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Autism ◽  
2022 ◽  
pp. 136236132110666
Author(s):  
Karen Bearss ◽  
Daina Tagavi ◽  
Aaron R Lyon ◽  
Jill Locke

Teachers endorse disruptive behavior as a considerable concern for autistic students, which is compounded by the lack of adequate resources for behavioral intervention planning in the classroom. The RUBI program is an evidence-based, low-intensity manualized intervention, initially developed for parents of autistic children ages 3–14 and co-occurring disruptive behavior. Utilizing the Discover, Design/Build, Test (DDBT) framework, which combines user-centered design and implementation science, RUBI intervention content was collaboratively and iteratively redesigned with elementary school stakeholders (40 school staff from 28 schools) to ensure the feasibility, acceptability, and appropriateness of the redesigned intervention, RUBI in Educational Settings (RUBIES). Iterative quantitative and qualitative methods were conducted with stakeholders to identify targets for RUBI redesign. Conventional content analysis was used to code qualitative data and identify usability issues. Recommendations were provided for modifications to RUBI sessions to address the needs of the school context and end-users to develop RUBIES. Feasibility scores improved following the redesign. The use of the DDBT framework to redesign the RUBI intervention may promote greater usefulness and usability in school contexts. Lay abstract Teachers often report concerns about behavior challenges in their students with autism spectrum disorder (ASD) in the school setting. Furthermore, teachers often report that they do not have adequate training in how to manage these challenging behaviors effectively. The RUBI program is an intervention initially developed for parents of children with ASD and co-occurring challenging behavior in clinic settings. The present project used school staff input to systematically redesign RUBI to be used with educators in schools. School staff gave input at multiple stages of development to ensure the adapted intervention was appropriate to use in a school setting. Responses were coded and analyzed to identify strengths and weaknesses of the RUBI manual in schools and adaptations were made accordingly. Scores of how appropriate, possible, likable, and usable RUBI would be in schools rose after the intervention was redesigned. The redesigned RUBIES manual may give school staff the tools they need to manage disruptive behaviors. In addition, collaborating with providers over multiple stages to redesign established interventions for new contexts may be a promising way to help bring research tools to practice in the future.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Bassam Khaleel Al-Abbasi

Abstract Background Diphallus (duplication of phallus) is rarely encountered in surgical practice with only 100 cases reported in literature. Some cases may be isolated but mostly associated with other anomalies, without clear data about its etiology. Case presentation We reported a 1-day-old newborn baby who was presented with complete duplication of the phallus, one of them being hypospadic associated with a high type imperforate anus, omphalocele, congenital pouch colon, sacral meningocele, and other congenital anomalies not reported before in such combinations. Multiple stages surgical corrective procedures were performed over a period of 4 years with 4–6 months interval between each stage, starting with the management of omphalocele and colostomy, ended by excision of the abnormal phallus with abdominoplasty and closure of colostomy. The outcome was evaluated, and literatures were reviewed in relation to types, presentations, and options for surgical correction with optimal outcomes. Conclusion A combination of diphallia and other abnormalities in our patient are not reported previously in such manner and were very difficult to be corrected. Only expert pediatric surgeons should treat such conditions as every case is unique in nature. In all conditions, the abnormal phallus should be excised, and the final aim is to achieve a continent child with cosmetically acceptable genitalia.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ariel X.-A. Goh ◽  
Daniel Bennett ◽  
Stefan Bode ◽  
Trevor T.-J. Chong

AbstractHumans have a striking desire to actively seek new information, even when it is devoid of any instrumental utility. However, the mechanisms that drive individuals’ subjective preference for information remain unclear. Here, we used fMRI to examine the processing of subjective information value, by having participants decide how much effort they were willing to trade-off for non-instrumental information. We showed that choices were best described by a model that accounted for: (1) the variability in individuals’ estimates of uncertainty, (2) their desire to reduce that uncertainty, and (3) their subjective preference for positively valenced information. Model-based analyses revealed the anterior cingulate as a key node that encodes the subjective value of information across multiple stages of decision-making – including when information was prospectively valued, and when the outcome was definitively delivered. These findings emphasise the multidimensionality of information value, and reveal the neurocomputational mechanisms underlying the variability in individuals’ desire to physically pursue informative outcomes.


Cognition ◽  
2021 ◽  
Vol 217 ◽  
pp. 104892
Author(s):  
Alice Liefgreen ◽  
Sami R. Yousif ◽  
Frank C. Keil ◽  
David A. Lagnado

2021 ◽  
Author(s):  
Nafiseh Erfanian ◽  
A. Ali Heydari ◽  
Pablo Ianez ◽  
Afshin Derakhshani ◽  
Mohammad Ghasemigol ◽  
...  

Deep learning (DL) is a branch of machine learning (ML) capable of extracting high-level features from raw inputs in multiple stages. Compared to traditional ML, DL models have provided significant improvements across a range of domains and applications. Single-cell (SC) omics are often high-dimensional, sparse, and complex, making DL techniques ideal for analyzing and processing such data. We examine DL applications in a variety of single-cell omics (genomics, transcriptomics, proteomics, metabolomics and multi-omics integration) and address whether DL techniques will prove to be advantageous or if the SC omics domain poses unique challenges. Through a systematic literature review, we have found that DL has not yet revolutionized or addressed the most pressing challenges of the SC omics field. However, using DL models for single-cell omics has shown promising results (in many cases outperforming the previous state-of-the-art models) but lacking the needed biological interpretability in many cases. Although such developments have generally been gradual, recent advances reveal that DL methods can offer valuable resources in fast-tracking and advancing research in SC.


2021 ◽  
Author(s):  
◽  
Renée Anne Nankivell

<p>The demand for a new approach to safeguarding New Zealand’s endangered historic buildings was identified as a result of the recent increase in building code and strengthening requirements following the Christchurch earthquakes of 2010-2011. The Wellington City Council identified 266 heritage buildings in the city that must be either strengthened or demolished to address these increased requirements. This thesis explores this threat as an opportunity for researching how contemporary design interventions can be challenged to both strengthen and become active participants in the ongoing history of New Zealand’s potentially endangered historic buildings. This thesis challenges the current approach of completely ‘restoring’ 19th-20th century historic buildings in New Zealand, to develop techniques that structurally reinforce historic buildings while inviting the progressive weathering of a building to remain as a testament to its history. This thesis proposes a structural intervention that is responsive to the progressive history of historic buildings, simultaneously introducing a contemporary structural intervention that both participates in and compliments the progressive historic transformations of the vehicle. This thesis argues that current historic buildings in semi-decayed states in fact enable visitors to witness multiple stages in the life of a building, while fully restored buildings only enable visitors to witness the original form of the building. This thesis proposes a model for contemporary intervention within historic buildings that draws a design intervention from seismic strengthening.The notion of layering is explored as a design approach to incorporate the contemporary with the historic as an additional layer of exposed on-going history, thereby further exposing the layers of history evident within New Zealand’s historic buildings. This thesis combines layering theories of architects Louis Kahn and Carlo Scarpa with related theories of installation artist Mary Miss. The theoretical imperatives of Scarpa and Kahn are explored as a tool of engagement for the junction between the contemporary and historic building materials, and the work of Marry Miss is explored as a design approach for developing a contemporary intervention that references the layered historic building while inviting new means of occupancy between layers. The selected vehicle for the design research investigation is the Albemarle Hotel on Ghuznee Street in Wellington. The techniques proposed in this thesis to strengthen the Albemarle Hotel suggest an approach that might be applied to New Zealand’s wider body of historic buildings that constitute New Zealand’s heritage fabric, ultimately protecting them from demolition while preserving additional layers of their historic narratives. Over all the design research experiments suggest that contemporary interventions derived from structural strengthening may be a viable and cost-effective method of re-inhabiting New Zealand’s endangered heritage buildings, avoiding demolition and securing New Zealand’s heritage for future generations. Research Questions: This thesis challenges the current economically unsustainable approach of laterally reinforcing and completely ‘restoring’ 19th-20th century historic buildings in New Zealand. This thesis argues that current historic buildings in semi-decayed states in fact enable visitors to witness multiple stages in the on-going life of a building. Can the weathered state of New Zealand's heritage buildings be proactively retained and celebrated as witnesses to their history? Can new lateral reinforcing requirements be conceived as active participants in revealing the on-going history of New Zealand's historic buildings?</p>


2021 ◽  
Author(s):  
◽  
Renée Anne Nankivell

<p>The demand for a new approach to safeguarding New Zealand’s endangered historic buildings was identified as a result of the recent increase in building code and strengthening requirements following the Christchurch earthquakes of 2010-2011. The Wellington City Council identified 266 heritage buildings in the city that must be either strengthened or demolished to address these increased requirements. This thesis explores this threat as an opportunity for researching how contemporary design interventions can be challenged to both strengthen and become active participants in the ongoing history of New Zealand’s potentially endangered historic buildings. This thesis challenges the current approach of completely ‘restoring’ 19th-20th century historic buildings in New Zealand, to develop techniques that structurally reinforce historic buildings while inviting the progressive weathering of a building to remain as a testament to its history. This thesis proposes a structural intervention that is responsive to the progressive history of historic buildings, simultaneously introducing a contemporary structural intervention that both participates in and compliments the progressive historic transformations of the vehicle. This thesis argues that current historic buildings in semi-decayed states in fact enable visitors to witness multiple stages in the life of a building, while fully restored buildings only enable visitors to witness the original form of the building. This thesis proposes a model for contemporary intervention within historic buildings that draws a design intervention from seismic strengthening.The notion of layering is explored as a design approach to incorporate the contemporary with the historic as an additional layer of exposed on-going history, thereby further exposing the layers of history evident within New Zealand’s historic buildings. This thesis combines layering theories of architects Louis Kahn and Carlo Scarpa with related theories of installation artist Mary Miss. The theoretical imperatives of Scarpa and Kahn are explored as a tool of engagement for the junction between the contemporary and historic building materials, and the work of Marry Miss is explored as a design approach for developing a contemporary intervention that references the layered historic building while inviting new means of occupancy between layers. The selected vehicle for the design research investigation is the Albemarle Hotel on Ghuznee Street in Wellington. The techniques proposed in this thesis to strengthen the Albemarle Hotel suggest an approach that might be applied to New Zealand’s wider body of historic buildings that constitute New Zealand’s heritage fabric, ultimately protecting them from demolition while preserving additional layers of their historic narratives. Over all the design research experiments suggest that contemporary interventions derived from structural strengthening may be a viable and cost-effective method of re-inhabiting New Zealand’s endangered heritage buildings, avoiding demolition and securing New Zealand’s heritage for future generations. Research Questions: This thesis challenges the current economically unsustainable approach of laterally reinforcing and completely ‘restoring’ 19th-20th century historic buildings in New Zealand. This thesis argues that current historic buildings in semi-decayed states in fact enable visitors to witness multiple stages in the on-going life of a building. Can the weathered state of New Zealand's heritage buildings be proactively retained and celebrated as witnesses to their history? Can new lateral reinforcing requirements be conceived as active participants in revealing the on-going history of New Zealand's historic buildings?</p>


2021 ◽  
Vol 22 (22) ◽  
pp. 12199
Author(s):  
Ya-Ting Chuang ◽  
Wan-Chu Chuang ◽  
Chih-Chun Liu ◽  
Chia-Wei Liu ◽  
Yu-Wen Huang ◽  
...  

The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2068-2068
Author(s):  
Marina Feigenson ◽  
Remya Nathan ◽  
Joshua Lamora ◽  
Ffolliott Fisher ◽  
Claire C Tseng ◽  
...  

Abstract KER-050 is a modified ActRIIA ligand trap that is designed to inhibit the activity of the TGF-β ligands, including activin A, activin B, GDF8 and GDF11, that act through the SMAD2/3 signaling cascade. Notably, in a Phase 1 clinical study we observed that, in addition to increases in red blood cells and hemoglobin, treatment with KER-050 elicited a robust and sustained increase in platelets (PLTs) in healthy volunteers. While ActRII ligand traps have been shown to increase erythropoiesis in preclinical and clinical studies, their role in thrombopoiesis has not yet been well-elucidated. A variety of conditions exist where hematopoiesis is impaired and cytopenia persists, including comorbidities associated with aging, diseases causing ineffective hematopoiesis such as myelodysplastic syndrome (MDS) and myelofibrosis (MF), and acute bleeding. Thrombocytopenia can arise from primary or secondary causes due to multiple etiologies and treatments are limited, aiming at treating the root cause of disease or replacing PLTs through transfusion. Therefore, there is an unmet medical need for more targeted treatments to correct thrombocytopenia. Here, in a series of preclinical studies, we investigated the mechanism of action of KER-050 on thrombopoiesis and evaluated its ability to accelerate recovery from acute platelet depletion. First, we examined how RKER-050 (a research form of KER-050) affected thrombopoiesis under homeostatic conditions. We observed that a single intraperitoneal dose of RKER-050 (10 mg/kg) to 11-week-old mice resulted in a 2-fold increase in PLTs compared to vehicle-treated mice 12 hours after treatment. The timing of the effect is suggestive of a direct effect of RKER-050 on terminal platelet maturation. Additionally, there was a 35% increase in the number of bone marrow (BM) megakaryocyte (Mk) progenitors (Lin -; sca1 -; cKit -; CD41 + cells), demonstrating that RKER-050 affected earlier stages of the PLT formation process. We also evaluated the effect of RKER-050 on the polyploidization of Mks, a hallmark of Mk differentiation. At 24 hours after treatment with RKER-050, there was an increase in BM CD41 + cells with ploidy greater than 16N compared to vehicle-treated mice, demonstrating that RKER-050 treatment resulted in a greater number of Mk that are potentially primed for platelet production. Taken together, these data are consistent with RKER-050 affecting multiple stages of thrombopoiesis in a preclinical model. We next tested whether RKER-050 affects PLTs in a mouse model of immune thrombocytopenia (IT) where antibodies directed against mouse GPIbα result in acutely reduced PLT numbers. In this model, mice receiving anti-GPIbα had a 25% reduction in PLT number at 4 days post-dose compared to IgG control-treated mice. At this point, the anti-GPIba cohort was divided into receiving either a single dose of vehicle or RKER-050. On day 7 following anti-GPIbα treatment, PLT counts in vehicle-treated mice were 62% lower compared to IgG-control-treated mice. In contrast, the GPIbα-mediated effect on PLT count was stabilized in the anti-GPIbα + RKER-050 group, which had 55% more platelets compared to the anti-GPIba + vehicle group. These data suggest that RKER-050 promoted thrombopoiesis in mice even under conditions when the system is acutely challenged and potentially could promote faster recovery from thrombocytopenia. Additionally, we observed a 25% increase in the number of CD41 + cells in the BM of the RKER-050-treated group compared to the vehicle-treated group at day 10 after PLT depletion, suggesting that under acute thrombocytopenia, RKER-050 treatment promoted differentiation of Mks as a mechanism of the accelerated recovery in platelet-depleted mice. In summary, our preclinical data demonstrate a potentially novel effect of RKER-050 on thrombopoiesis. RKER-050 treatment resulted in a rapid increase in PLTs, consistent with an effect on terminal maturation. Treatment also increased the number of Mk progenitors and increased the number of polyploid Mks, demonstrating an effect on early stages of thrombopoiesis. These findings support that RKER-050-targeted ligands regulate multiple stages of the thrombopoiesis pathway in mice. Additionally, our data demonstrate that KER-050 has the potential to accelerate the rate of PLT recovery due to acute depletion, and could represent a potential novel treatment option for thrombocytopenia in patients with MDS, MF and IT. Disclosures Feigenson: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Nathan: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lamora: Keros Therapeutics: Current Employment. Fisher: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Tseng: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Seehra: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lachey: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.


Sensors ◽  
2021 ◽  
Vol 21 (20) ◽  
pp. 6780
Author(s):  
Zhitong Lai ◽  
Rui Tian ◽  
Zhiguo Wu ◽  
Nannan Ding ◽  
Linjian Sun ◽  
...  

Pyramid architecture is a useful strategy to fuse multi-scale features in deep monocular depth estimation approaches. However, most pyramid networks fuse features only within the adjacent stages in a pyramid structure. To take full advantage of the pyramid structure, inspired by the success of DenseNet, this paper presents DCPNet, a densely connected pyramid network that fuses multi-scale features from multiple stages of the pyramid structure. DCPNet not only performs feature fusion between the adjacent stages, but also non-adjacent stages. To fuse these features, we design a simple and effective dense connection module (DCM). In addition, we offer a new consideration of the common upscale operation in our approach. We believe DCPNet offers a more efficient way to fuse features from multiple scales in a pyramid-like network. We perform extensive experiments using both outdoor and indoor benchmark datasets (i.e., the KITTI and the NYU Depth V2 datasets) and DCPNet achieves the state-of-the-art results.


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