Faculty Bibliography

We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber with a fiducial mass of (1.30±0.01)  ton, resulting in a 1.0 ton yr exposure. The energy region of interest, [1.4,10.6]  keV_{ee} ([4.9,40.9] keV_{nr}), exhibits an ultralow electron recoil background rate of [82_{-3}^{+5}(syst)±3(stat)]  events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6  GeV/c^{2}, with a minimum of 4.1×10^{-47}  cm^{2} at 30  GeV/c^{2} and a 90% confidence level.

Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act as a scavenger by effectively increasing the levels of NAGS, ultimately enhancing the conversion of ammonia to urea. In our case report, we have mentioned a patient with treatment-resistant bipolar disorder, who presented with elevated ammonia levels secondary to valproic acid treatment. Valproic acid was the only drug that was effective in his case, so we initiated therapy to reduce his elevated ammonia levels. After a thorough evaluation, we found the patient had a genetic NAGS deficiency. Carglumic acid was initiated and proved efficacious in our patient.

Background Infants with critical congenital heart disease ( CCHD ) are more likely to be small for gestational age (GA). It is unclear how this affects mortality. The authors investigated the effect of birth weight Z score on 1-year mortality separately in preterm (GA <37 weeks), early-term (GA 37-38 weeks), and full-term (GA 39-42 weeks) infants with CCHD . Methods and Results Live-born infants with CCHD and GA 22 to 42 weeks born in California 2007-2012 were included in the analysis. The primary predictor was Z score for birth weight and the primary outcome was 1-year mortality. Multivariable logistic regression was used. Results are presented as adjusted odds ratios and 95% confidence intervals ( CIs ). The authors identified 6903 infants with CCHD . For preterm and full-term infants, only a Z score for birth weight <-2 was associated with increased mortality compared with the reference group ( Z score 0-0.5, adjusted odds ratio, 2.15 [95% CI , 1.1-4.21] and adjusted odds ratio, 3.93 [95% CI , 2.32-6.68], respectively). In contrast, in early-term infants, the adjusted odds ratios for Z scores <-2, -2 to -1, and -1 to -0.5 were 3.42 (95% CI , 1.93-6.04), 1.78 (95% CI , 1.12-2.83), and 2.03 (95% CI , 1.27-3.23), respectively, versus the reference group. Conclusions GA seems to modify the effect of birth weight Z score on mortality in infants with CCHD . In preterm and full-term infants, only the most severe small-for-GA infants ( Z score <-2) were at increased risk for mortality, while, in early-term infants, the risk extended to mild to moderate small-for-GA infants ( Z score <-0.5). This information helps to identify high-risk infants and is useful for surgical planning.

Background Post-traumatic stress disorder (PTSD) is prevalent in children, adolescents and adults. It can occur alone or in comorbidity with other disorders. A broad range of psychotherapies such as cognitive behavioral therapy (CBT) and eye movement desensitization and reprocessing (EMDR) have been developed for the treatment of PTSD. Aim Through quantitative meta-analysis, we aimed to compare the efficacy of CBT and EMDR: (i) relieving the post-traumatic symptoms, and (ii) alleviating anxiety and depression, in patients with PTSD. Methods We systematically searched EMBASE, Medline and Cochrane central register of controlled trials (CENTRAL) for articles published between 1999 and December 2017. Randomized clinical trials (RCTs) that compare CBT and EMDR in PTSD patients were included for quantitative meta-analysis using RevMan Version 5. Results Fourteen studies out of 714 were finally eligible. Meta-analysis of 11 studies (n = 547) showed that EMDR is better than CBT in reducing post-traumatic symptoms [SDM (95% CI) = -0.43 (-0.73 - -0.12), p = 0.006]. However, meta-analysis of four studies (n = 186) at three-month follow-up revealed no statistically significant difference [SDM (95% CI) = -0.21 (-0.50 - 0.08), p = 0.15]. The EMDR was also better than CBT in reducing anxiety [SDM (95% CI) = -0.71 (-1.21 - -0.21), p = 0.005]. Unfortunately, there was no difference between CBT and EMDR in reducing depression [SDM (95% CI) = -0.21 (-0.44 - 0.02), p = 0.08]. Conclusion The results of this meta-analysis suggested that EMDR is better than CBT in reducing post-traumatic symptoms and anxiety. However, there was no difference reported in reducing depression. Large population randomized trials with longer follow-up are recommended to build conclusive evidence.

What incites infant locomotion? Recent research suggests that locomotor exploration is not primarily directed toward distant people, places, or things. However, this question has not been addressed experimentally. In the current study, we asked whether a room filled with toys designed to encourage locomotion (stroller, ball, etc.) elicits different quantities or patterns of exploration than a room with no toys. Caregivers were present but did not interact with infants. Although most walking bouts in the toy-filled room involved toys, to our surprise, 15-month-olds in both rooms produced the same quantity of locomotion. This finding suggests that mere space to move is sufficient to elicit locomotion. However, infants' patterns of locomotor exploration differed: Infants in the toy-filled room spent a smaller percent of the session within arms' reach of their caregiver and explored more locations in the room. Real-time analyses show that infants in the toy-filled room took an increasing number of steps per bout and covered more area as the session continued, whereas infants in the no-toy room took fewer and fewer steps per bout and traveled repeatedly over the same ground. Although not required to elicit locomotion, moving with toys encouraged infants to travel farther from their caregivers and to explore new areas.

The fifth edition of the Diagnostic and Statistical Manual ( DSM) categorizes reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) as two separate disorders, and their criteria are revised. For DSED, the core symptoms focus on abnormal social disinhibition, and symptoms regarding lack of selective attachment have been removed. The core symptoms of RAD are the absence of attachment behaviors and emotional dysregulation. In this study, an international team of researchers modified the Child and Adolescent Psychiatric Assessment for RAD to update it from DSM-IV to DSM-5 criteria for RAD and DSED. We renamed the interview the reactive attachment disorder and disinhibited social engagement disorder assessment (RADA). Foster parents of 320 young people aged 11 to 17 years completed the RADA online. Confirmatory factor analysis of RADA items identified good fit for a three-factor model, with one factor comprising DSED items (indiscriminate behaviors with strangers) and two factors comprising RAD items (RAD1: failure to seek/accept comfort, and RAD2: withdrawal/hypervigilance). The three factors showed differential associations with clinical symptoms of emotional and social impairment. Time in foster care was not associated with scores on RAD1, RAD2, or DSED. Higher age was associated with lower scores on DSED, and higher scores on RAD1.

Objective:Given the increased risk for cognitive deficits and development of depressive symptoms in youth with spina bifida (SB), this study aimed to examine two pathways through which depressive symptoms and neuropsychological dysfunction may be associated with medical autonomy in this population: (1) depressive symptoms as predictors of medical autonomy as mediated by attention/executive functioning (the cognitive scarring model), and (2) attention/executive functioning as predictors of medical autonomy as mediated by depressive symptoms (the cognitive vulnerability model). Methods:Participants were recruited as part of a larger, longitudinal study, and included 114 youth with SB (M age = 10.96 at Time 1), their parents, and teachers. Neuropsychological constructs included attention, working memory, and planning/organizing abilities, which were measured with questionnaire and performance-based data. Depressive symptoms and medical responsibility were assessed via questionnaires from multiple respondents. Results:Bootstrapped mediation analyses revealed that teacher-reported depressive symptoms significantly mediated the relations between neuropsychological functioning (i.e., attention and working memory) and medical responsibility (all p's < .05); neuropsychological dysfunction did not mediate the relationship between depressive symptoms and medical responsibility. Conclusions:One way in which neurocognitive dysfunction may hinder the development of medical autonomy in youth with SB is through an increased risk for depressive symptoms.

Relatively poor treatment outcomes have been reported for children with conduct problems (CPs) and high levels of callous-unemotional (CU) traits (e.g., a lack of guilt, a lack of empathy, shallow affect), yet the mechanisms underlying this effect are poorly understood. Recently, growing evidence of aberrant reward/punishment processing in children with CU traits has suggested that punishment-based parenting strategies may be less effective among children with high levels of CU traits. Using a randomized controlled trial design, we conducted an experimental test of whether CU traits are associated with differential response to reward versus punishment components of evidence-based parent-training interventions for CPs. Parents of children (n = 74) 3 to 8 years of age were randomized to either 5 weeks of reward-based or 5 weeks of punishment-based parenting strategies, after which time each received the alternative intervention. Contrary to predictions, neither type nor dosage of parent training strategies was found to moderate the relation between CU traits and treatment response. Implications for the treatment of CPs in children with high levels of CU traits, and research into mechanisms of behavior change, are discussed.