Evidence for Coupling of Velocity and Composition Fluctuations in a Binary Liquid Mixture

A critical mixture of isobutyric acid and water was quenched from the one-phase region into the two-phase region and, after the spinodal ring was well developed, a reverse quench returned the system to the one-phase region. Light-scattering measurements for this process exhibit a clearly nondiffusive relaxation which, at least for early times after the quench reversal, is in good agreement with Ruiz\u27s scheme for the coupling of velocity and composition fluctuations

Using Novel Carbon Monoxide Devices in Remote Smoking Cessation Treatment: A Utilization and Reliability Analysis

https://openworks.mdanderson.org/sumexp22/1119/thumbnail.jp

Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique junctions. To characterize these somatic variants and their associated splice isoforms, we annotate them with the Variant Effect Predictor, SpliceAI, and Genotype-Tissue Expression junction counts and compare our results to other tools that integrate genomic and transcriptomic data. While many events are corroborated by the aforementioned tools, the flexibility of RegTools also allows us to identify splice-associated variants in known cancer drivers, such as TP53, CDKN2A, and B2M, and other genes

Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

From PALSA PLUS to PALM PLUS: adapting and developing a South African guideline and training intervention to better integrate HIV/AIDS care with primary care in rural health centers in Malawi

<p>Abstract</p> <p>Background</p> <p>Only about one-third of eligible HIV/AIDS patients receive anti-retroviral treatment (ART). Decentralizing treatment is crucial to wider and more equitable access, but key obstacles are a shortage of trained healthcare workers (HCW) and challenges integrating HIV/AIDS care with other primary care. This report describes the development of a guideline and training program (PALM PLUS) designed to integrate HIV/AIDS care with other primary care in Malawi. PALM PLUS was adapted from PALSA PLUS, developed in South Africa, and targets middle-cadre HCWs (clinical officers, nurses, and medical assistants). We adapted it to align with Malawi's national treatment protocols, more varied healthcare workforce, and weaker health system infrastructure.</p> <p>Methods/Design</p> <p>The international research team included the developers of the PALSA PLUS program, key Malawi-based team members and personnel from national and district level Ministry of Health (MoH), professional associations, and an international non-governmental organization. The PALSA PLUS guideline was extensively revised based on Malawi national disease-specific guidelines. Advice and input was sought from local clinical experts, including middle-cadre personnel, as well as Malawi MoH personnel and representatives of Malawian professional associations.</p> <p>Results</p> <p>An integrated guideline adapted to Malawian protocols for adults with respiratory conditions, HIV/AIDS, tuberculosis, and other primary care conditions was developed. The training program was adapted to Malawi's health system and district-level supervision structure. PALM PLUS is currently being piloted in a cluster-randomized trial in health centers in Malawi (ISRCTN47805230).</p> <p>Discussion</p> <p>The PALM PLUS guideline and training intervention targets primary care middle-cadre HCWs with the objective of improving HCW satisfaction and retention, and the quality of patient care. Successful adaptations are feasible, even across health systems as different as those of South Africa and Malawi.</p

Left versus right subcallosal cingulate deep brain stimulation for treatment-resistant depression

Deep brain stimulation (DBS) of the subcallosal cingulate has emerged as a promising therapy for treatment-resistant depression (TRD). To date, all studies have employed bilateral stimulation; however, the physiology of affect and pathophysiology of depression are known to be asymmetric across hemispheres. Unilateral stimulation may provide efficacy while decreasing risk. Five patients were exposed to unilateral open-label DBS to the subcallosal cingulate for 12 weeks each to the left and then right hemispheres in a double-blind, crossover fashion. After 12 weeks of stimulation to each hemisphere, bilateral stimulation was initiated, and patients were followed for 12 additional weeks. Additionally, nine months of long-term follow up data were collected. Left, but not right, unilateral stimulation was associated with significant decrease in depression scores; with bilateral stimulation, all patients improved and one patient remitted. No serious adverse events were associated with surgery or acute or chronic stimulation. This small study suggests that unilateral DBS to the subcallosal cingulate may be an effective treatment for TRD. All patients improved with bilateral stimulation, though antidepressant effects following 12 weeks were modest. These findings contrast somewhat with prior open-label trials, though duration of bilateral stimulation was shorter in this trial. The current study continues to confirm safety of implantation and use of DBS to the subcallosal cingulate for patients with TRD and highlights the importance of personalization of therapy, for example by hemisphere, in future trials

Locomotion Guidance by Extracellular Matrix Is Adaptive and Can be Restored by a Transient Change in Ca2+ Level

Navigation of cell locomotion by gradients of soluble factors can be desensitized if the concentration of the chemo-attractant stays unchanged. It remains obscure if the guidance by immobilized extracellular matrix (ECM) as the substrate is also adaptive and if so, how can the desensitized ECM guidance be resensitized. When first interacting with a substrate containing micron-scale fibronectin (FBN) trails, highly motile fish keratocytes selectively adhere and migrate along the FBN paths. However, such guided motion become adaptive after about 10 min and the cells start to migrate out of the ECM trails. We found that a burst increase of intracellular calcium created by an uncaging technique immediately halts the undirected migration by disrupting the ECM-cytoskeleton coupling, as evidenced by the appearance of retrograde F-actin flow. When the motility later resumes, the activated integrin receptors render the cell selectively binding to the FBN path and reinitiates signaling events, including tyrosine phosphorylation of paxillin, that couple retrograde F-actin flow to the substrate. Thus, the calcium-resensitized cell can undergo a period of ECM-navigated movement, which later becomes desensitized. Our results also suggest that endogenous calcium transients as occur during spontaneous calcium oscillations may exert a cycling resensitization-desensitization control over cell's sensing of substrate guiding cues