Behind The Design

Higher education is a place of learning and such a space requires the optimal design for a learning setting. While classrooms are an important space for learning in higher education, they are not the only place, where learning occurs on campuses. These spaces outside of the classroom are referred to in ways such as “private study areas”, “writing centers,” and “third spaces”, but in this paper, these spaces are referred to as informal study spaces. These spaces are identified as any space, outside of a formal classroom setting, where students regularly congregate for academic purposes. Eastern Kentucky University (EKU) has a myriad of informal study spaces, old and new, spread throughout the Richmond, KY campus. In order to narrow the study and develop area-specific observations, this study focuses on three select informal study spaces on EKU campus. The informal study spaces analyzed include the Noel Studio, the Powell Student Center, and the Center for STEM Excellence. This research seeks to highlight the history of the identified informal study spaces, their progress through design, and the design\u27s impact on the users of the spaces. The study also identifies what students and staff envision for the future of these spaces. To gain both the staff and student perspectives, a student survey is implemented alongside in-depth interviews, which are administered to voluntary faculty respondents. The progress of the design intents and impacts, significant and observable behaviors, thought processes, or changes in the observed parties, are documented in an ephemera book to give members of EKU tangible documentation of this research

Dose de-escalation of intrapleural tissue plasminogen activator therapy for pleural infection. The alteplase dose assessment for Pleural infection Therapy project

Rationale: Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. Objectives: To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Methods: Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. Results: We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22–58] to 16% [8–31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247–2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent surgery. Three patients (4.9%) received blood transfusions for gradual pleural blood loss; none were hemodynamically compromised. Pain requiring escalation of analgesia affected 36% of patients; none required cessation of therapy. Conclusions: These pilot data suggest that a starting dose of 5 mg of tPA administered intrapleurally twice daily in combination with 5 mg of DNase for the treatment of pl

Synuclein deficiency results in age-related respiratory and cardiovascular dysfunctions in mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging

Broad Line Emission in Low-Metallicity Blue Compact Dwarf Galaxies: Evidence for Stellar Wind, Supernova and Possible AGN Activity

We present spectra of a large sample of low-metallicity blue compact dwarf galaxies which exhibit broad components in their strong emission lines, mainly in Hbeta, [O III]4959, 5007 and Halpha. Twenty-three spectra have been obtained with the MMT, 14 of which show broad emission. The remaining 21 spectra with broad emission have been selected from the Data Release 5 of the Sloan Digital Sky Survey. The most plausible origin of broad line emission is the evolution of massive stars and their interaction with the circumstellar and interstellar medium. The broad emission with the lowest H$\alpha$ luminosities (10^36 - 10^39 erg/s) is likely produced in circumstellar envelopes around hot Ofp/WN9 and/or LBV stars. The broad emission with the highest Halpha luminosities (10^40 - 10^42 erg/s) probably arises from type IIp or type IIn supernovae (SNe). It can also come from active galactic nuclei (AGN) containing intermediate-mass black holes, although we find no strong evidence for hard non-thermal radiation in our sample galaxies. The oxygen abundance in the host galaxies with SN candidates is low and varies in the range 12 + log O/H = 7.36 - 8.31. However, type IIn SN / AGN candidates are found only in galaxies with 12 + log O/H < 7.99. Spectroscopic monitoring of these type IIn SN / AGN candidates over a time scale of several years is necessary to distinguish between the two possibilities.Comment: 50 pages, 6 figures. Accepted for publication in the Astrophysical Journa

Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

<p>Abstract</p> <p>Background</p> <p>Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels) play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes.</p> <p>Results</p> <p>Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i) those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb) region, (ii) those with at least one exact copy found nearby, and (iii) those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429) were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans.</p> <p>Conclusion</p> <p>Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are substantial differences in representation of indel classes among genomic elements, most likely caused by differences in their evolutionary histories. Using local sequence context, we predicted origins and phylogenetic relationships of gene-impacting indels in primate species. These results suggest that genome plasticity is a major force behind speciation events separating the great ape lineages.</p

Reduced monocyte and macrophage TNFSF15/TL1A expression is associated with susceptibility to inflammatory bowel disease.

Chronic inflammation in inflammatory bowel disease (IBD) results from a breakdown of intestinal immune homeostasis and compromise of the intestinal barrier. Genome-wide association studies have identified over 200 genetic loci associated with risk for IBD, but the functional mechanisms of most of these genetic variants remain unknown. Polymorphisms at the TNFSF15 locus, which encodes the TNF superfamily cytokine commonly known as TL1A, are associated with susceptibility to IBD in multiple ethnic groups. In a wide variety of murine models of inflammation including models of IBD, TNFSF15 promotes immunopathology by signaling through its receptor DR3. Such evidence has led to the hypothesis that expression of this lymphocyte costimulatory cytokine increases risk for IBD. In contrast, here we show that the IBD-risk haplotype at TNFSF15 is associated with decreased expression of the gene by peripheral blood monocytes in both healthy volunteers and IBD patients. This association persists under various stimulation conditions at both the RNA and protein levels and is maintained after macrophage differentiation. Utilizing a "recall-by-genotype" bioresource for allele-specific expression measurements in a functional fine-mapping assay, we localize the polymorphism controlling TNFSF15 expression to the regulatory region upstream of the gene. Through a T cell costimulation assay, we demonstrate that genetically regulated TNFSF15 has functional relevance. These findings indicate that genetically enhanced expression of TNFSF15 in specific cell types may confer protection against the development of IBD

Is an opportunistic primary care-based intervention for non-responders to bowel screening feasible and acceptable?:A mixed-methods feasibility study in Scotland

Objectives We aimed to test whether a brief, opportunistic intervention in general practice was a feasible and acceptable way to engage with bowel screening non-responders. Design This was a feasibility study testing an intervention which comprised a brief conversation during routine consultation, provision of a patient leaflet and instructions to request a replacement faecal occult blood test kit. A mixed-methods approach to evaluation was adopted. Data were collected from proformas completed after each intervention, from the Bowel Screening Centre database and from questionnaires. Semi-structured interviews were carried out. We used descriptive statistics, content and framework analysis to determine intervention feasibility and acceptability. Participants Bowel screening non-responders (as defined by the Scottish Bowel Screening Centre) and primary care professionals working in five general practices in Lothian, Scotland. Primary and secondary outcome measures Several predefined feasibility parameters were assessed, including numbers of patients engaging in conversation, requesting a replacement kit and returning it, and willingness of primary care professionals to deliver the intervention. Results The intervention was offered to 258 patients in five general practices: 220 (87.0%) engaged with the intervention, 60 (23.3%) requested a new kit, 22 (8.5%) kits were completed and returned. Interviews and questionnaires suggest that the intervention was feasible, acceptable and consistent with an existing health prevention agenda. Reported challenges referred to work-related pressures, time constraints and practice priorities. Conclusions This intervention was acceptable and resulted in a modest increase in non-responders participating in bowel screening, although outlined challenges may affect sustained implementation. The strategy is also aligned with the increasing role of primary care in promoting bowel screening

Risk of Orthostatic Intolerance During Re-Exposure to Gravity

Post-spaceflight orthostatic intolerance remains a significant concern to NASA. In Space Shuttle missions, astronauts wore anti-gravity suits and liquid cooling garments to protect against orthostatic intolerance during re-entry and landing, but in-flight exercise and the end-of-mission fluid loading failed to protect approximately 30% of Shuttle astronauts when these garments were not worn. The severity of the problem appears to be increased after long-duration space flight. Five of six US astronauts could not complete a 10-minutes upright-posture tilt testing on landing day following 4-5 month stays aboard the Mir space station. The majority of these astronauts had experienced no problems of orthostatic intolerance following their shorter Shuttle flights. More recently, four of six US astronauts could not complete a tilt test on landing day following approximately 6 month stays on the International Space Station. Similar observations were made in the Soviet and Russian space programs, such that some cosmonauts wear the Russian compression garments (Kentavr) up to 4 days after landing. Future exploration missions, such as those to Mars or Near Earth Objects, will be long duration, and astronauts will be landing on planetary bodies with no ground-support teams. The occurrence of severe orthostatic hypotension could threaten the astronauts' health and safety and success of the mission

In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants

Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42–100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19–95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally