Frontal Hypoactivation During a Working Memory Task in Children With 22q11 Deletion Syndrome

Impairments in executive function, such as working memory, are almost universal in children with chromosome 22q11.2 deletion syndrome. Delineating the neural underpinnings of these functions would enhance understanding of these impairments. In this study, children and adolescents with 22q11 deletion syndrome were compared with healthy control participants in an fMRI study of working memory. When the 2-back condition was contrasted with the 1-back and 0-back conditions, the participants with 22q11 deletion syndrome showed lower activation in several brain areas involved in working memory—notably dorsolateral prefrontal cortex, anterior cingulate, and precuneus. This hypoactivation may be due to reduced gray matter volumes or white matter connectivity in frontal and parietal regions, differences that have previously been documented in children with 22q11 deletion syndrome. Understanding differences in brain function will provide a foundation for future interventions to address the wide range of neurodevelopmental deficits observed in 22q11 deletion syndrome

Containerization on Petascale HPC Clusters

Containerization technologies provide a mechanism to encapsulate applications and many of their dependencies, facilitating software portability and reproducibility on HPC systems. However, in order to access many of the architectural features that enable HPC system performance, compatibility between certain components of the container and host are required, resulting in a trade-off between portability and performance. In this work, we discuss our early experiences running three state-of-the-art containerization technologies on the petascale Frontera system. We present how we build the containers to ensure performance and security and their performance at scale.We ran microbenchmarks at a scale of 4,096 nodes and demonstrate the near-native performance and minimal memory overheads by the containerized environments at 70,000 processes on 1,296 nodes with a scientific application MILC - a quantum chromodynamics code.UT Austin-Portugal Program, a collaboration between the Portuguese Foundation of Science and Technology and the University of Texas at Austin, award UTA18-001217Texas Advanced Computing Center (TACC

PADLL: Taming Metadata-intensive HPC Jobs Through Dynamic, Application-agnostic QoS Control

Modern I/O applications that run on HPC infrastructures are increasingly becoming read and metadata intensive. However, having multiple concurrent applications submitting large amounts of metadata operations can easily saturate the shared parallel file system's metadata resources, leading to overall performance degradation and I/O unfairness. We present PADLL, an application and file system agnostic storage middleware that enables QoS control of data and metadata workflows in HPC storage systems. It adopts ideas from Software-Defined Storage, building data plane stages that mediate and rate limit POSIX requests submitted to the shared file system, and a control plane that holistically coordinates how all I/O workflows are handled. We demonstrate its performance and feasibility under multiple QoS policies using synthetic benchmarks, real-world applications, and traces collected from a production file system. Results show that PADLL can enforce complex storage QoS policies over concurrent metadata-aggressive jobs, ensuring fairness and prioritization.Comment: To appear at 23rd IEEE/ACM International Symposium on Cluster, Cloud and Internet Computing (CCGrid'23

Risk-Adjusted Survival after Coronary Artery Bypass Grafting: Implications for Quality Improvement

Mortality represents an important outcome measure following coronary artery bypass grafting. Shorter survival times may reflect poor surgical quality and an increased number of costly postoperative complications. Quality control efforts aimed at increasing survival times may be misleading if not properly adjusted for case-mix severity. This paper demonstrates how to construct and cross-validate efficiency-outcome plots for a specified time (e.g., 6-month and 1-year survival) after coronary artery bypass grafting, accounting for baseline cardiovascular risk factors. The application of this approach to regional centers allows for the localization of risk stratification rather than applying overly broad and non-specific models to their patient populations

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Feasibility and preliminary efficacy data from a computerized cognitive intervention in children with chromosome 22q11.2 deletion syndrome

Children with chromosome 22q11.2 deletion syndrome (22q11DS) are significantly impaired in their academic performance and functionality due to cognitive deficits, especially in attention, memory, and other facets of executive function. Compounding these cognitive deficits is the remarkably high risk of major psychoses, occurring in 25% of adolescents and adults with the disorder. There are currently no evidence-based interventions designed to improve the cognitive deficits in these individuals. We implemented a neuroplasticity-based computerized cognitive remediation program for 12 weeks in 13 adolescents with 22q11DS, assessed feasibility, and measured changes in cognition before and after the intervention compared to a control group of 10 age- and gender-matched children with 22q11DS. Our results indicated that despite their cognitive impairments, this intervention is feasible in children with 22q11DS, with high rates of adherence and satisfaction. Our preliminary analyses indicate that gains in cognition occur with the intervention. Further study in a larger randomized controlled trial would enable assessment of efficacy of this novel intervention

Applicability of the Nonverbal Learning Disability Paradigm for Children With 22q11.2 Deletion Syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion in humans. Nonverbal learning disability (NLD) has been used to describe the strengths and deficits of children with 22q11DS, but the applicability of the label for this population has seldom been systematically evaluated. The goal of the current study was to address how well the NLD diagnosis characterizes children and adolescents with 22q11DS. A total of 74 children and adolescents with 22q11DS were given neurocognitive, socioemotional, and academic assessments to measure aspects of NLD. Of the cohort, 20% met at least 7 of 9 assessed criteria for NLD; 25% showed verbal skills exceeding their nonverbal skills as assessed by an IQ test; and 24% showed the good rote verbal capacity commonly associated with NLD. Hypothesizing that if the entire cohort did not show consistent NLD characteristics, the descriptor might be more accurate for a distinct subgroup, the authors used latent class analysis to divide participants into three subgroups. However, the lines along which the groups broke out were more related to general functioning level than to NLD criteria. All three groups showed a heightened risk for psychiatric illness, highlighting the importance of careful mental health monitoring for all children with 22q11DS

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Tripodal transmembrane transporters for bicarbonate

Easy-to-make tripodal tris-thiourea receptors based upon tris(2-aminoethyl)amine are capable of chloride/bicarbonate transport and as such represent a new class of bicarbonate transport agent.<br/

Standard Colonic Lavage Alters the Natural State of Mucosal-Associated Microbiota in the Human Colon

Past studies of the human intestinal microbiota are potentially confounded by the common practice of using bowel-cleansing preparations. We examined if colonic lavage changes the natural state of enteric mucosal-adherent microbes in healthy human subjects.Twelve healthy individuals were divided into three groups; experimental group, control group one, and control group two. Subjects in the experimental group underwent an un-prepped flexible sigmoidoscopy with biopsies. Within two weeks, subjects were given a standard polyethylene glycol-based bowel cleansing preparation followed by a second flexible sigmoidoscopy. Subjects in control group one underwent two un-prepped flexible sigmoidoscopies within one week. Subjects in the second control group underwent an un-prepped flexible sigmoidoscopy followed by a second flexible sigmoidoscopy after a 24-hour clear liquid diet within one week. The mucosa-associated microbial communities from the two procedures in each subject were compared using 16S rRNA gene based terminal restriction fragment length polymorphism (T-RFLP), and library cloning and sequencing.Clone library sequencing analysis showed that there were changes in the composition of the mucosa-associated microbiota in subjects after colonic lavage. These changes were not observed in our control groups. Standard bowel preparation altered the diversity of mucosa-associated microbiota. Taxonomic classification did not reveal significant changes at the phylum level, but there were differences observed at the genus level.Standard bowel cleansing preparation altered the mucosal-adherent microbiota in all of our subjects, although the degree of change was variable. These findings underscore the importance of considering the confounding effects of bowel preparation when designing experiments exploring the gut microbiota