Mean-field interacting multi-type birth-death processes with a view to applications in phylodynamics.

Multi-type birth-death processes underlie approaches for inferring evolutionary dynamics from phylogenetic trees across biological scales, ranging from deep-time species macroevolution to rapid viral evolution and somatic cellular proliferation. A limitation of current phylogenetic birth-death models is that they require restrictive linearity assumptions that yield tractable message-passing likelihoods, but that also preclude interactions between individuals. Many fundamental evolutionary processes - such as environmental carrying capacity or frequency-dependent selection - entail interactions, and may strongly influence the dynamics in some systems. Here, we introduce a multi-type birth-death process in mean-field interaction with an ensemble of replicas of the focal process. We prove that, under quite general conditions, the ensemble's stochastically evolving interaction field converges to a deterministic trajectory in the limit of an infinite ensemble. In this limit, the replicas effectively decouple, and self-consistent interactions appear as nonlinearities in the infinitesimal generator of the focal process. We investigate a special case that is rich enough to model both carrying capacity and frequency-dependent selection while yielding tractable message-passing likelihoods in the context of a phylogenetic birth-death model.

Research Review: Pharmacological and non-pharmacological treatments for adolescents with attention deficit/hyperactivity disorder - a systematic review of the literature.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) demonstrates unique developmental manifestations in adolescence with implications for optimized, age-appropriate treatment. This 10-year update is the third in a series of systematic reviews examining the efficacy and safety of adolescent ADHD treatments. We broadly examined efficacy on ADHD symptoms, impairments, and other reported outcomes. Acute and long-term efficacy, and treatment moderators, were considered. METHOD: We performed PubMed, EMBASE, and PsycINFO searches for articles published or in press from 2013 to 2024, integrated with hand search and randomized controlled trials (RCTs) identified in this series' earlier reviews. RCTs examining the safety or efficacy of interventions delivered to adolescents (ages 10.0-19.9) with a diagnosis of ADHD were included. Study characteristics were extracted and reviewed, quality of evidence was assessed using GRADE, and effect sizes were calculated for individual studies and illustrated using forest plots. RESULTS: Sixty-three RCTs were identified. Quality of evidence ranged from high (medication; k = 29) to very low (nutrient supplementation, neurofeedback, occupational therapy; k = 1 each). Medications demonstrated consistent strong impact on ADHD symptoms and inconsistent impact on impairment. Diverse cognitive/behavioral treatments (C/BTs) demonstrated inconsistent impact on ADHD symptoms but strong and consistent impact on impairment and executive function skills, plus moderate benefits on internalizing symptoms. No interventions demonstrated significant safety concerns. Long-term maintenance (up to 3 years post-treatment) was demonstrated for C/BTs, though moderate quality of evidence was noted because participants cannot be fully blinded to receipt of treatment. CONCLUSIONS: The effects of C/BTs and medication appear complementary, not duplicative. Combining medication and C/BT is advised at treatment outset to maximize engagement, maintenance, and response breadth (i.e. improving both ADHD symptoms/cognitive performance and coping skills/functional impairments). Engagement strategies (e.g. motivational interviewing) may facilitate uptake. Novel treatments do not yet demonstrate effects on ADHD symptoms or impairments in adolescents but remain a promising area for research.

Effects of aerobic exercise on neurocognitive function in postmenopausal women receiving endocrine therapy for breast cancer: The Exercise Program in Cancer and Cognition randomized controlled trial.

Objective: The Exercise Program in Cancer and Cognition (EPICC) Study was a randomized controlled trial (RCT) designed to determine whether six months of moderate-intensity aerobic exercise improves neurocognitive function in women with breast cancer (BC) receiving endocrine therapy (ET). Methods: Postmenopausal women with hormone receptor+, early-stage BC, within two years post-primary therapy were randomized to the exercise intervention (six months, ≥150 minutes of moderate-intensity aerobic exercise/week) or usual care control condition. Outcomes were assessed at pre-randomization and after intervention completion. Groups were compared using linear mixed-effects modeling. Results: Participants (N=153) were X ¯ = 62.09 ± 8.27 years old, with stage I BC (64.1%) and a median of 4.7 months post-diagnosis. We found a group-by-time interaction (p=0.041) and a trend for the main effect of time (p=0.11) for processing speed with improved performance in the exercise group and no change in the controls. Similar main effects of time were observed for learning and memory (p=0.024) and working memory (p=0.01). Better intervention adherence was associated with improved processing speed (p=0.017). Conclusions: Six months of moderate-intensity aerobic exercise improves processing speed in postmenopausal women with BC receiving ET who initiate exercise within two years of completing primary therapy (surgery +/- chemotherapy). This is the first large-scale study to examine the effects of aerobic exercise on neurocognitive function in women with BC. Additional research is needed to address the long-term effects of aerobic exercise on cognitive function.

Effects of Compliance to a Training Intervention for High School Students with ADHD.

OBJECTIVE: We evaluated the effects of treatment compliance with the Challenging Horizons Program (CHP) for high school aged adolescents with attention-deficit hyperactivity disorder (ADHD). METHOD: Participants were 185 high school aged adolescents (65% non-Hispanic White; 79% male) with a diagnosis of ADHD who were randomly assigned to either CHP or community control. Outcomes included parent-rated academic functioning, parent- and self-rated social-emotional functioning, and GPA. The complier average causal effect (CACE) was estimated using propensity-weighted models for youth engaging in ≥ 30 CHP individual sessions (15-20 min) across the academic year. RESULTS: Most (78%) CHP participants engaged in≥30 CHP sessions. CACE analyses using latent growth curve modeling revealed significant treatment effects among treatment compliers across ratings of academic and social outcomes relative to similar control participants. For most outcomes, CACE estimates were larger than those found in intent-to-treat analyses, especially at 6-months follow-up. CONCLUSIONS: Compliance with 30 or more individual CHP sessions appeared to be an attainable threshold associated with incremental gains across several academic and social outcomes. Effects of compliance were amplified at 6-months follow-up, supporting the hypothesized theory of change of training interventions. Future work should focus on facilitators of treatment engagement and feasibility of the CHP as delivered by high school personnel.

Cost-Effectiveness of a Training Intervention for Adolescents with ADHD.

OBJECTIVE: The aim of this study was to examine the costs and cost-effectiveness of a school-based training intervention delivered at varying levels of intensity with adolescents with attention-deficit/hyperactivity disorder (ADHD). Costs were examined in relation to post-treatment and 6-month follow-up effects of the Challenging Horizons Program (CHP), a training intervention for adolescents with ADHD. METHOD: A total of 326 middle-school students (71% male; 77% White) with ADHD were randomized to an after-school version of the CHP (CHP-AS), a less-intensive mentoring version (CHP-M), or routine community care. Detailed time logs were maintained throughout the study and were used to estimate costs associated with each condition. Student grade point average (GPA) and parent-rated ADHD symptoms and organization skills were collected at post-treatment and 6-month follow-up. RESULTS: The cost analysis revealed that CHP-AS was more costly per student than CHP-M, both in terms of overall costs and direct expenses to the school. However, CHP-AS was less costly per hour of intervention provided to the youth than CHP-M. Incremental cost-effectiveness ratios revealed that CHP-M may be the more cost-effective option for post-treatment effects, yet CHP-AS may be the more cost-effective option in the long term for sustained gains in organization skills and GPA. CONCLUSIONS: This study provides stakeholders important information to make decisions regarding allocation of finite monetary resources to meet their prioritized goals.

Social Functioning Outcomes of a High School-Based Treatment Program for Adolescents with ADHD.

OBJECTIVE: We evaluated the extent to which receiving the multi-component treatment of the Challenging Horizons Program (CHP) would lead to significant improvements in social functioning, as well as in inattention, internalizing symptoms, parent stress, and emotion dysregulation for high-school-aged adolescents with attention-deficit hyperactivity disorder (ADHD). METHOD: Participants were 186 high-school-aged adolescents (74% White) with a diagnosis of ADHD who were randomly assigned to either CHP (n = 92; 80% boys; M age = 15.0; SD = 0.8) or Community Care (CC; n = 94; 78% boys; M age = 15.1; SD = 0.9) within each of 12 participating schools. Parent and adolescent reports of social functioning were the primary outcome measures. Secondary outcomes included ratings of symptoms of ADHD and related disorders, parent stress, and emotion regulation. RESULTS: Intent-to-treat analyses using hierarchical linear modeling revealed significant group-by-time interactions of medium magnitude (d range = .40 to .52) on parent-rated social skills. Significant group-by-time benefits were also identified for adolescent self-rated social skills as well as the secondary outcomes of parent-rated inattention symptoms, emotion regulation, and parenting stress. DISCUSSION: CHP appears to benefit social skills along with related characteristics for adolescents with ADHD. Understanding these unique findings for this population informs additional research related to treatment mechanisms and effectiveness trials.

Bioindustrial manufacturing readiness levels (BioMRLs) as a shared framework for measuring and communicating the maturity of bioproduct manufacturing processes.

Readiness level (RL) frameworks such as technology readiness levels and manufacturing readiness levels describe the status of a technology/manufacturing process on its journey from initial conception to commercial deployment. More importantly, they provide a roadmap to guide technology development and scale-up from a ''totality of system'' approach. Commercialization risks associated with too narrowly focused R&D efforts are mitigated. RLs are defined abstractly so that they can apply to diverse industries and technology sectors. However, differences between technology sectors make necessary the definition of sector specific RL frameworks. Here, we describe bioindustrial manufacturing readiness levels (BioMRLs), a classification system specific to bioindustrial manufacturing. BioMRLs will give program managers, investors, scientists, and engineers a shared vocabulary for prioritizing goals and assessing risks in the development and commercialization of a bioindustrial manufacturing process.

Promoting Classroom Social and Academic Functioning among Children at Risk for ADHD: The MOSAIC Program.

OBJECTIVE: Social and academic functioning are linked in elementary school, and both are frequently impaired in children with elevated symptoms of attention-deficit/hyperactivity disorder (ADHD). This study evaluated the Making Socially Accepting Inclusive Classrooms (MOSAIC) program, a classroom intervention to support children's social and academic functioning, especially for children at risk for ADHD. Teachers delivered MOSAIC practices to the whole class and applied some strategies more frequently to target children selected for elevated ADHD symptoms and peer impairment. METHOD: Participants were 34 general education teachers (grades K-5) and 558 children in their classrooms, randomized to MOSAIC or to a typical practice control group for one academic year. In the fall and spring, we assessed (a) peers' sociometric judgments of children, (b) children's self-report of supportive relationships with teachers and peers, and (c) teachers' report of children's social and academic competencies and impairments. RESULTS: Regarding whole class effects, relative to control group children, children in MOSAIC classrooms (target and non-target children) were rated by teachers in spring as having better competencies and lower impairment, after controlling for fall functioning. There were no main effects of MOSAIC on peer sociometrics or child perceptions of supportive relationships. Target status moderated some effects such that, in spring, target children in MOSAIC perceived greater support from their teachers but received poorer sociometrics than did target children in control classrooms. CONCLUSIONS: We discuss the difficulty in changing peers' perceptions of children with ADHD symptoms, even in the presence of improvements in other aspects of social and academic functioning.

Disparities in Access to Postmastectomy Breast Reconstruction: Does Living in a Specific ZIP Code Determine the Patient's Reconstructive Journey?

BACKGROUND: Postmastectomy breast reconstruction (BR) has been shown to provide long-term quality of life and psychosocial benefits. Despite the policies initiated to improve access to BR, its delivery continues to be inequitable, suggesting that barriers to access have not been fully identified and/or addressed. The purpose of this study was to assess the influence of geographic location, socioeconomic status, and race in access to immediate BR (IBR). METHODS: An institutional review board-approved observational study was conducted. All patients who underwent breast cancer surgery from 2014 to 2019 were queried from our institutional Breast Cancer Registry. A geographical analysis was conducted using demographic characteristics and patient's ZIP codes. Euclidean distance from patient home ZIP code to UPMC Magee Women's Hospital was calculated, and χ2, Student t test, Mann-Whitney, and Kruskal-Wallis tests was used to evaluate differences between groups, as appropriate. Statistical significance was set at P < 0.05. RESULTS: Overall, 5835 patients underwent breast cancer surgery. A total of 56.7% underwent lumpectomy or segmental mastectomy, and 43.3% underwent modified, total, or radical mastectomy. From the latter group, 33.5% patients pursued BR at the time of mastectomy: 28.6% autologous, 48.1% implant-based, 19.4% a combination of autologous and implant-based, and 3.9% unspecified reconstruction. Rates of IBR varied among races: White or European (34.1%), Black or African American (27.7%), and other races (17.8%), P = 0.022. However, no difference was found between type of BR among races (P = 0.38). Moreover, patients who underwent IBR were significantly younger than those who did not pursue reconstruction (P < 0.0001). Patients who underwent reconstruction resided in ZIP codes that had approximately US $2000 more annual income, a higher percentage of White population (8% vs 11% non-White) and lower percentage of Black or African American population (1.8% vs 2.9%) than the patients who did not undergo reconstruction. CONCLUSIONS: While the use of postmastectomy BR has been steadily rising in the United States, racial and socioeconomic status disparities persist. Further efforts are needed to reduce this gap and expand the benefits of IBR to the entire population without distinction.

Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis.

OBJECTIVE: Platinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers. METHODS: In this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival. RESULTS: Of 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 µg/ml (range 0.4-3.1). Cisplatin LC50's correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46-1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p < 0.001). CONCLUSIONS: Metabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors.

Physical activity, cardiorespiratory fitness, and cognitive function in postmenopausal women with breast cancer.

Physical activity may improve cognitive function in women with breast cancer. In a cross-sectional study, we explored the relationship between cognitive function and physical activity (actigraph) and cardiorespiratory fitness (sub-maximal graded exercise test) in 73 postmenopausal women with early stage breast cancer prior to the initiation of systemic adjuvant therapy. Cognitive function was assessed with a standardized battery of neurocognitive measures assessing eight domains. Data were analyzed using partial correlations, controlling for age and total hours of actigraph wear-time. Women were, on average, 63.71 (± 5.3) years of age with 15.47 (± 2.48) years of education. For physical activity, greater average number of steps per day were associated with better attention (r = .262, p = .032) and psychomotor speed (r = .301, p = .011); greater average hours of moderate and moderate/vigorous intensity physical activity were associated with better visual memory (r = .241, p = .049; r = .241, p = .049, respectively); and greater average daily energy expenditure was associated with better visual memory (r = .270, p = .027) and psychomotor speed (r = .292, p = .017). For fitness, higher peak maximum VO2 was associated with better concentration (r = .330, p = .006), verbal memory (r = .241, p = .048), and working memory (r = .281, p = .019). These results suggest that higher levels of physical activity and cardiorespiratory fitness are associated with better cognitive function in postmenopausal women with breast cancer. Randomized controlled trials (RCT) to examine whether physical activity improves cognitive function in women with breast cancer are warranted. These RCTs should also determine the mechanisms of the influence of physical activity on cognitive function. CLINICAL TRIALS REGISTRATION NUMBER: NCT02793921; Date: May 20, 2016.

Randomized Trial of Academic Training and Medication Decision-Making for Adolescents with ADHD in Usual Care.

Objective: This study tested two family-based interventions designed for delivery in usual care: Changing Academic Support in the Home for Adolescents with ADHD (CASH-AA), containing motivational interventions, homework management and schoolwork organization training, and family-school partnership building; and Medication Integration Protocol (MIP), containing ADHD psychoeducation, medication decision-making, and integrated medication management.Method: This study used a cluster randomized design to test CASH-AA + MIP versus CASH-AA Only for adolescents with ADHD in five sites. Therapists (N = 49) were site clinicians randomized to condition. Clients (N = 145) included 72% males; 42% White Non-Hispanic, 37% Hispanic American, 15% African American, and 6% more than one race; average age was 14.8 years. Fidelity data confirmed protocol adherence and between-condition differentiation.Results: One-year improvements were observed across conditions in several outcomes. Overall, CASH-AA + MIP produced greater declines in adolescent-report inattentive symptoms and delinquent acts. Similarly, among non-substance users, CASH-AA + MIP clients attended more treatment sessions. In contrast, among substance users, CASH-AA Only clients showed greater declines in caregiver-report hyperactive symptoms and externalizing.Conclusions: This study provides initial experimental support for family-based ADHD medication decision-making when coupled with academic training in usual care. The treatment protocols, CASH-AA and MIP, showed positive effects in addressing not only ADHD symptoms but also common co-occurring problems, and youth with substance use problems benefitted along with non-using peers.

Community-Based Prevalence of Externalizing and Internalizing Disorders among School-Aged Children and Adolescents in Four Geographically Dispersed School Districts in the United States.

The Project to Learn About Youth-Mental Health (PLAY-MH; 2014-2018) is a school-based, two-stage study designed to estimate the prevalence of selected mental disorders among K-12 students in four U.S.-based sites (Colorado, Florida, Ohio, and South Carolina). In Stage 1, teachers completed validated screeners to determine student risk status for externalizing or internalizing problems or tics; the percentage of students identified as being at high risk ranged from 17.8% to 34.4%. In Stage 2, parents completed a structured diagnostic interview to determine whether their child met criteria for fourteen externalizing or internalizing disorders; weighted prevalence estimates of meeting criteria for any disorder were similar in three sites (14.8%-17.8%) and higher in Ohio (33.3%). PLAY-MH produced point-in-time estimates of mental disorders in K-12 students, which may be used to supplement estimates from other modes of mental disorder surveillance and inform mental health screening and healthcare and educational services.

Future Directions for Psychosocial Interventions for Children and Adolescents with ADHD.

Multiple psychosocial interventions are efficacious for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) including behavioral parent training, behavioral classroom management, behavioral peer interventions, and organization training programs. Unfortunately, there is a significant gap between research and practice such that evidence-based treatments often are not implemented in community and school settings. Using a life course model for ADHD treatment implementation, we discuss future research directions that support movement from the current, fragmented system of care to a more comprehensive, integrated, and multisystemic approach. Specifically, we offer six recommendations for future research. Within the realm of treatment development and evaluation, we recommend (1) identifying and leveraging mechanisms of change, (2) examining impact of youth development on treatment mechanisms and outcomes, and (3) designing intervention research in the context of a life course model. Within the realm of implementation and dissemination, we recommend investigating strategies to (4) enhance access to evidence-based treatment, (5) optimize implementation fidelity, and (6) examine and optimize costs and cost-effectiveness of psychosocial interventions. Our field needs to go beyond short-term, efficacy trials to reduce symptomatic behaviors conducted under ideal controlled conditions and successfully address the research-to-practice gap by advancing development, evaluation, implementation, and dissemination of evidence-based treatment strategies to ameliorate ADHD-related impairment that can be used with fidelity by parents, teachers, and community health providers.

CCR2/CCR5-mediated macrophage-smooth muscle cell crosstalk in pulmonary hypertension.

Macrophages are major players in the pathogenesis of pulmonary arterial hypertension (PAH).To investigate whether lung macrophages and pulmonary-artery smooth muscle cells (PASMCs) collaborate to stimulate PASMC growth and whether the CCL2-CCR2 and CCL5-CCR5 pathways inhibited macrophage-PASMC interactions and PAH development, we used human CCR5-knock-in mice and PASMCs from patients with PAH and controls.Conditioned media from murine M1 or M2 macrophages stimulated PASMC growth. This effect was markedly amplified with conditioned media from M2 macrophage/PASMC co-cultures. CCR2, CCR5, CCL2 and CCL5 were upregulated in macrophage/PASMC co-cultures. Compared to inhibiting either receptor, dual CCR2 and CCR5 inhibition more strongly attenuated the growth-promoting effect of conditioned media from M2-macrophage/PASMC co-cultures. Deleting either CCR2 or CCR5 in macrophages or PASMCs attenuated the growth response. In mice with hypoxia- or SUGEN/hypoxia-induced PH, targeting both CCR2 and CCR5 prevented or reversed PH more efficiently than targeting either receptor alone. Patients with PAH exhibited CCR2 and CCR5 upregulation in PASMCs and perivascular macrophages compared to controls. The PASMC growth-promoting effect of conditioned media from M2-macrophage/PASMC co-cultures was greater when PASMCs from PAH patients were used in the co-cultures or as the target cells and was dependent on CCR2 and CCR5. PASMC migration toward M2-macrophages was greater with PASMCs from PAH patients and was attenuated by blocking CCR2 and CCR5.CCR2 and CCR5 are required for collaboration between macrophages and PASMCs to initiate and amplify PASMC migration and proliferation during PAH development. Dual targeting of CCR2 and CCR5 may hold promise for treating human PAH.

A molecular war: convergent and ontogenetic evidence for adaptive host manipulation in related parasites infecting divergent hosts.

Mermithids (phylum Nematoda) and hairworms (phylum Nematomorpha) somehow drive their arthropod hosts into water, which is essential for the worms' survival after egression. The mechanisms behind this behavioural change have been investigated in hairworms, but not in mermithids. Establishing a similar mechanistic basis for host behavioural change between these two distantly related parasitic groups would provide strong convergent evidence for adaptive manipulation and insight into how these parasites modify and/or create behaviour. Here, we search for this convergence, and also contrast changes in physiology between hosts infected with immature and mature mermithids to provide the first ontogenetic evidence for adaptive manipulation by disentangling host response and pathology from the parasite's apparent manipulative effects. We used SWATH-mass spectrometry on brains of Forficula auricularia (earwig) and Bellorchestia quoyana (sandhopper), infected with the mermithids Mermis nigrescens and Thaumamermis zealandica, respectively, at both immature and mature stages of infection, to quantify proteomic changes resulting from mermithid infection. Across both hosts (and hairworm-infected hosts, from earlier studies), the general function of dysregulated proteins was conserved. Proteins involved in energy generation/mobilization were dysregulated, corroborating reports of erratic/hyperactive behaviour in infected hosts. Dysregulated proteins involved in axon/dendrite and synapse modulation were also common to all hosts, suggesting neuronal manipulation is involved in inducing positive hydrotaxis. Furthermore, downregulation of CamKII and associated proteins suggest manipulation of memory also contributes to the behavioural shift.

Let's go swimming: mermithid-infected earwigs exhibit positive hydrotaxis.

Certain species of parasites have the apparent ability to alter the behaviour of their host in order to facilitate the completion of their own life cycle. While documented in hairworms (phylum Nematomorpha), the ability for mermithid parasites (from the sister phylum Nematoda) to force hosts to enter water remains more enigmatic. Here, we present the first experimental evidence in a laboratory setting that an insect which normally never enters open water (the European earwig Forficula auricularia) will readily enter the water when infected with a mermithid nematode (Mermis nigrescens). Only adult mermithids appear capable of inducing this polarising shift in behaviour, with mermithid length being a very strong predictor of whether their host enters water. However, mermithid length was only weakly associated with how long it took an earwig to enter water following the beginning of a trial. Considering the evidence presented here and its alignment with a proteomic investigation on the same host-parasite system, this study provides strong evidence for adaptive behavioural manipulation and a foundational system for further behavioural and mechanistic exploration.

Trajectories of Global Self-Worth in Adolescents with ADHD: Associations with Academic, Emotional, and Social Outcomes.

Resilience models suggest that there are likely to be multiple trajectories of self-worth and that despite experiencing impairment, some youth with attention deficit/hyperactivity disorder (ADHD) may maintain a positive self-worth, which could buffer them against negative outcomes. The present study used a cohort-sequential longitudinal design to evaluate developmental trajectories of global self-worth in a sample of 324 middle-school-age adolescents (71% male) diagnosed with ADHD between ages 11 and 14 in predicting outcomes at age 15. Sex, medication status, and ADHD/oppositional defiant disorder symptom severity were included as covariates in the models. Using growth mixture modeling, 3 distinct self-worth trajectory groups were identified: (a) high and increasing (44.4% of participants), (b) moderate and decreasing (48.8%), and (c) low and decreasing (6.8%). Participants with high and increasing global self-worth were less likely to exhibit co-occurring depressive symptoms and had better social functioning and higher grades at age 15 relative to those in either decreasing trajectory. Implications of these findings for monitoring and supporting positive global self-worth for adolescents with ADHD are discussed.

Exploring how adolescents with ADHD use and interact with technology.

INTRODUCTION: The ubiquity of technology is reshaping the way teens express themselves and interact with peers. Considering that teens with attention-deficit/hyperactivity disorder (ADHD) experience a range of social impairments and that risk behaviors have the potential to be more widespread and damaging online, understanding how teens with ADHD use the Internet is important. METHODS: The current study included 58 teens (72.4% boys; 13-16 years old) from the United States of America with ADHD. Study aims were to examine these teens' Internet use frequency, preferred online activities, Facebook interactions, and online risk behaviors (i.e., cyberbullying and sexting). Associations between online behaviors and offline symptoms and behaviors were explored to identify potential risk and protective factors. RESULTS: Findings suggested that teens with ADHD use technology in similar ways as do the general population of teens described in previous research but appeared at unique risk of cyberbullying behaviors. Offline risks were associated with online risk behaviors. Using Facebook was associated with online risks (e.g., weak online connections) and offline risks (e.g., poorer social skills and more internalizing symptoms). CONCLUSIONS: Online social platforms permit the exploration of social behaviors via naturalistic observation. It is imperative researchers gain understanding of the increasingly prevalent online social worlds of teens. Such an understanding may enable researchers to formulate effective social interventions for teens with ADHD.

MARKOV PROCESSES CONDITIONED ON THEIR LOCATION AT LARGE EXPONENTIAL TIMES.

Suppose that (Xt ) t ≥0 is a one-dimensional Brownian motion with negative drift -µ. It is possible to make sense of conditioning this process to be in the state 0 at an independent exponential random time and if we kill the conditioned process at the exponential time the resulting process is Markov. If we let the rate parameter of the random time go to 0, then the limit of the killed Markov process evolves like X conditioned to hit 0, after which time it behaves as X killed at the last time X visits 0. Equivalently, the limit process has the dynamics of the killed "bang-bang" Brownian motion that evolves like Brownian motion with positive drift +µ when it is negative, like Brownian motion with negative drift -µ when it is positive, and is killed according to the local time spent at 0. An extension of this result holds in great generality for a Borel right process conditioned to be in some state a at an exponential random time, at which time it is killed. Our proofs involve understanding the Campbell measures associated with local times, the use of excursion theory, and the development of a suitable analogue of the "bang-bang" construction for a general Markov process. As examples, we consider the special case when the transient Borel right process is a one-dimensional diffusion. Characterizing the limiting conditioned and killed process via its infinitesimal generator leads to an investigation of the h-transforms of transient one-dimensional diffusion processes that goes beyond what is known and is of independent interest.