The microbiome and the pathophysiology of asthma

Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma

Impulsivity Like Traits and Risky Driving Behaviors Among College Students

The present study examined the predictive effects of five impulsivity-like traits (Premeditation, Perseverance, Sensation Seeking, Negative Urgency, and Positive Urgency) on driving outcomes (driving errors, driving lapses, driving violations, cell phone driving, traffic citations, and traffic collisions). With a convenience sample of 266 college student drivers, we found that each of the impulsivity-like traits was related to multiple risky driving outcomes. Positive Urgency (tendency to act impulsively when experiencing negative affect) was the most robust predictor of risky driving outcomes. Positive Urgency is a relatively newly conceptualized impulsivity-like trait that was not examined in the driving literature previously, suggesting a strong need to further examine its role as a personality trait related to risky driving. These findings generally support the multidimensional assessment of impulsivity-like traits, and they specifically support the addition of Positive Urgency to a list of risk factors for risky driving behaviors

Scaffolds for 3D in vitro culture of neural lineage cells.

Understanding how neurodegenerative disorders develop is not only a key challenge for researchers but also for the wider society, given the rapidly aging populations in developed countries. Advances in this field require new tools with which to recreate neural tissue in vitro and produce realistic disease models. This in turn requires robust and reliable systems for performing 3D in vitro culture of neural lineage cells. This review provides a state of the art update on three-dimensional culture systems for in vitro development of neural tissue, employing a wide range of scaffold types including hydrogels, solid porous polymers, fibrous materials and decellularised tissues as well as microfluidic devices and lab-on-a-chip systems. To provide some context with in vivo development of the central nervous system (CNS), we also provide a brief overview of the neural stem cell niche, neural development and neural differentiation in vitro. We conclude with a discussion of future directions for this exciting and important field of biomaterials research

Testing of the Trim Tab Parametric Model in NASA Langley's Unitary Plan Wind Tunnel

In support of NASA's Entry, Descent, and Landing technology development efforts, testing of Langley's Trim Tab Parametric Models was conducted in Test Section 2 of NASA Langley's Unitary Plan Wind Tunnel. The objectives of these tests were to generate quantitative aerodynamic data and qualitative surface pressure data for experimental and computational validation and aerodynamic database development. Six component force-and-moment data were measured on 38 unique, blunt body trim tab configurations at Mach numbers of 2.5, 3.5, and 4.5, angles of attack from -4deg to +20deg, and angles of sideslip from 0deg to +8deg. Configuration parameters investigated in this study were forebody shape, tab area, tab cant angle, and tab aspect ratio. Pressure Sensitive Paint was used to provide qualitative surface pressure mapping for a subset of these flow and configuration variables. Over the range of parameters tested, the effects of varying tab area and tab cant angle were found to be much more significant than varying tab aspect ratio relative to key aerodynamic performance requirements. Qualitative surface pressure data supported the integrated aerodynamic data and provided information to aid in future analyses of localized phenomena for trim tab configurations

Tailored emulsion-templated porous polymer scaffolds for iPSC-derived human neural precursor cell culture

The work here describes the synthesis of tailor-made, porous, polymeric materials with elastic moduli in the range associated with mammalian brain tissue (0.1–24 kPa). Three new emulsion-templated porous polymer materials (polyHIPEs) were synthesised by thiol–ene photopolymerisation from hexanediol diacrylate (HDDA) and polyethylene glycol diacrylate (PEGDA) crosslinkers and compared with a previously reported material prepared from trimethylolpropane triacrylate (TMPTA). The materials were found to have an average pore diameter of 30–63 μm and a porosity of 77% and above. PEGDA crosslinked materials at 80 and 85% porosity, when swollen in PBS at 37 °C, were found to have an elastic modulus of 18 and 9.0 kPa respectively. PEGDA crosslinked materials were also found to have a swelling ratio of 700% in PBS at 37 °C. PEGDA crosslinked materials had improved visible light transmission properties when compared to TMPTA crosslinked materials under a bright field microscope. All materials were shown via hematoxylin and eosin staining to support the infiltration and attachment of induced pluripotent stem cell (iPSC)-derived human neural progenitor cells (hNPCs). HNPCs on all materials were demonstrated in short term 3D cultures to maintain a phenotype consistent with early neural lineage specification via immunohistochemical staining for the intermediate filament protein vimentin

Impact of ‘DEALTS2’ education intervention on trainer dementia knowledge and confidence to utilise innovative training approaches: A national pre-test – post-test survey

Background Gaps in acute care staff knowledge, skills, and attitudes towards dementia exist. Innovative training approaches that improve the delivery of care for people with dementia are needed. We were commissioned by Health Education England to develop and evaluate a new dementia education intervention ‘Dementia Education And Learning Through Simulation 2’ (DEALTS2), a simulation toolkit to enhance delivery of dementia training nationally across England. Objectives Evaluate differences in trainer dementia knowledge scores pre and post training, satisfaction with DEALTS2 Train-The-Trainer (TTT) workshops and simulation toolkit, confidence to use training approaches, and spread of implementation. Design A questionnaire survey using a pre-test – post-test design with measures completed: before (pre-test); after (T1); and 12 months post training (T2). Setting Twelve one-day DEALTS2 TTT workshops delivered across England in 2017. Participants National Health Service Trust staff employed in dementia training roles (n=199 trainers). Methods Trainers attended DEALTS2 TTT workshops and received the simulation toolkit. Data were collected between 2017 and 2018 using a questionnaire capturing differences in dementia knowledge scores, Likert scales and closed-ended questions measured satisfaction, confidence and implementation. Data were analysed using quantitative methods. Results Response rate was 92% (n=183) at pre-test/T1 and 26% (n=51) at T2. Trainer dementia knowledge scores increased from pre-test to T1 (p < 0.001) and were retained after 12 months in 5 of the 6 areas measured (pre-test to T2, p < 0.002); largest gains in ‘humanised approaches to dementia care’. 96% (n=176/183) were satisfied with DEALTS2 TTT workshops and simulation toolkit; 66.7% (n=34/51) felt confident to deliver dementia training informed by DEALTS2. Adherence rates were good with 45% (n=23/51) using the innovative training approaches within twelve months. Conclusions The results show DEALTS2 effectively increased trainer dementia knowledge and confidence to utilise innovative dementia training approaches. Implementation of DEALTS2 varied across organisations, therefore further research should explore factors determining successful implementation

The ANU WiFeS SuperNovA Program (AWSNAP)

This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Program (AWSNAP). AWSNAP is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph (WiFeS) on the Australian National University (ANU) 2.3m telescope. The first and primary data release of this program (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from July 2012 to August 2015. These spectra have been made publicly available via the WISeREP supernova spectroscopy repository. We analyse the AWSNAP sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the WiFeS instrument. In some cases we were able to use the integral-field nature of the WiFeS instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its "super-Chandrasekhar" status and enables measurement of the sub-solar host metallicity at the SN site.Comment: Submitted to Publications of the Astronomical Society of Australia (PASA). Spectra publicly released via WISeREP at http://wiserep.weizmann.ac.il

Relationships between affiliative social behavior and hair cortisol concentrations in semi-free ranging rhesus monkeys

Sociality is a fundamental aspect of human behavior and health. One benefit of affiliative social relationships is reduced short-term levels of glucocorticoids (GCs), which are indicative of physiological stress. Less is known, however, about chronic GC production in relation to affiliative social behavior. To address this issue, we studied a semi-free ranging troop of rhesus macaques (Macaca mulatta) and collected hair samples to measure hair cortisol concentrations (HCCs), as a measure of chronic GC production, during routine biannual exams. We collected social behavior (both aggressive and affiliative) and hair samples for 32 adult female rhesus macaques over one year (Experiment 1). Our results indicated that adult females who initiated higher levels of social affiliation had significantly lower levels of HCCs. Neither the initiation nor the receipt of aggression were significantly related to HCCs in this study. In a second experiment we studied 28 mother-infant dyads for the first 90 days postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We analyzed HCCs during weaning approximately one year later, which is a major transitional period. We found that infants that engaged in higher levels of mutual gazing in the first 90 days postpartum had significantly lower levels of HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to examine whether social behavior (such as play) in the first five months of life correlated with infant HCCs over those months (Experiment 3). We found that infant males that engaged in more social play had significantly lower levels of HCCs. By relying on an animal model, our study shows that affiliative social traits are associated with lower long-term GC production. Future research should address the complex interactions between social behavior, chronic GC production, and mental and physical health

Cognitive dysfunction after analgesia and sedation: Out of the operating room and into the pediatric intensive care unit

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately reverse translate critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care

A nonhuman primate model of inherited retinal disease.

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general