Search

Purpose of review In this review, we explore the chromatin-related consequences of laminopathy-linked mutations through the lens of mechanotransduction. Recent findings Multiple studies have highlighted the role of the nuclear lamina in maintaining the integrity of the nucleus. The lamina also has a critical role in 3D genome organization. Mutations in lamina proteins associated with various laminopathies result in the loss of organization of DNA at the nuclear periphery. However, it remains unclear if or how these two aspects of lamin function are connected. Recent data suggests that unlinking the cytoskeleton from the nuclear lamina may be beneficial to slow progress of deleterious phenotypes observed in laminopathies. Summary In this review, we highlight emerging data that suggest interlinked chromatin- and mechanical biology-related pathways are interconnected in the pathogenesis of laminopathies.

PURPOSE: We aimed to increase Serious Illness Conversations (SIC) from a baseline of, at or near, zero to 25% of eligible patients by December 31, 2020. METHODS: We assembled an interdisciplinary team inclusive of a family partner and used the Model for Improvement as our quality improvement framework. The team developed a SMART Aim, key driver diagram, and SIC workflow. Standardized screening for SIC eligibility was implemented using the 2-year surprise question. Team members were trained in SIC communication skills by a trained facilitator and received ongoing coaching in quality improvement. We performed Plan-Do-Study-Act cycles and used audit-feedback data in weekly team meetings to inform iterative Plan-Do-Study-Act cycles. The primary outcome was the percent of eligible patients with documented SIC. RESULTS: Over 18 months, three clinics identified 63 eligible patients; of these, 32 (51%) were diagnosed with head and neck cancer and 31 (49%) with sarcoma. The SIC increased from a baseline near zero to 43 of 63 (70%) patients demonstrating three shifts in the median (95% CI). Conversations were interdisciplinary with 25 (57%) by oncology MD, six (14%) by advanced practice registered nurse, and 13 (30%) by specialty palliative care. We targeted four key drivers: (1) standardized work, (2) engaged interdisciplinary team, (3) engaged patients and families, and (4) system-level support. CONCLUSION: Our approach was successful in its documentation of end points and required resource investment (training and time) to embed into team workflows. Future work will evaluate scaling the approach across multiple clinics, the patient experience, and outcomes of care associated with oncology clinician–led SIC.

Introduction Early access to specialty palliative care is associated with better quality of life, less intensive end-of-life treatment and improved outcomes for patients with advanced cancer. However, significant variation exists in implementation and integration of palliative care. This study compares the organizational, sociocultural, and clinical factors that support or hinder palliative care integration across three U.S. cancer centers using an in-depth mixed methods case study design and proposes a middle range theory to further characterize specialty palliative care integration. Methods Mixed methods data collection included document review, semi-structured interviews, direct clinical observation, and context data related to site characteristics and patient demographics. A mixed inductive and deductive approach and triangulation was used to analyze and compare sites’ palliative care delivery models, organizational structures, social norms, and clinician beliefs and practices. Results Sites included an urban center in the Midwest and two in the Southeast. Data included 62 clinician and 27 leader interviews, observations of 410 inpatient and outpatient encounters and seven non-encounter-based meetings, and multiple documents. Two sites had high levels of “favorable” organizational influences for specialty palliative care integration, including screening, policies, and other structures facilitating integration of specialty palliative care into advanced cancer care. The third site lacked formal organizational policies and structures for specialty palliative care, had a small specialty palliative care team, espoused an organizational identity linked to treatment innovation, and demonstrated strong social norms for oncologist primacy in decision making. This combination led to low levels of specialty palliative care integration and greater reliance on individual clinicians to initiate palliative care. Conclusion Integration of specialty palliative care services in advanced cancer care was associated with a complex interaction of organization-level factors, social norms, and individual clinician orientation. The resulting middle range theory suggests that formal structures and policies for specialty palliative care combined with supportive social norms are associated with greater palliative care integration in advanced cancer care, and less influence of individual clinician preferences or tendencies to continue treatment. These results suggest multi-faceted efforts at different levels, including social norms, may be needed to improve specialty palliative care integration for advanced cancer patients.

Intrinsic stressors associated with life-history stages may alter the responsiveness of the hypothalamic-pituitary-adrenal axis and responses to extrinsic stressors. We administered adrenocorticotropic hormone (ACTH) to 24 free-ranging adult female northern elephant seals (NES) at two life-history stages: early and late in their molting period and measured a suite of endocrine, immune and metabolite responses. Our objective was to evaluate the impact of extended, high-energy fasting on adrenal responsiveness. Animals were blood sampled every 30 min for 120 min post-ACTH injection, then blood sampled 24 hrs later. In response to ACTH injection, cortisol levels increased 8-10-fold and remained highly elevated compared to baseline at 24 hr. Aldosterone levels increased 6-9-fold before returning to baseline at 24 hr. The magnitude of cortisol and aldosterone release were strongly associated, and both were greater after extended fasting. We observed an inverse relationship between fat mass and the magnitude of cortisol and aldosterone responses, suggesting that body reserves influenced adrenal responsiveness. Sustained elevation in cortisol was associated with alterations in thyroid hormones; both tT3 and tT4 concentrations were suppressed at 24 hr, while rT3 increased. Immune cytokine IL-1β was also suppressed after 24 hrs. of cortisol elevation, and numerous acute and sustained impacts on substrate metabolism were evident. Our data suggest that female NES are more sensitive to stress after the molt fast and that acute stress events can have important impacts on metabolism and immune function. These findings highlight the importance of considering life-history context when assessing the impacts of anthropogenic stressors on wildlife.

Antimicrobial-resistant (AMR) infections continue to rise dramatically, and the lack of new approved antibiotics is not ameliorating this crisis. A promising route to reduce AMR is by targeting virulence.

Adverse events related to palbociclib treatment

Palbociclib treated 3D time course

Palbociclib's stromal impact and cancer outcomes

Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role. We carried out a bioassay in the high-fat diet (HFD)-fed C57BL/6J mice to provide insight into the mechanisms of obesity-related HCC by studying γ-OHPdG, a mutagenic DNA adduct derived from lipid peroxidation. In an 80-week bioassay, mice received a low-fat diet (LFD), high-fat diet (HFD), and HFD with 2% Theaphenon E (TE) (HFD+TE). HFD mice developed a 42% incidence of HCC and LFD mice a 16%. Remarkably, TE, a standardized green tea extract formulation, completely blocked HCC in HFD mice with a 0% incidence. γ-OHPdG measured in the hepatic DNA of mice fed HFD and HFD+TE showed its levels increased during the early stages of NAFLD in HFD mice and the increases were significantly suppressed by TE, correlating with the tumor data. Whole-exome sequencing showed an increased mutation load in the liver tumors of HFD mice with G>A and G>T as the predominant mutations, consistent with the report that γ-OHPdG induces G>A and G>T. Furthermore, the mutation loads were significantly reduced in HFD+TE mice, particularly G>T, the most common mutation in human HCC. These results demonstrate in a relevant model of obesity-induced HCC that γ-OHPdG formation during fatty liver disease may be an initiating event for accumulated mutations that leads to HCC and this process can be effectively inhibited by TE. Cancer Prev Res; 11(10); 665–76. ©2018 AACR.

S1,S2,S3,S4,S5,S6,S7, Supplemental table 1,supplemental table 2

Supplementary Table 1

Supplementary Methods: Supplementary Table 1 and 2

Palbociclib's transcriptomic effects on tumors

MUC16 and Tumor cell Death

Targeted monoclonal antibody therapy is a promising therapeutic strategy for cancer, and antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial mechanism underlying these approaches. The majority of patients have limited responses to monoclonal antibody therapy due to the development of resistance. Models of ADCC provide a system for uncovering immune-resistance mechanisms. We continuously exposed epidermal growth factor receptor (EGFR+) A431 cells to KIR-deficient NK92-CD16V effector cells and the anti-EGFR cetuximab. Persistent ADCC exposure yielded ADCC-resistant cells (ADCCR1) that, compared with control ADCC-sensitive cells (ADCCS1), exhibited reduced EGFR expression, overexpression of histone- and interferon-related genes, and a failure to activate NK cells, without evidence of epithelial-to-mesenchymal transition. These properties gradually reversed following withdrawal of ADCC selection pressure. The development of resistance was associated with lower expression of multiple cell-surface molecules that contribute to cell–cell interactions and immune synapse formation. Classic immune checkpoints did not modulate ADCC in this unique model system of immune resistance. We showed that the induction of ADCC resistance involves genetic and epigenetic changes that lead to a general loss of target cell adhesion properties that are required for the establishment of an immune synapse, killer cell activation, and target cell cytotoxicity.

Canonical effects of CDK4/6 inhibition

Palbociclib in the MIND Model

Legends for Supplemental Figures 1-7 in Supplementary Data file

Supplementary tables and figures for study

A) Representative images of hematoxylin and eosin (H&E) staining of MCFDCIS, MCFDCIS-Î"4 and mixed (4:1 respectively) tumors that were injected in the mammary fat pad of SCID/Beige mice after two or five weeks. MCFDCIS-Î"4 tumors were not collected at two weeks due to small tumor size. Scale bar=50μm. B) Growth of subcutaneous tumors of DCIS or DCIS-Î"4-hy in athymic nude mice. n=5. **p

A list of differentially expressed genes in tumors and cells.

A) Principal component analyses of RNA-Seq from MCFDCIS and MCF10A cell lines and the AIB1Î"4 corresponding clones. B) Relapse free survival and overall survival KM-plots in patients with ER-negative breast tumors separated by AIB1Î"4 top regulated genes in MCFDCIS cells. AIB1Î"4 signature gene list used to generate the KM-plots is in Supplementary table S3. C) Volcano plots illustrating differentially expressed genes (DEGs) regulated by AIB1Î"4 in MCF10A cell clones (|log2(FC)|>1.5 and -log(adj p-val)>1.3). Full list of DEGs in Supplementary table S1. D) Significantly enriched hallmark pathways from gene set enrichment analyses (GSEA) associated with AIB1Î"4 expression in MCF10A cells. Full list of enriched pathways in Supplementary table S2. E) Top canonical pathways altered in MCF10A-Î"4 compared to control MCF10A cells identified by Ingenuity Pathway Analysis (IPA). |z-score|>1, p-val 1.5 and -log(adj p-val)>1.3). Full list of DEGs in Supplementary table S1.

A) FDR-corrected shared and unique ChIP peaks of AIB1 and AIB1Î"4 in MCF10A parental cell line (10A) versus AIB1Î"4-expressing isogenic line (10A-Î"4). Shared peaks have at least 1bp overlap. B) AIB1 ChIP peaks in MCF7 cells treated for 3 hours with estradiol (E2) or vehicle (V) overlapped with MCF10A and MCFDCIS (parental and AIB1Î"4 derivative lines). MCF7 data set obtained from Zwart et al(32). C) Motifs within 200 bp of the peak summit for significant ChIP-Seq peaks were analyzed for motif enrichment using HOMER. In red are the motifs unique to AIB1Î"4 in MCF10A cells. D) FDR-corrected histone modification peaks in DCIS and DCIS-Î"4 overlapping with enhancer sites from human mammary epithelial cells (hMEC enh.) (42). E) The distribution of AIB1, H3K27ac or H3K4me1 ChIP peaks 500 kb up- and downstream of gene transcription start site (TSS). Genomic distance was divided into 5kb bins.

A) Quantification of the number of Zebrafish embryos with DCIS or DCIS-Î"4-hy cells that have extravasated out of the blood vessels and into the neighboring tissue. p=0.57. B) Quantification of the number of Zebrafish embryos with MCF10A, MCF10A-Î"4 or mixed cells that have extravasated out of the blood vessels and into the neighboring tissue. In the mixed cell population, only MCF10A parental line was fluorescently labeled and scored for extravasation. MCF10A and MCF10A-Î"4 are mixed at a 4:1 ratio. C) Invasion assay of an endothelial monolayer (HUVEC) using ECIS. MCFDCIS cells were treated with conditioned media (CM) from MCFDCIS-Î"4 cells for 4 hours before added to the endothelial monolayer, and vice versa. No cells added to the endothelial monolayer as a negative control. D) A schematic showing a three-chambered co-culture system. Top chamber has electrodes underneath a porous membrane to detect migrating cells. Middle chamber is only permeable to factors but not cells. Bottom chamber harbors cells that can crosstalk with migrating cells through secreted factors. E) Real-time migration rate of MCFDCIS and MCFDCIS-Î"4 in co-culture chambers. F) MCFDCIS and MCFDCIS-Î"4 cells were aggregated separately then embedded in 80% col I and 20% Matrigel together to monitor their crosstalk as separate spheres. Scale bar = 50μm.

A list of AIB1Î"4 signature genes that were used to generate KM-plots in Figure S5.

A) Sequence alignment of PCR amplicons of genomic DNA spanning exon 4 of AIB1 (UCSC genome browser). Black filled boxes are the sequences that align to the genome and dotted lines represent the missing/deleted sequences. AIB1 in the DCIS-Î"4 cell line is missing part of intron 3 and exon 4. Two deleted regions around exon 4 of AIB1 were identified in the 10A-Î"4 cell line; both are missing exon 4 acceptor site. B) Sanger sequencing of PCR amplicons spanning exons 2, 3, 4, 5 splice junctions. C) AIB1 mRNA between exon 2 and exon 5 in the MCFDCIS-Î"4 cell clones and the parental MCFDCIS cells. D) Western blot shows AIB1 isoforms' protein expression in MCFDCIS-Î"4 cell clones and the parental MCFDCIS cells. E) Schematic of the migration, trans-endothelial invasion and proliferation assays using real time electric cell impedance sensing (ECIS) to detect migrating cells, invasion across an endothelial monolayer or proliferation rate. F) Invasion of DCIS-Î"4-hy across an endothelial monolayer using ECIS compared to parental control DCIS cells. G) Cell proliferation of MCFDCIS (DCIS), DCIS-Î"4 and DCIS-Î"4-hy measured by electric cell impedance sensing (ECIS). A single well coated with electrodes was used to measure real time change in cell impedance as they proliferate over 80 hours (See diagram in S1E). H) Cell proliferation of MCFDCIS and MCF10A parental lines and their AIB1Î"4 expressing counterpart. ***p

A list of enriched pathways using Gene Set Enrichment Analysis (GSEA).

AIB1Δ4 is an N-terminally truncated isoform of the oncogene amplified in breast cancer 1 (AIB1) with increased expression in high-grade human ductal carcinoma in situ (DCIS). However, the role of AIB1Δ4 in DCIS malignant progression has not been defined. Here we CRISPR-engineered RNA splice junctions to produce normal and early-stage DCIS breast epithelial cells that expressed only AIB1Δ4. These cells showed enhanced motility and invasion in 3D cell culture. In zebrafish, AIB1Δ4-expressing cells enabled invasion of parental cells when present in a mixed population. In mouse xenografts, a subpopulation of AIB1Δ4 cells mixed with parental cells enhanced tumor growth, recurrence, and lung metastasis. AIB1Δ4 chromatin immunoprecipitation sequencing revealed enhanced binding to regions including peroxisome proliferator-activated receptor (PPAR) and glucocorticoid receptor (GR) genomic recognition sites. H3K27ac and H3K4me1 genomic engagement patterns revealed selective activation of breast cancer-specific enhancer sites by AIB1Δ4. AIB1Δ4 cells displayed upregulated inflammatory response genes and downregulated PPAR signaling gene expression patterns. In the presence of AIB1Δ4 enabler cells, parental cells increased NF-κB and WNT signaling. Cellular cross-talk was inhibited by the PPARγ agonist efatutazone but was enhanced by treatment with the GR agonist dexamethasone. In conclusion, expression of the AIB1Δ4-selective cistrome in a small subpopulation of cells triggers an “enabler” phenotype hallmarked by an invasive transcriptional program and collective malignant progression in a heterogeneous tumor population.Significance:A minor subset of early-stage breast cancer cells expressing AIB1Δ4 enables bulk tumor cells to become invasive, suggesting that selective eradication of this population could impair breast cancer metastasis.

Supplementary Methods

Realist reviews have shown the effectiveness of participatory action research but the realist approach has not been used in combination with a participatory approach in qualitative data analysis.To study the links between preexisting conditions in neighborhoods and the kind of actions taken at the community level during the coronavirus disease 2019 pandemic in Toronto, a community-university research partnership used a critical realist approach to analyze qualitative interviews with grassroots leaders. This article describes the procedures developed to enable participation of the full community- academic team in the analysis.One analyst coded paragraphs in all 46 interviews for preexisting conditions (contexts), actions taken (intervention components), the often implicit factors that underpinned the actions (mechanisms), and observed results (outcomes) as stated by the interviewees. Each interview was summarized in terms of the contexts (C), actions (I), mechanisms (M) and outcomes (O) identified and one to seven midrange CIMO hypotheses were developed for each interview. A second level of analysis involved sense-making workshops with the community partner and a cross-section of interviewees using the CIMO statements.This article describes the realist approach to analysis and the changes that were made to enable a mixed team of community leaders and academics to generate overall statements of impact. This is a novel approach to qualitative data analysis, with a range of implications for the use of this technique in participatory research.

Supplementary Material 2

Supplementary Material 3

Background Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease. Results To address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state. Conclusions Altogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.

In this commentary, we describe initial learnings from a community-based research project that explored how the relational space between residents and formal institutions in six marginalised communities in Toronto, Ontario, Canada impacted grassroots responses to the health and psycho-social stresses that were created and amplified by the coronavirus disease 2019 (COVID-19) pandemic. Our research found that grassroots community leaders stepped up to fill the gaps left by Toronto’s formal public health and emergency management systems and were essential for mitigating the psycho-social and socioeconomic impacts of the pandemic that exacerbated pre-existing inequities and systemic failures. We suggest that building community resilience in marginalised communities in Toronto can embody health promotion in action where community members, organisational, institutional and government players create the social infrastructure necessary to build on local assets and work together to promote health by strengthening community action, advocating for healthy public policy and creating supportive environments.

It has been shown that the Metropolis algorithm can be implemented on quantum computers in a way that avoids the sign problem. However, flat histogram techniques are often preferred as they don't suffer from the same limitations that afflict Metropolis for problems of real-world interest and provide a host of other benefits. In particular, the Wang-Landau method is known for its efficiency and accuracy. In this work we design, implement, and validate a quantum algorithm for Wang-Landau sampling, greatly expanding the range of quantum many body problems solvable by Monte Carlo simulation.

Gender inequality perpetuates women’s economic insecurity and a culture of violence. Parental distress caused by economic pressure may increase violence against children. High levels of gender inequality and interpersonal violence may contribute to higher levels of physical abuse. Using an ecological perspective, this study examines the association of country-level gender inequality and household-level parental physical abuse, and the moderating role of child gender in this association in low- and middle-income countries. We used data on over 420,000 households from the UNICEF Multiple Indicator Cluster Surveys and country-level indicators from the United Nations Development Program Human Development data. We employed multilevel logistic regression to examine the association between gender inequality with the log-odds of physical abuse after accounting for country- and individual-level covariates. In order to more fully explore our results, we calculated predicted probabilities of abuse for several scenarios. The results indicated that higher levels of gender inequality were associated with higher probabilities of physical abuse. This association was stronger for female children than for male children. The probabilities of abuse by child gender were indistinguishable, although rates of physical abuse converged as gender inequality increased, at a statistically marginal level. These findings indicate that macro-level interventions that reduce gender inequality are necessary to prevent and reduce child physical abuse.

The state-of-the-art in machine learning has been achieved primarily by deep learning artificial neural networks. These networks are powerful but biologically implausible and energy intensive. In parallel, a new paradigm of neural network is being researched that can alleviate some of the computational and energy issues. These networks, spiking neural networks (SNNs), have transformative potential if the community is able to bridge the gap between deep learning and SNNs. However, SNNs are notoriously difficult to train and lack precision in their communication. In an effort to overcome these limitations and retain the benefits of the learning process in deep learning, we investigate novel ways to translate between them. We construct several network designs with varying degrees of biological plausibility. We then test our designs on an image classification task and demonstrate our designs allow for a customized tradeoff between biological plausibility, power efficiency, inference time, and accuracy., ICONS: International Conference on Neuromorphic Systems, July 27-29, 2022, Knoxville TN USA

In this article, we take a mathematical approach to the study of population-level disease spread, performing a quantitative and qualitative investigation of an SISκ model which is a susceptible-infectious-susceptible ( SIS ) model with exposure to an external disease reservoir. The external reservoir is non-dynamic, and exposure from the external reservoir is assumed to be proportional to the size of the susceptible population. The full stochastic system is modelled using a master equation formalism. A constant population size assumption allows us to solve for the stationary probability distribution, which is then used to investigate the predicted disease prevalence under a variety of conditions. By using this approach, we quantify outbreak vulnerability by performing the sensitivity analysis of disease prevalence to changing population characteristics. In addition, the shape of the probability density function is used to understand where, in parameter space, there is a transition from disease free, to disease present, and to a disease endemic system state. Finally, we use Kullback–Leibler divergence to compare our semi-analytical results for the SISκ model with more complex susceptible-infectious-recovered ( SIR ) and susceptible-exposed-infectious-recovered ( SEIR ) models.

The current study applied a family systems approach to examine dyadic parental risk factors linked with mother–father co-involved physical abuse, neglect, sexual abuse, and emotional abuse. Parental substance use, mental health problems, disability and medical conditions, inadequate housing, economic insecurity, intimate partner violence, and prior maltreatment history were investigated as key risk factors at the dyadic parental level. Logistic regression analysis was conducted using national child welfare administrative data from the National Child Abuse and Neglect Data System. The results showed differential associations between risk factors and four child maltreatment types: physical abuse, neglect, emotional abuse, and sexual abuse. Intimate partner violence was associated with higher odds of mother–father co-involved neglect and emotional abuse. Parental substance use, inadequate housing, and prior maltreatment history were all associated with higher odds of mother–father co-involved neglect, but lower odds of physical abuse. Parental disability and medical conditions were associated with higher odds of mother-father co-involved sexual abuse, whereas parental substance use was associated with lower odds of sexual abuse. Implications include more nuanced ways of addressing multiple risk factors within the family to prevent future occurrences of child maltreatment involving both mothers and fathers.

Most government emergency/pandemic response plans feature top-down decision making and communication strategies and a focus on 'hard' (physical) infrastructure. There is nothing about the importance of the ideas and communications originating from communities, the social infrastructure that supports their impact locally and their contribution to the central administration. In this study, we found that the 'soft' (social) infrastructure within communities and between communities and formal institutions is key to an inclusive and more equitable response to large-scale crises like the COVID-19 pandemic. Grassroots leaders in six Toronto neighbourhoods were interviewed between the first and second waves of the COVID-19 pandemic in Toronto about what helped or hindered community action. Three themes emerged: (1) Grassroots leaders and community organizations were able to act as key connection points in a two-way flow of information and resources with residents and service providers; (2) Grassroots leaders and groups were challenged to engage in this work in a sustained capacity without adequate resourcing; and (3) there was a disconnect between community-centred grassroots approaches and the City's emergency response. We conclude that there needs to be pre-disaster investment in community level planning and preparation that fosters two-way connections between all municipal emergency/disaster and pandemic preparedness plans and community-centred organizations and grassroots leaders working in marginalized communities.

Background and Objective: Sixty countries worldwide have banned the use of physical punishment, yet little is known about the association of physical and nonphysical forms of child discipline with child development in a global context. The objective of this study is to examine whether physical punishment and nonphysical discipline are associated with child socioemotional functioning in a global sample of families from 62 countries and whether country-level normativeness of physical punishment and nonphysical discipline moderated those associations. Methods: Data for this study are from 215,885 families in the fourth and fifth rounds of the United Nations Children’s Fund Multiple Indicator Cluster Surveys. Bayesian multilevel logistic models were used to analyze the associations of physical punishment and nonphysical discipline (i.e., taking away privileges and verbal reasoning) with three different outcomes representing children’s socioemotional functioning: getting along well with other children, aggression, and becoming distracted. Results: The use of physical punishment was not associated with getting along with other children, was associated with increased aggression, and was associated with increases in distraction. Taking away privileges was associated with lower levels of getting along with other children, higher levels of aggression, and higher levels of becoming distracted. Verbal reasoning (i.e., explaining why a behavior was wrong) was associated with higher levels of getting along with other children, higher levels of aggression, and higher levels of becoming distracted. Country-level normativeness moderated some of these associations but in general the direction of effects was consistent. Conclusions: Results suggest that eliminating physical punishment would benefit children across the globe and align with the United Nations Convention on the Rights of the Child, which calls for all children to be free from physical violence. More attention needs to be focused on the associations of nonphysical forms of discipline with child functioning across the globe.

The Locally Competitive Algorithm (LCA) uses local competition between non-spiking leaky integrator neurons to infer sparse representations, allowing for potentially real-time execution on massively parallel neuromorphic architectures such as Intel’s Loihi processor. Here, we focus on the problem of inferring sparse representations from streaming video using dictionaries of spatiotemporal features optimized in an unsupervised manner for sparse reconstruction. Non-spiking LCA has previously been used to achieve unsupervised learning of spatiotemporal dictionaries composed of convolutional kernels from raw, unlabeled video. We demonstrate how unsupervised dictionary learning with spiking LCA (S-LCA) can be efficiently implemented using accumulator neurons, which combine a conventional leaky-integrate-and-fire (LIF) spike generator with an additional state variable that is used to minimize the difference between the integrated input and the spiking output. We demonstrate dictionary learning across a wide range of dynamical regimes, from graded to intermittent spiking, for inferring sparse representations of both static images drawn from the CIFAR database as well as video frames captured from a DVS camera. On a classification task that requires identification of the suite from a deck of cards being rapidly flipped through as viewed by a DVS camera, we find essentially no degradation in performance as the LCA model used to infer sparse spatiotemporal representations migrates from graded to spiking. We conclude that accumulator neurons are likely to provide a powerful enabling component of future neuromorphic hardware for implementing online unsupervised learning of spatiotemporal dictionaries optimized for sparse reconstruction of streaming video from event based DVS cameras., ICONS: International Conference on Neuromorphic Systems, July 27-29, 2022, Knoxville, TN, USA