Personalization And Increased Engagement Through Extended Learning Opportunities

This qualitative intrinsic case study of a bounded system examined student perceptions of their experiences with the Extended Learning Opportunities (ELO) program at Hillsboro-Deering High School. The study data derived from interviews with nine individuals who had participated in the ELO program. The study participants were both current students and alumni. The study explored the ELO program as a means of personalization and engaging students in their learning. Five main themes emerged from the data: Personal Interest, Relationships, Motivation, Self-directed and Self-paced, and Program Awareness. The study shows that students valued their experiences in the ELO program and felt that it was well aligned to the school’s core values and articulated mission. The data also showed that study participants do not believe that the majority of students have adequate awareness and understanding of the ELO program to take advantage of it. Further study is recommended to explore student perception of the relationship of grades to learning. Further study is also recommended to examine why some students who enroll in the ELO program do not complete their projects. The study produced several concrete suggestions for how to develop greater awareness and understanding of the program for students. The study provides solid support for the growth and expansion of the ELO program at Hillsboro-Deering High School

Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults.

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa.SIGNIFICANCE STATEMENT Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior

FunnyBase: a systems level functional annotation of Fundulus ESTs for the analysis of gene expression

BACKGROUND: While studies of non-model organisms are critical for many research areas, such as evolution, development, and environmental biology, they present particular challenges for both experimental and computational genomic level research. Resources such as mass-produced microarrays and the computational tools linking these data to functional annotation at the system and pathway level are rarely available for non-model species. This type of "systems-level" analysis is critical to the understanding of patterns of gene expression that underlie biological processes. RESULTS: We describe a bioinformatics pipeline known as FunnyBase that has been used to store, annotate, and analyze 40,363 expressed sequence tags (ESTs) from the heart and liver of the fish, Fundulus heteroclitus. Primary annotations based on sequence similarity are linked to networks of systematic annotation in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and can be queried and computationally utilized in downstream analyses. Steps are taken to ensure that the annotation is self-consistent and that the structure of GO is used to identify higher level functions that may not be annotated directly. An integrated framework for cDNA library production, sequencing, quality control, expression data generation, and systems-level analysis is presented and utilized. In a case study, a set of genes, that had statistically significant regression between gene expression levels and environmental temperature along the Atlantic Coast, shows a statistically significant (P < 0.001) enrichment in genes associated with amine metabolism. CONCLUSION: The methods described have application for functional genomics studies, particularly among non-model organisms. The web interface for FunnyBase can be accessed at . Data and source code are available by request at [email protected]

Determination of polar bear (Ursus maritimus) individual genotype and sex based on DNA extracted from paw-prints in snow

Polar bears rely upon sea ice to hunt, travel, and reproduce. Declining sea ice extent and duration has led polar bears to be designated as “threatened” (ESA). Population monitoring is vital to polar bear conservation; but recently, poor sea ice has made traditional aircraft-based methods less viable. These methods largely rely upon the capture and handling of polar bears, and have been criticized over animal welfare concerns. Monitoring polar bears via DNA sampling is a promising option. One common method utilizes biopsy darts delivered from a helicopter to collect DNA, a method that faces similar ice associated challenges to those described above. However, epidermal cells shed from the foot pads of a polar bear into its paw-prints in snow are a source of “environmental DNA” (e-DNA) that can be collected non-invasively on the sea ice or on land for potential use in population monitoring. Mitochondrial DNA (mt-DNA) is used to assess whether polar bear DNA is present within a snow sample, and nuclear DNA (n-DNA) can identify individuals and their sex. The goal of this investigation was to assess the viability of using e-DNA collected from paw-prints in the snow to identify individual polar bears and their sex. Snow was sampled from 13 polar bear trails (10 paw-prints per trail) on the sea ice in the Chukchi and Beaufort seas along the North Slope of Alaska. Species verification was based on a mt-DNA PCR fragment analysis test. Identification of individuals was accomplished by amplifying a multiplex of seven n-DNA microsatellite loci, and sex was determined by the amelogenin gene sex ID marker. Six of the 13 bear trails sampled (46%) yielded consensus genotypes for five unique males and one female. To our knowledge, this is the first time that polar bears have been individually identified by genotype and sex using e-DNA collected from snow. This method is non-invasive, could be integrated into genetic mark-recapture sampling designs, and addresses some of the current challenges arising from poor sea ice conditions. It also can involve, engage, and empower Indigenous communities in the Arctic, which are greatly affected by polar bear management decisions

Unbiased Metagenomic Sequencing for Pediatric Meningitis in Bangladesh Reveals Neuroinvasive Chikungunya Virus Outbreak and Other Unrealized Pathogens.

The burden of meningitis in low-and-middle-income countries remains significant, but the infectious causes remain largely unknown, impeding institution of evidence-based treatment and prevention decisions. We conducted a validation and application study of unbiased metagenomic next-generation sequencing (mNGS) to elucidate etiologies of meningitis in Bangladesh. This RNA mNGS study was performed on cerebrospinal fluid (CSF) specimens from patients admitted in the largest pediatric hospital, a World Health Organization sentinel site, with known neurologic infections (n = 36), with idiopathic meningitis (n = 25), and with no infection (n = 30), and six environmental samples, collected between 2012 and 2018. We used the IDseq bioinformatics pipeline and machine learning to identify potentially pathogenic microbes, which we then confirmed orthogonally and followed up through phone/home visits. In samples with known etiology and without infections, there was 83% concordance between mNGS and conventional testing. In idiopathic cases, mNGS identified a potential bacterial or viral etiology in 40%. There were three instances of neuroinvasive Chikungunya virus (CHIKV), whose genomes were &gt;99% identical to each other and to a Bangladeshi strain only previously recognized to cause febrile illness in 2017. CHIKV-specific qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 (n = 472) revealed 17 additional CHIKV meningitis cases, exposing an unrecognized meningitis outbreak. Orthogonal molecular confirmation, case-based clinical data, and patient follow-up substantiated the findings. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis, conduct surveillance, and predict outbreaks. The improved patient- and population-level data can inform evidence-based policy decisions.IMPORTANCE Globally, there are an estimated 10.6 million cases of meningitis and 288,000 deaths every year, with the vast majority occurring in low- and middle-income countries. In addition, many survivors suffer from long-term neurological sequelae. Most laboratories assay only for common bacterial etiologies using culture and directed PCR, and the majority of meningitis cases lack microbiological diagnoses, impeding institution of evidence-based treatment and prevention strategies. We report here the results of a validation and application study of using unbiased metagenomic sequencing to determine etiologies of idiopathic (of unknown cause) cases. This included CSF from patients with known neurologic infections, with idiopathic meningitis, and without infection admitted in the largest children's hospital of Bangladesh and environmental samples. Using mNGS and machine learning, we identified and confirmed an etiology (viral or bacterial) in 40% of idiopathic cases. We detected three instances of Chikungunya virus (CHIKV) that were &gt;99% identical to each other and to a strain previously recognized to cause systemic illness only in 2017. CHIKV qPCR of all remaining stored 472 CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital uncovered an unrecognized CHIKV meningitis outbreak. CSF mNGS can complement conventional diagnostic methods to identify etiologies of meningitis, and the improved patient- and population-level data can inform better policy decisions

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms

BACKGROUND: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice. METHODS: A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated. RESULTS: 75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc ?l(-1) (n = 120) and pyuria ?10 wbc ?l(-1) (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc ?l(-1) and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ??-20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing. CONCLUSIONS: Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity

Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and to be targeted to them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that the membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, Bcl-w was loosely attached to the mitochondrial membrane, but it was converted into an integral membrane protein by cytotoxic signals that induce binding of BH3-only proteins, such as Bim, or by the addition of BH3 peptides to lysates. As the structure of Bcl-w has revealed that its COOH-terminal domain occupies the hydrophobic groove where BH3 ligands bind, displacement of that domain by a BH3 ligand would displace the hydrophobic COOH-terminal residues, allowing their insertion into the membrane. To determine whether BH3 ligation is sufficient to induce the enhanced membrane affinity, or to render Bcl-w proapoptotic, we mimicked their complex by tethering the Bim BH3 domain to the NH2 terminus of Bcl-w. The chimera indeed bound avidly to membranes, in a fashion requiring the COOH-terminal domain, but neither promoted nor inhibited apoptosis. These results suggest that ligation of a proapoptotic BH3-only protein alters the conformation of Bcl-w, enhances membrane association, and neutralizes its survival function

Improving stamina and mobility with preop walking in surgical patients with frailty traits -OASIS IV: randomized clinical trial study protocol

BACKGROUND: Frail older surgical patients face more than a two-fold increase in postoperative complications, including myocardial infarction, deep vein thrombosis, pulmonary embolism, pneumonia, ileus, and others. Many of these complications occur because of postoperative loss of stamina and poor mobility. Preoperative exercise may better prepare these vulnerable patients for surgery. We present the protocol for our ongoing randomized trial to assess the impact of a preoperative walking intervention with remote coaching and pedometer on outcomes of stamina (six-minute walk distance- 6MWD) and mobility (postoperative steps) in older adults with frailty traits. METHODS: We will be conducting a randomized clinical trial with a total of 120 patients permitting up to a 33% rate of attrition, to reach a final sample size of 80 (with 40 patients for each study arm). We will include patients who are age 60 or higher, score 4 or greater on the Edmonton Frailty Scale assessment, and will be undergoing a surgical operation that requires a 2 or more night hospital stay to be eligible for our trial. Using block randomization stratified on baseline 6MWD, we will assign patients to wear a pedometer. At the end of three baseline days, an athletic trainer (AT) will provide a daily step count goal reflecting a 10-20% increase from baseline. Subsequently, the AT will call weekly to further titrate the goal or calls more frequently if the patient is not meeting the prescribed goal. Controls will receive general walking advice. Our main outcome is change in 6MWD on postoperative day (POD) 2/3 vs. baseline. We will also collect 6MWD approximately 4 weeks after surgery and daily in-hospital steps. CONCLUSION: If changes in a 6MWD and step counts are significantly higher for the intervention group, we believe this will confirm our hypothesis that the intervention leads to decreased loss of stamina and mobility. Once confirmed, we anticipate expanding to multiple centers to assess the interventional impact on clinical endpoints. TRIAL REGISTRATION: The randomized clinical trial was registered on clinicaltrials.gov under the identifier NCT03892187 on March 27, 2019