Phenotypic Variability and Paternal Inheritance of a CHD8 Variant Causing Intellectual Developmental Disorder With Autism and Macrocephaly Confirmed by Epigenetic and Structural Analyses

ABSTRACT Background Intellectual developmental disorder with autism and macrocephaly (IDDAM, OMIM #615032) is an autosomal dominant neurodevelopmental disorder characterized primarily by intellectual disability, autism spectrum disorder, macrocephaly, tall stature, gastrointestinal symptoms, and variable neurological manifestations. Most cases result from de novo pathogenic variants in CHD8 . Methods We conducted genome sequencing through the Undiagnosed Diseases Network (UDN) in a female proband harboring a CHD8 variant of uncertain significance (VUS), whose clinical presentation was consistent with IDDAM but included atypical features such as ptosis and hearing loss. Variant pathogenicity was further evaluated using EpiSign DNA methylation analysis and structural biology modeling. Results Genome sequencing confirmed the CHD8 variant inherited from her father, who exhibited a subtle feature, including traits consistent with attention‐deficit/hyperactivity disorder. Pathogenicity was confirmed through epigenetic signature testing (EpiSign), demonstrating characteristic methylation patterns and structural biology analysis, predicting significant protein destabilization. Conclusion We describe the case of IDDAM caused by a paternally inherited CHD8 variant. Our findings highlight the importance of considering parental inheritance in IDDAM diagnoses and suggest epigenetic and structural biology analyses as valuable tools for reclassifying VUS when variant pathogenicity remains uncertain.

Amplify Your Mission with Data‐Driven Stories

A New Polar Representation and Identities for Split Leonardo Quaternions

ABSTRACT In this study, we define split Leonardo quaternion sequences with components involving Leonardo numbers. We give fundamental properties and identities associated with split Leonardo quaternions, such as Binet's formula, as well as identities attributed to Catalan, Cassini, and d'Ocagne. Furthermore, we introduce an innovative concept: polar representation for these split quaternions using Cayley Dickson's notation. This alternative representation provides a new perspective on the structure of split Leonardo quaternions and give a deeper understanding of their geometric interpretations and transformations.

The tentacles of surveillance: Cephalopods and United States satellite intelligence

Abstract This article examines the symbol placed on a US spy satellite, National Reconnaissance Office Launch–39 (NROL‐39). In 2013, NROL‐39 was launched into space, the payload vehicle and mission patch emblazoned with a gigantic octopus, its tentacles surrounding the globe, and the words “Nothing Is Beyond Our Reach” written below the globe. Spy satellites are not new, but what is new here is the explicit use of a known symbol of threat and domination by a United States intelligence agency and the stories it crafts around fear and domination. NROL‐39 is an insight into how a US intelligence organization pictures itself, its role, and its targets. NROL‐39 gives us a glimpse behind the mask of the security state and what this tells us about the worldview and political imaginaries of the people behind it. The use of a symbol traditionally associated with political repression and threat gives us insight into how security officials think about satellites, intelligence collection, security, domination, and enemies. It is an opening into the militarized imaginary of satellite intelligence, technological capabilities, propaganda and psychological operations, and the further militarization and politicization of space.

Mission Abort Policy Considering Imperfect Alarms and Two Abort Options

ABSTRACT A mission may be aborted during operation to increase the likelihood of system survival when an alarm system indicates that the system has entered a defect state. However, due to measurement and environmental noise, missed and false alarms frequently occur during online condition monitoring, complicating the decision‐making process for mission abort. Additionally, once a mission is aborted, various rescue procedures can be initiated. This study addresses these challenges by proposing a partially observable Markov decision process (POMDP) framework aimed at minimizing the expected total cost associated with mission and system failures. Within this framework, the probability that the system is in a defect state is dynamically updated using real‐time signals from the alarm system. We demonstrate that the optimal mission abort policy follows a control limit policy, where a mission should be aborted when the defect probability exceeds a certain threshold during each period. To illustrate the effectiveness of the proposed policy, we present a case study on an unmanned aerial vehicle (UAV).

When bringing on new board members, an effective orientation program can help them hit the ground running

Typically, nonprofit boards looking to fill slots on the board will seek out new recruits with professional experience, wide (and preferably affluent) social circles and varied political and sociological perspectives. But that doesn't necessarily mean they will be fluent in the organization's mission, program areas and the more specific details of board service.

Maximize this year's GivingTuesday with help from your board

With fall and winter fast approaching, the mission‐critical end‐of‐year fundraising season is coming into view for many nonprofits. And as in previous years, a major kickstart to these campaigns is GivingTuesday, a global day of generosity that has grown by leaps and bounds over the last few years, now accounting for some $3.6 billion in donations to nonprofits globally, 2024 data show.

New initiative shines light on need to fund 501(c)(4) activities

These days, funders of all stripes are searching for ways to help their grantees and other nonprofits weather—or even fight back against—the chaos that has accompanied the new Trump administration and its efforts to claw back funding and impose its will on all types of institutions. For Mission Telecom, a provider of telecommunications services, the answer lies in providing funding for outright political activities—so‐called 501(c)(4) funding—a rarity for grantmakers since this kind of donation doesn't offer the same tax deductibility advantages as donations to traditional 501(c)(3) groups.

Leverage constituent feedback to improve governance, board operations

Experts in nonprofit governance agree that having direct feedback from an organization's end users and constituents can help their boards make better‐informed decisions about programming, operations and long‐term progress towards their mission.

An Exact Algorithm for the Hazardous Orienteering Problem

ABSTRACT The hazardous orienteering problem is the topic of this study. It is a variant of the well‐studied orienteering problem, where a vehicle, given a maximum mission time, has to select and visit customers out of a set of requests, aiming at maximizing the total profit associated with the customers selected. In the hazardous version of the problem we consider, the customers are associated with parcels that have to be collected, and some of them might explode during the transportation, after having been picked up. The probability of explosion depends on the characteristics of the parcel and on the time spent by the dangerous parcel itself on the vehicle. If an explosion happens, the collected profit is totally lost. The target becomes then to select the tour that maximizes the expected profit, taking into account the probability of catastrophic events happening. In this article, we propose an exact solving approach based on a mixed integer linear programming model which is dynamically modified by adding new constraints. The computational results substantially improve the state‐of‐the‐art for the problem.