Psychosocial Outcomes in Autistic Children Before and During the COVID-19 Pandemic

Studies on the impact of the COVID-19 pandemic on autistic children’s psychosocial outcomes have shown mixed results. In the current study we aimed to gain a better insight into the effect of the COVID-19 pandemic by comparing psychosocial outcomes collected pre-pandemic with data collected during the pandemic. We used the Strengths and Difficulties Questionnaire (SDQ) to examine change over time in psychosocial outcomes of autistic children from pre-pandemic (T0) to lockdown I (T1) and lockdown II (T2) in the Netherlands. We expected a deterioration in psychosocial outcomes. There were 224 participants in T0 and T1, of which 141 also participated in T2. The results showed a surprising improvement in psychosocial outcomes from T0 to T1. Special education and female gender were associated with increased difficulties over time, while higher age was associated with decreased difficulties. At the subdomain level we found that emotional problems remained stable, while hyperactivity, conduct problems, and peer problems decreased, and prosocial behavior increased. Attending special education predicted increased peer problems over time, while higher age predicted both decreased conduct problems and increased prosocial behavior over time. The COVID-19 pandemic may have temporarily improved the fit between the psychosocial needs and the environment for children with autism in the Netherlands.</p

No preconscious attentional bias towards itch in healthy individuals

Rapidly attending towards potentially harmful stimuli to prevent possible damage to the body is a critical component of adaptive behavior. Research suggests that individuals display an attentional bias, i.e., preferential allocation of attention, for consciously perceived bodily sensations that signal potential threat, like itch or pain. Evidence is not yet clear whether an attentional bias also exists for stimuli that have been presented for such a short duration that they do not enter the stream of consciousness. This study investigated whether a preconscious attentional bias towards itch-related pictures exists in 127 healthy participants and whether this can be influenced by priming with mild itch-related stimuli compared to control stimuli. Mild itch was induced with von Frey monofilaments and scratching sounds, while control stimuli where of matched modalities but neutral. Attentional bias was measured with a subliminal pictorial dot-probe task. Moreover, we investigated how attentional inhibition of irrelevant information and the ability to switch between different tasks, i.e., cognitive flexibility, contribute to the emergence of an attentional bias. Attentional inhibition was measured with a Flanker paradigm and cognitive flexibility was measured with a cued-switching paradigm. Contrary to our expectations, results showed that participants attention was not biased towards the itch-related pictures, in facts, attention was significantly drawn towards the neutral pictures. In addition, no effect of the itch-related priming was observed. Finally, this effect was not influenced by participants' attentional inhibition and cognitive flexibility. Therefore, we have no evidence for a preconscious attentional bias towards itch stimuli. The role of preconscious attentional bias in patients with chronic itch should be investigated in future studies

Positive parenting in foster care: Testing the effectiveness of a video-feedback intervention program on foster parents’ behavior and attitudes

The current randomized controlled trial examined the effectiveness of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline in Foster Care (VIPP-FC) on parenting behavior and attitudes in foster parents (N = 60, 31–61 years, 83% female). The intervention group (n = 30) received VIPP-FC, consisting of six sessions. During the first four sessions, a specific theme from Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD; e.g., attachment vs. exploration behavior), and an additional foster care theme (e.g., subtle or missing attachment signals) are discussed. Each theme is discussed during the consecutive sessions and the last two sessions are booster sessions during which all themes are discussed. The control group (n = 30) received a dummy intervention consisting of six telephone calls about general child developmental topics. The Ainsworth Scales for sensitivity and non-interference, the Erickson scale for supportive presence, and the Questionnaire Attitudes towards Parenting were used to measure parental sensitivity, sensitive discipline, and attitudes towards parenting, respectively. The intervention and control group did not differ on demographic characteristics or outcome variables at pretest. Multilevel analyses based on the intent-to-treat principle yielded no evidence that VIPP-FC was more effective in improving foster parents’ sensitive parenting behavior or eliciting more positive attitudes compared to the control condition. We suggest that the outcomes in this study may be explained by a possible selection bias, which may have resulted in a ceiling effect. Future research might include foster families that experience more severe challenges (i.e., elevated levels of child behavior problems) or indicate a need for help and support

Visualization of Genomic Changes by Segmented Smoothing Using an L0 Penalty

Copy number variations (CNV) and allelic imbalance in tumor tissue can show strong segmentation. Their graphical presentation can be enhanced by appropriate smoothing. Existing signal and scatterplot smoothers do not respect segmentation well. We present novel algorithms that use a penalty on the norm of differences of neighboring values. Visualization is our main goal, but we compare classification performance to that of VEGA

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Funder: Ludwig Center at HarvardFunder: National Cancer Institute: K22CA193848Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266Abstract: Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer