examination (October 1997 to March 2018), partial SCs (presenting as zig-zag or low-flat impedance patterns) were only observed in Cochlear devices. While the incidence of these partial SC abnormalities (non-software-identified faults) was 6% across all models of Cochlear devices, the CI24RCS experienced the highest incidence of partial SCs. The incidence of this pattern was lower in models manufactured after CI24RCS. CONCLUSIONS: This study provides incidence of various cochlear implant electrode impedance abnormalities across a large cohort of pediatric recipients. The incidence of all electrode abnormalities was relatively low, particularly partial SCs, which are less well recognized and not currently identified by clinician-accessible software. Incidence of software-identified electrode faults (i.e., SCs and OCs) in our pediatric-only study is similar to the incidence reported in other mixed-population and adult-only studies. These common electrode faults generally are not associated with device failure, and clinicians should feel comfortable reassuring families that an individual electrode fault does not imply an impending device failure. Conversely, those atypical impedance patterns not currently flagged by the programming software as abnormal, but visible to the clinician's eye (i.e., partial SCs in zig-zag or low-flat patterns), have a higher likelihood of device damage and failure. Performance in patients with electrode arrays exhibiting these atypical patterns should be closely monitored for any functional decrement, and proactively managed to maintain performance whenever possible.

Diagnostic qPCR Assay to Detect Fusarium brasiliense, a Causal Agent of Soybean Sudden Death Syndrome and Root Rot of Dry Bean.

Species within clade 2 of the Fusarium solani species complex (FSSC) are significant pathogens of dry bean (Phaseolus vulgaris) and soybean (Glycine max), causing root rot and/or sudden death syndrome (SDS). These species are morphologically difficult to distinguish and often require molecular tools for proper diagnosis to a species level. Here, a TaqMan probe-based quantitative PCR (qPCR) assay was developed to distinguish Fusarium brasiliense from other closely related species within clade 2 of the FSSC. The assay displays high specificity against close relatives and high sensitivity, with a detection limit of 100 fg. This assay was able to detect F. brasiliense from purified mycelia, infected dry bean roots, and soil samples throughout Michigan. When multiplexed with an existing qPCR assay specific to Fusarium virguliforme, accurate quantification of both F. brasiliense and F. virguliforme was obtained, which can facilitate accurate diagnoses and identify coinfections with a single reaction. The assay is compatible with multiple qPCR thermal cycling platforms and will be helpful in providing accurate detection of F. brasiliense. Management of root rot and SDS pathogens in clade 2 of the FSSC is challenging and must be done proactively, because no midseason management strategies currently exist. However, accurate detection can facilitate management decisions for subsequent growing seasons to successfully manage these pathogens.

Did I Inherit My Moral Compass? Examining Socialization and Evocative Mechanisms for Virtuous Character Development.

Virtuous character development in children is correlated with parenting behavior, but the role of genetic influences in this association has not been examined. Using a longitudinal twin/sibling study (N = 720; Time 1 (T1) Mage = 12-14 years, Time 3 (T3) Mage = 25-27 years), the current report examines associations among parental negativity/positivity and offspring responsibility during adolescence, and subsequent young adult conscientiousness. Findings indicate that associations among parental negativity and offspring virtuous character during adolescence and young adulthood are due primarily to heritable influences. In contrast, the association between concurrent parental positivity and adolescent responsibility was due primarily to heritable and shared environmental influences. These findings underscore the contributions of heritable influences to the associations between parenting and virtuous character that have previously been assumed to be only environmentally influenced, emphasizing the complexity of mechanisms involved in the development of virtuous character.

Speech-in-Noise and Quality-of-Life Measures in School-Aged Children With Normal Hearing and With Unilateral Hearing Loss.

OBJECTIVES: (1) Measure sentence recognition in co-located and spatially separated target and masker configurations in school-aged children with unilateral hearing loss (UHL) and with normal hearing (NH). (2) Compare self-reported hearing-related quality-of-life (QoL) scores in school-aged children with UHL and NH. DESIGN: Listeners were school-aged children (6 to 12 yrs) with permanent UHL (n = 41) or NH (n = 35) and adults with NH (n = 23). Sentence reception thresholds (SRTs) were measured using Hearing In Noise Test-Children sentences in quiet and in the presence of 2-talker child babble or a speech-shaped noise masker in target/masker spatial configurations: 0/0, 0/-60, 0/+60, or 0/±60 degrees azimuth. Maskers were presented at a fixed level of 55 dBA, while the level of the target sentences varied adaptively to estimate the SRT. Hearing-related QoL was measured using the Hearing Environments and Reflection on Quality of Life (HEAR-QL-26) questionnaire for child subjects. RESULTS: As a group, subjects with unaided UHL had higher (poorer) SRTs than age-matched peers with NH in all listening conditions. Effects of age, masker type, and spatial configuration of target and masker signals were found. Spatial release from masking was significantly reduced in conditions where the masker was directed toward UHL subjects' normal-hearing ear. Hearing-related QoL scores were significantly poorer in subjects with UHL compared to those with NH. Degree of UHL, as measured by four-frequency pure-tone average, was significantly correlated with SRTs only in the two conditions where the masker was directed towards subjects' normal-hearing ear, although the unaided Speech Intelligibility Index at 65 dB SPL was significantly correlated with SRTs in four conditions, some of which directed the masker to the impaired ear or both ears. Neither pure-tone average nor unaided Speech Intelligibility Index was correlated with QoL scores. CONCLUSIONS: As a group, school-aged children with UHL showed substantial reductions in masked speech perception and hearing-related QoL, irrespective of sex, laterality of hearing loss, and degree of hearing loss. While some children demonstrated normal or near-normal performance in certain listening conditions, a disproportionate number of thresholds fell in the poorest decile of the NH data. These findings add to the growing literature challenging the past assumption that one ear is "good enough."

Longitudinal examination of pathways to peer problems in middle childhood: A siblings-reared-apart design.

To advance research from Dishion and others on associations between parenting and peer problems across childhood, we used a sample of 177 sibling pairs reared apart since birth (because of adoption of one of the siblings) to examine associations between parental hostility and children's peer problems when children were ages 7 and 9.5 years (n = 329 children). We extended conventional cross-lagged parent-peer models by incorporating child inhibitory control as an additional predictor and examining genetic contributions via birth mother psychopathology. Path models indicated a cross-lagged association from parental hostility to later peer problems. When child inhibitory control was included, birth mother internalizing symptoms were associated with poorer child inhibitory control, which was associated with more parental hostility and peer problems. The cross-lagged paths from parental hostility to peer problems were no longer significant in the full model. Multigroup analyses revealed that the path from birth mother internalizing symptoms to child inhibitory control was significantly higher for birth parent-reared children, indicating the possible contribution of passive gene-environment correlation to this association. Exploratory analyses suggested that each child's unique rearing context contributed to his or her inhibitory control and peer behavior. Implications for the development of evidence-based interventions are discussed.

A Longitudinal Examination of Service Utilization and Trauma Symptoms among Young Women with Prior Foster Care and Juvenile Justice System Involvement.

We investigated the prediction of young adult service utilization and trauma symptoms from adverse childhood experiences (ACEs) and adolescent mental health symptoms in young women with dual child welfare and juvenile justice system involvement. A sample of 166 females (ages 13 to 17) was followed to examine the transition to young adulthood. Path models indicated that more ACEs were associated with poorer adolescent mental health. Adolescent mental health symptoms were associated with more young adult trauma symptoms and service utilization. Implications for service providers and policy-makers are discussed.

Pathogenicity of Ebola and Marburg Viruses Is Associated With Differential Activation of the Myeloid Compartment in Humanized Triple Knockout-Bone Marrow, Liver, and Thymus Mice.

Ebola virus (EBOV) and Marburg virus (MARV) outbreaks are highly lethal, and infection results in a hemorrhagic fever with complex etiology. These zoonotic viruses dysregulate the immune system to cause disease, in part by replicating within myeloid cells that would normally innately control viral infection and shape the adaptive immune response. We used triple knockout (TKO)-bone marrow, liver, thymus (BLT) humanized mice to recapitulate the early in vivo human immune response to filovirus infection. Disease severity in TKO-BLT mice was dissimilar between EBOV and MARV with greater severity observed during EBOV infection. Disease severity was related to increased Kupffer cell infection in the liver, higher levels of myeloid dysfunction, and skewing of macrophage subtypes in EBOV compared with MARV-infected mice. Overall, the TKO-BLT model provided a practical in vivo platform to study the human immune response to filovirus infection and generated a better understanding of how these viruses modulate specific components of the immune system.

Metabolic Reprogramming of Host Cells by Virulent Francisella tularensis for Optimal Replication and Modulation of Inflammation.

A shift in macrophage metabolism from oxidative phosphorylation to aerobic glycolysis is a requirement for activation to effectively combat invading pathogens. Francisella tularensis is a facultative intracellular bacterium that causes an acute, fatal disease called tularemia. Its primary mechanism of virulence is its ability to evade and suppress inflammatory responses while replicating in the cytosol of macrophages. The means by which F. tularensis modulates macrophage activation are not fully elucidated. In this study, we demonstrate that virulent F. tularensis impairs production of inflammatory cytokines in primary macrophages by preventing their shift to aerobic glycolysis, as evidenced by the downregulation of hypoxia inducible factor 1α and failure to upregulate pfkfb3 We also show that Francisella capsule is required for this process. In addition to modulating inflammatory responses, inhibition of glycolysis in host cells is also required for early replication of virulent Francisella Taken together, our data demonstrate that metabolic reprogramming of host cells by F. tularensis is a key component of both inhibition of host defense mechanisms and replication of the bacterium.

Transactions Between Substance Use Intervention, the Oxytocin Receptor (OXTR) Gene, and Peer Substance Use Predicting Youth Alcohol Use.

This study investigated the oxytocin receptor (OXTR) gene's moderation of associations between exposure to a substance misuse intervention, average peer substance use, and adolescents' own alcohol use during the 9th-grade. OXTR genetic risk was measured using five single nucleotide polymorphisms (SNPs), and peer substance use was based on youths' nominated closest friends' own reports of alcohol, cigarette, and marijuana use, based on data from the PROSPER project. Regression models revealed several findings. First, low OXTR risk was linked to affiliating with friends who reported less substance use in the intervention condition but not the control condition. Second, affiliating with high substance-using friends predicted youth alcohol risk regardless of OXTR risk or intervention condition. Third, although high OXTR risk youth in the intervention condition who associated with low substance-using friends reported somewhat higher alcohol use than comparable youth in the control group, the absolute level of alcohol use among these youth was still among the lowest in the sample.

Can monaural temporal masking explain the ongoing precedence effect?

The precedence effect for transient sounds has been proposed to be based primarily on monaural processes, manifested by asymmetric temporal masking. This study explored the potential for monaural explanations with longer ("ongoing") sounds exhibiting the precedence effect. Transient stimuli were single lead-lag noise burst pairs; ongoing stimuli were trains of 63 burst pairs. Unlike with transients, monaural masking data for ongoing sounds showed no advantage for the lead, and are inconsistent with asymmetric audibility as an explanation for ongoing precedence. This result, along with supplementary measurements of interaural time discrimination, suggests different explanations for transient and ongoing precedence.

Twelve Steps, Two Factors: Coping Strategies Moderate the Association Between Craving and Daily 12-Step Use in a College Recovery Community.

BACKGROUND: Affiliating with 12-step groups appears to reduce relapse risk. By relying on between-person designs, extant research has been unable to examine daily mechanisms through which 12-step group affiliation contributes to recovery. OBJECTIVES: To examine the daily use and factor structure of the 12 steps and intrapersonal predictors and moderators of 12-step use. To determine whether the 12 steps were used in response to daily craving and, if so, which steps and in what contexts. METHODS: Data comprised 1304 end-of-day diary data entries from 55 young adults collected in 2008 from members of a college recovery community, combined with person-level baseline measures. Exploratory factor analysis examined the factor structure, and multi-level models examined both day-level and person-level predictors and moderators of step use, including meeting attendance, drug and alcohol dependence, social support, and coping strategies. RESULTS: Analyses produced two factors: Everyday steps, comprising surrender and maintenance steps, and action steps. Moderation analyses revealed that only action steps were significantly associated with craving, suggesting that craving can spur their use, but only among individuals pursuing certain general strategies for coping with stress: Separate median-split models produced significant associations between craving and action steps only among individuals high in avoidance, high in support-seeking, and/or low in problem-solving. Conclusions/Importance: This is the first study to empirically discern a 2-factor structure underlying the 12 steps, and to show that the two sets of steps are used in different contexts. The study also illustrates the value of person-centered approaches to recovery research and practice.

Fungal endophytes of wild and hybrid Vitis leaves and their potential for vineyard biocontrol.

Plants are colonized by diverse assemblages of fungal endophytes that have potential as biocontrol agents for a variety of crops, including grapevine. Although the diversity of symbionts can be very high in wild plants, the fungal endophytes of wild Vitis plants have not yet been investigated. We surveyed the fungal endophytes of 6 wild populations of Vitis riparia, as well as a cold-tolerant, hybrid grapevine in 5 vineyards (1 certified organic), using 454 pyrosequencing. We detected between 43 and 235 operational taxonomic units per sample, with the highest richness and diversity in the wild, the lowest in conventional vineyards, and intermediate levels in the organic vineyard. Wild plants supported a range of taxa not seen in the conventional vineyards, and vineyards were dominated by relatively few taxa. We also isolated fungi from the wild plants and tested them for their ability to inhibit pathogens of grapevine. Several wild isolates (e.g., Ramularia spp.) were strongly inhibitory to grapevine pathogens. We show that wild Vitis supports a distinct and highly diverse community of fungal endophytes and may represent a rich repository of potential vineyard biocontrol agents.

Comparison of the effectiveness of whole-brain radiotherapy plus temozolomide versus whole-brain radiotherapy in treating brain metastases based on a systematic review of randomized controlled trials.

Temozolomide (TMZ) combination with whole-brain radiotherapy (WBRT) has been tested by many randomized controlled trials in the treatment of brain metastases (BMs) in China and other countries. We performed an up-to-date meta-analysis to determine (i) the log odds ratios (LORs) of objective response (ORR) and adverse effects (AEs) for all-grade, and (ii) the T value of mean overall survival in patients with BMs treated with WBRT combined with TMZ versus WBRT alone. PubMed, Chinese National Knowledge Infrastructure, and WanFang Data were searched for articles published up to 28 January 2015. Eligible studies were selected according to the PRISMA statement. ORR, AEs, and 95% confidence intervals were calculated using random-effects models. Eighteen studies were included in our analysis. A total of 1028 participants were enrolled. Summary LORs of ORR were 1.0239 (P<0.0001) on comparing WBRT plus TMZ with WBRT ORR (n=17). The overall mean difference of mean overall survival (n=17) between TMZ plus WBRT and WBRT was 2.2505 weeks (P=0.02185). There was a significant difference between WBRT plus TMZ and WBRT alone with a LOR of AEs for all-grade of (i) 0.923 for gastrointestinal toxicity and (ii) 0.7978 for myelosuppression. Sensitivity analysis and subgroup analysis were also performed. The 18 eligible randomized controlled trials demonstrated that the combination of WBRT and TMZ significantly improves the ORR and is statistically insignificant in prolonging the survival of patients with BMs. In addition, an increase in the incidence of gastrointestinal toxicity and myelosuppression was significant for all-grade.

Contamination in the Prospective Study of Child Maltreatment and Female Adolescent Health.

OBJECTIVE: To evaluate the impact of contamination, or the presence of child maltreatment in a comparison condition, when estimating the broad, longitudinal effects of child maltreatment on female health at the transition to adulthood. METHODS: The Female Adolescent Development Study (N = 514; age range: 14-19 years) used a prospective cohort design to examine the effects of substantiated child maltreatment on teenage births, obesity, major depression, and past-month cigarette use. Contamination was controlled via a multimethod strategy that used both adolescent self-report and Child Protective Services records to remove cases of child maltreatment from the comparison condition. RESULTS: Substantiated child maltreatment significantly predicted each outcome, relative risks = 1.47-2.95, 95% confidence intervals: 1.03-7.06, with increases in corresponding effect size magnitudes, only when contamination was controlled using the multimethod strategy. CONCLUSIONS: Contamination truncates risk estimates of child maltreatment and controlling it can strengthen overall conclusions about the effects of child maltreatment on female health.

Adaptation to Parental Gender Transition: Stress and Resilience Among Transgender Parents.

Little is known about transgender parents and how they have negotiated their gender transition, referred to here as Parental Gender Transition (PGT), and subsequent stressors. This study addressed this gap using an adapted version of the ABC-X model and Family Stress Theory. The family functioning of 73 transgender parents (72.2 % born male, 25.0 % born female, and 2.8 % other, e.g., intersex), who transitioned after they had children, was examined in regard to the potential stresses associated with PGT (impact of disclosure, stigma, and boundary ambiguity), resources available to transitioning parents (social support and coping), and perception (sense of coherence and perceptions of PGT). Hierarchical multiple regression and path analysis were then conducted to determine if resources and perception altered the relationship between stress and family functioning. Findings from these transgender parents indicated an ameliorating role of sense of coherence, or the perception that they can handle the situation, on the relationship between stigma and family functioning, but not between boundary ambiguity, or confusion regarding who is in the family system, and family functioning. This suggests one avenue for professionals to intervene and help families through PGT. However, it also indicates the need for further research to determine ways to mitigate the impact of boundary ambiguity on family functioning.

B1a cells enhance susceptibility to infection with virulent Francisella tularensis via modulation of NK/NKT cell responses.

B1a cells are an important source of natural Abs, Abs directed against T-independent Ags, and are a primary source of IL-10. Bruton's tyrosine kinase (btk) is a cytoplasmic kinase that is essential for mediating signals from the BCR and is critical for development of B1a cells. Consequentially, animals lacking btk have few B1a cells, minimal Ab responses, and can preferentially generate Th1-type immune responses following infection. B1a cells have been shown to aid in protection against infection with attenuated Francisella tularensis, but their role in infection mediated by fully virulent F. tularensis is not known. Therefore, we used mice with defective btk (CBA/CaHN-Btk(XID)/J [XID mice]) to determine the contribution of B1a cells in defense against the virulent F. tularensis ssp. tularensis strain SchuS4. Surprisingly, XID mice displayed increased resistance to pulmonary infection with F. tularensis. Specifically, XID mice had enhanced clearance of bacteria from the lung and spleen and significantly greater survival of infection compared with wild-type controls. We revealed that resistance to infection in XID mice was associated with decreased numbers of IL-10-producing B1a cells and concomitant increased numbers of IL-12-producing macrophages and IFN-γ-producing NK/NKT cells. Adoptive transfer of wild-type B1a cells into XID mice reversed the control of bacterial replication. Similarly, depletion of NK/NKT cells also increased bacterial burdens in XID mice. Together, our data suggest B cell-NK/NKT cell cross-talk is a critical pivot controlling survival of infection with virulent F. tularensis.

Symptoms of major depressive disorder subsequent to child maltreatment: Examining change across multiple levels of analysis to identify transdiagnostic risk pathways.

Major depressive disorder (MDD) is a prevalent psychiatric condition in the child maltreatment population. However, not all children who have been maltreated will develop MDD or MDD symptoms, suggesting the presence of unique risk pathways that explain how certain children develop MDD symptoms when others do not. The current study tested several candidate risk pathways to MDD symptoms following child maltreatment: neuroendocrine, autonomic, affective, and emotion regulation. Female adolescents (N = 110; age range = 14-19) were recruited into a substantiated child maltreatment or comparison condition and completed a laboratory stressor, saliva samples, and measures of emotion regulation, negative affect, and MDD symptoms. MDD symptoms were reassessed 18 months later. Mediational modeling revealed that emotion regulation was the only significant indirect effect of the relationship between child maltreatment and subsequent MDD symptoms, demonstrating that children exposed to maltreatment had greater difficulties managing affective states that in turn led to more severe MDD symptoms. These results highlight the importance of emotion dysregulation as a central risk pathway to MDD following child maltreatment. Areas of future research and implications for optimizing prevention and clinical intervention through the direct targeting of transdiagnostic risk pathways are discussed.