Exploring stimulant treatment in ADHD: narratives of young adolescents and their parents

BACKGROUND: Young adolescents’ and their parents’ experiences with Attention-Deficit/Hyperactivity Disorder (ADHD) and its treatment were explored to investigate beliefs and attitudes regarding use of stimulant medication, and their influence on treatment decisions. METHODS: Using in-depth qualitative interviews, 12 adolescents with ADHD aged 12 – 15 years, and their parents described their experiences of ADHD and its treatment. Twenty four interviews, 12 with adolescents and 12 with their parents elicited detailed descriptions of beliefs about ADHD, attitudes about stimulant use and the circumstances surrounding treatment decisions. Verbatim transcripts were iteratively analyzed by a team of researchers following an interpretive interactionist framework. RESULTS: Young people offered three themes describing ADHD: 1) personality trait, 2) physical condition or disorder, and 3) minor issue or concern. Regarding medication use, youth described 1) benefits, 2) changes in sense of self, 3) adverse effects, and 4) desire to discontinue use. Parents’ beliefs were more homogeneous than youth beliefs, describing ADHD as a disorder requiring treatment. Most parents noted benefits from stimulant use. Themes were 1) medication as a last resort, 2) allowing the child to reach his or her potential; and 3) concerns about adverse and long-term effects. Families described how responsibility for treatment decisions is transferred from parent to adolescent over time. CONCLUSIONS: Young adolescents can have different beliefs about ADHD and attitudes about medication use from their parents. These beliefs and attitudes influence treatment adherence. Incorporating input from young adolescents when making clinical decisions could potentially improve continuity of treatment for youth with ADHD

Defining and targeting tumor-associated macrophages in malignant mesothelioma

Defining the ontogeny of tumor-associated macrophages (TAM) is important to develop therapeutic targets for mesothelioma. We identified two distinct macrophage populations in mouse peritoneal and pleural cavities, the monocyte-derived, small peritoneal/pleural macrophages (SPM), and the tissue-resident large peritoneal/pleural macrophages (LPM). SPM rapidly increased in tumor microenvironment after tumor challenge and contributed to the vast majority of M2-like TAM. The selective depletion of M2-like TAM by conditional deletion of the Dicer1 gene in myeloid cells (D$^{-/-}$) promoted tumor rejection. Sorted SPM M2-like TAM initiated tumorigenesis in vivo and in vitro, confirming their capacity to support tumor development. The transcriptomic and single-cell RNA sequencing analysis demonstrated that both SPM and LPM contributed to the tumor microenvironment by promoting the IL-2-STAT5 signaling pathway, inflammation, and epithelial-mesenchymal transition. However, while SPM preferentially activated the KRAS and TNF-α/NFkB signaling pathways, LPM activated the IFN-γ response. The importance of LPM in the immune response was confirmed by depleting LPM with intrapleural clodronate liposomes, which abrogated the antitumoral memory immunity. SPM gene signature could be identified in pleural effusion and tumor from patients with untreated mesothelioma. Five genes, TREM2, STAB1, LAIR1, GPNMB, and MARCO, could potentially be specific therapeutic targets. Accordingly, Trem2 gene deletion led to reduced SPM M2-like TAM with compensatory increase in LPM and slower tumor growth. Overall, these experiments demonstrate that SPM M2-like TAM play a key role in mesothelioma development, while LPM more specifically contribute to the immune response. Therefore, selective targeting of monocyte-derived TAM may enhance antitumor immunity through compensatory expansion of tissue-resident TAM

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Assessing children’s perceptual sensitivity to social information

Recent theories of social-cognitive development have generally focused on the development of theory of mind betweeninfancy and preschool. However, social understanding involves more than developing an inferential understanding of mindand continues beyond the early childhood years. We present preliminary findings from a study that evaluated childrensperceptual sensitivity to subtle kinematic cues that distinguish between intentions in others behaviour, based on Pesquita etal. (2016). On each trial, children observed videos of an actor reaching to touch one of two buttons. On half the trials theactor chose which button to touch and on the other half they were directed. A paired-samples t-test showed that participantswere reliably faster at correctly predicting the actors movement in the chosen condition than the directed condition [t(39)= 6.23, p ¡ .01, Cohens d = 0.99)]. We argue that social understanding comes in various forms and at different levels ofawareness

The influence of the self-perspective in infant theory of mind

We examine whether development of self-awareness influences infants’ ability to track and use others’ perspectives to make belief-based action predictions. Based on the altercentric hypothesis (Southgate, 2020), we expect that infants who do not yet have a self-perspective to make more accurate predictions of an agent’s actions on a non-verbal mentalizing task (NVMT) compared to infants who may encode the other’s and their own conflicting perspective. To test this, we presented 18-month-olds, half of whom passed the mirror self-recognition (MSR) task, with a NVMT and used anticipatory looking as a measure of action-based attribution. Contrary to our hypothesis, preliminary findings with 32 infants using the differential looking score, suggest that those who pass the MSR task are more accurate in their anticipatory looking compared to infants who do not pass the MSR task. All other preregistered analyses will be conducted once data collection is complete in June 2021

Altercententric interference vs. bias in 7.5 month-old infants: a pupillometry study

In a preregistered pupillometry study we tested whether a perspective cue can both increase and decrease 7.5-month-olds' surprise. In the congruent condition infants saw an agent watching a ball roll behind an occluder. After the agent left, infants saw the ball rolling outside the stage (an informational asymmetry). In the baseline the agent watched the final event as well. At outcome, the occluder was lowered to reveal empty space: congruent with reality, as the ball is out. In the incongruent condition the outcome is identical, but the ball should have been there. Informational asymmetry was manipulated again. We found overall larger pupil dilation in the incongruent condition, indicating infants’ remembering the ball’s existence. As hypothesised, we could increase their surprise in the congruent condition by having the agent last see the ball inside, but found mixed results when trying to use the perspective cue to also decrease infants’ surprise

Conflict between self and other in the development of perspective tracking

We examine whether infants and young children experience “conflict” between their own perspective and that of another in a false belief scenario. Based on the altercentric hypothesis, we propose that young infants can track the perspective of others because they lack a competing self-perspective. With the emergence of self-awareness, children may then be able to generate a representation of their own perspective and only then does this become a competitor to the perspective cued by others. To test this, we presented 18- and 42-month-olds with a perspective-conflict scenario and used pupil diameter as an index of conflicting processing. Half of the 18-month-olds passed the mirror self-recognition (MSR) task. Functional t-tests showed that MSR recognizers had greater dilation during the anticipatory phase compared to non-recognizers. Data collection with 42-month-olds is ongoing; preliminary results from pilot data suggests that the pupil trace of the 42-month-olds is similar to the MSR recognizers

Exploring stimulant treatment in ADHD: narratives of young adolescents and their parents

Abstract Background Young adolescents’ and their parents’ experiences with Attention-Deficit/Hyperactivity Disorder (ADHD) and its treatment were explored to investigate beliefs and attitudes regarding use of stimulant medication, and their influence on treatment decisions. Methods Using in-depth qualitative interviews, 12 adolescents with ADHD aged 12 – 15 years, and their parents described their experiences of ADHD and its treatment. Twenty four interviews, 12 with adolescents and 12 with their parents elicited detailed descriptions of beliefs about ADHD, attitudes about stimulant use and the circumstances surrounding treatment decisions. Verbatim transcripts were iteratively analyzed by a team of researchers following an interpretive interactionist framework. Results Young people offered three themes describing ADHD: 1) personality trait, 2) physical condition or disorder, and 3) minor issue or concern. Regarding medication use, youth described 1) benefits, 2) changes in sense of self, 3) adverse effects, and 4) desire to discontinue use. Parents’ beliefs were more homogeneous than youth beliefs, describing ADHD as a disorder requiring treatment. Most parents noted benefits from stimulant use. Themes were 1) medication as a last resort, 2) allowing the child to reach his or her potential; and 3) concerns about adverse and long-term effects. Families described how responsibility for treatment decisions is transferred from parent to adolescent over time. Conclusions Young adolescents can have different beliefs about ADHD and attitudes about medication use from their parents. These beliefs and attitudes influence treatment adherence. Incorporating input from young adolescents when making clinical decisions could potentially improve continuity of treatment for youth with ADHD