Utilizing Slow Reading Techniques to Promote Deep Learning

Slow reading has long been viewed as a teaching technique that engages students more deeply with course readings. Little systematic research, however, has been done to understand how this pedagogical strategy works in college classrooms. This study investigated how slow reading techniques promoted deep learning among undergraduate college students across two disciplines. Utilizing two food essays as the basis for a reading assignment, students in two courses participated in an intentionally scaffolded and paced slow reading exercise designed to encourage deeper personal engagement with course concepts. Theoretical implications from the research demonstrate connections between slow reading techniques and the existing literature on both significant and deep learning. More practically, this study found that slow reading techniques fostered personal storytelling as a means of developing deeper connections to assigned texts, presenting an opportunity for instructors hoping to facilitate the meaningful integration of course concepts into students’ lives

Position paper: Rapid responses to steroids: current status and future prospects.

Steroids exert their actions through several pathways. The classical genomic pathway, which involves binding of steroids to receptors and subsequent modulation of gene expression, is well characterized. Besides this, rapid actions of steroids have been shown to exist. Since 30 years, research on rapid actions of steroids is an emerging field of science. Today, rapid effects of steroids are well established, and are shown to exist for every type of steroid. The classical steroid receptors have been shown to be involved in rapid actions, but there is also strong evidence that unrelated structures mediate these rapid effects. Despite increasing knowledge about the mechanisms and structures which mediate these actions, there is still no unanimous acceptance of this category. This article briefly reviews the history of the field including current controversies and challenges. It is not meant as a broad review of literature, but should increase the awareness of the endocrinology society for rapid responses to steroids. As members of the organizing committee of the VI International Meeting on Rapid Responses to Steroid Hormones 2009, we propose a research agenda focusing on the identification of new receptoral structures and the identification of mechanisms of actions at physiological steroid concentrations. Additionally, efforts for the propagation of translational studies, which should finally lead to clinical benefit in the area of rapid steroid action research, should be intensified

Exploring the Factors Contributing to the High Ultimate pH of Broiler Pectoralis Major Muscles Affected by Wooden Breast Condition

The elevated ultimate pH (pHu) found in wooden breast (WB) meat suggests an altered muscular energetic status in WB but also could be related to a prematurely terminated post-mortem pH decline. The aims of this study were to explore the factors contributing to the elevated pHu and establish whether the occurrence of WB defect alters muscle post-mortem carbohydrate metabolism and determine if the contractile apparatus reflects such changes. A total of 24 carcasses from Ross 308 male chickens were obtained from a commercial producer and harvested using commercial processing procedures. Carcasses were categorized into unaffected (NORM) and WB groups (n = 12 each), and samples were collected from cranial bone-in pectoralis major (PM) muscles at 15 min and 24 h post-mortem for the determination of pH, glycolytic metabolites, adenonucleotides, buffering capacity, phosphofructokinase (PFK) activity, and in vitro pH decline. Twenty-four additional deboned PM samples (12 NORM and 12 WB) were collected from the same processing plant to assess muscle histology and sarcomere length at four different locations throughout the PM muscle. Data show that the reduced glycolytic potential of WB muscles only partially explains the higher (P < 0.001) pHu of WB meat, as residual glycogen along with unaltered PFK activity suggests that neither glycogen nor a deficiency of PFK is responsible for arresting glycolysis prematurely. The dramatic reduction in ATP concentrations in the early post-mortem period suggests a defective ATP-generating pathway that might be responsible for the reduced pH decline in WB samples. Further, the addition of excess of ATPase extended post-mortem glycolysis of WB meat in an in vitro glycolytic system. WB-affected samples have longer (P < 0.001) sarcomeres compared to NORM, indicating the existence of compromised energy-generating pathways in myopathic muscles that may have had consequences on the muscle contraction and tension development, as in vivo, also during the post-mortem period. Considering the overall reduced glycolytic potential and the myodegenerative processes associated with WB condition, we speculate that the higher pHu of WB meat might be the outcome of a drastically impaired energy-generating pathway combined with a deficiency and/or a dysfunction of muscle ATPases, having consequences also on muscle fiber contraction degree

An Automated Machine Learning-based Model Predicts Postoperative Mortality Using Readily-Extractable Preoperative Electronic Health Record Data

Background Rapid, preoperative identification of patients with the highest risk for medical complications is necessary to ensure that limited infrastructure and human resources are directed towards those most likely to benefit. Existing risk scores either lack specificity at the patient level or utilise the American Society of Anesthesiologists (ASA) physical status classification, which requires a clinician to review the chart. Methods We report on the use of machine learning algorithms, specifically random forests, to create a fully automated score that predicts postoperative in-hospital mortality based solely on structured data available at the time of surgery. Electronic health record data from 53 097 surgical patients (2.01% mortality rate) who underwent general anaesthesia between April 1, 2013 and December 10, 2018 in a large US academic medical centre were used to extract 58 preoperative features. Results Using a random forest classifier we found that automatically obtained preoperative features (area under the curve [AUC] of 0.932, 95% confidence interval [CI] 0.910–0.951) outperforms Preoperative Score to Predict Postoperative Mortality (POSPOM) scores (AUC of 0.660, 95% CI 0.598–0.722), Charlson comorbidity scores (AUC of 0.742, 95% CI 0.658–0.812), and ASA physical status (AUC of 0.866, 95% CI 0.829–0.897). Including the ASA physical status with the preoperative features achieves an AUC of 0.936 (95% CI 0.917–0.955). Conclusions This automated score outperforms the ASA physical status score, the Charlson comorbidity score, and the POSPOM score for predicting in-hospital mortality. Additionally, we integrate this score with a previously published postoperative score to demonstrate the extent to which patient risk changes during the perioperative period

Galaxy Cluster Pressure Profiles as Determined by Sunyaev Zel’dovich Effect Observations with MUSTANG and Bolocam. II. Joint Analysis of 14 Clusters

We present pressure profiles of galaxy clusters determined from high resolution Sunyaev-Zel'dovich (SZ) effect observations of fourteen clusters, which span the redshift range $0.25 < z < 0.89$. The procedure simultaneously fits spherical cluster models to MUSTANG and Bolocam data. In this analysis, we adopt the generalized NFW parameterization of pressure profiles to produce our models. Our constraints on ensemble-average pressure profile parameters, in this study $\gamma$, $C_{500}$, and $P_0$, are consistent with those in previous studies, but for individual clusters we find discrepancies with the X-ray derived pressure profiles from the ACCEPT2 database. We investigate potential sources of these discrepancies, especially cluster geometry, electron temperature of the intracluster medium, and substructure. We find that the ensemble mean profile for all clusters in our sample is described by the parameters: $[\gamma,C_{500},P_0] = [0.3_{-0.1}^{+0.1}, 1.3_{-0.1}^{+0.1}, 8.6_{-2.4}^{+2.4}]$, for cool core clusters: $[\gamma,C_{500},P_0] = [0.6_{-0.1}^{+0.1}, 0.9_{-0.1}^{+0.1}, 3.6_{-1.5}^{+1.5}]$, and for disturbed clusters: $[\gamma,C_{500},P_0] = [0.0_{-0.0}^{+0.1}, 1.5_{-0.2}^{+0.1},13.8_{-1.6}^{+1.6}]$. Four of the fourteen clusters have clear substructure in our SZ observations, while an additional two clusters exhibit potential substructure.Comment: 22 pages, 9 figures, accepted to Ap

Mutation of neuron-specific chromatin remodeling subunit BAF53b:rescue of plasticity and memory by manipulating actin remodeling

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53b Delta SB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53b Delta SB2 mice in an effort to rescue LTP and memory. BAF53b Delta SB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders

Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection

The ArcA regulon and oxidative stress resistance in Haemophilus influenzae

Haemophilus influenzae transits between niches within the human host that are predicted to differ in oxygen levels. The ArcAB two-component signal transduction system controls gene expression in response to respiratory conditions of growth and has been implicated in bacterial pathogenesis, yet the mechanism is not understood. We undertook a genome-scale study to identify genes of the H. influenzae ArcA regulon. Deletion of arcA resulted in increased anaerobic expression of genes of the respiratory chain and of H. influenzae's partial tricarboxylic acid cycle, and decreased anaerobic expression levels of genes of polyamine metabolism, and iron sequestration. Deletion of arcA also conferred a susceptibility to transient exposure to hydrogen peroxide that was greater following anaerobic growth than after aerobic growth. Array data revealed that the dps gene, not previously assigned to the ArcA modulon in bacteria, exhibited decreased expression in the arcA mutant. Deletion of dps resulted in hydrogen peroxide sensitivity and complementation restored resistance, providing insight into the previously uncharacterized mechanism of arcA-mediated H2O2 resistance. The results indicate a role for H. influenzae arcA and dps in pre-emptive defence against transitions from growth in low oxygen environments to aerobic exposure to hydrogen peroxide, an antibacterial oxidant produced by phagocytes during infection

Genome-Wide Analysis of Transcriptional Reprogramming in Mouse Models of Acute Myeloid Leukaemia

Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML) using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation that were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors including Gata2, Gfi1 and Sfpi1/Pu.1. In particular, downregulation of Gata2 expression was mirrored by abundant GATA motifs in regions of reduced histone acetylation suggesting an important role in leukaemogenic transcriptional reprogramming. Forced re-expression of Gata2 was not compatible with sustained growth of leukaemic cells thus suggesting a previously unrecognised role for Gata2 in downregulation during the development of AML. Additionally, large scale human AML datasets revealed significantly higher expression of GATA2 in CD34+ cells from healthy controls compared with AML blast cells. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes

Background: The aim of this study in patients with acute posterior ischemic stroke (PS) and atrial fibrillation (AF) were to evaluate the risks of recurrent ischemic event and severe bleeding and these risks in relation with oral anticoagulant therapy (OAT) and its timing. Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of: stroke recurrence, TIA, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2,470 patients were available for the analysis: 473 (19.1%) with PS and 1,997 (80.9%) AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Conclusions: Patients with posterior or anterior stroke and AF appear to have similar risks of ischemic or hemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT