Discharge Identity of Medullary Inspiratory Neurons is Altered during Repetitive Fictive Cough

This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing

Semiclassical Theory of Coulomb Blockade Peak Heights in Chaotic Quantum Dots

We develop a semiclassical theory of Coulomb blockade peak heights in chaotic quantum dots. Using Berry's conjecture, we calculate the peak height distributions and the correlation functions. We demonstrate that the corrections to the corresponding results of the standard statistical theory are non-universal and can be expressed in terms of the classical periodic orbits of the dot that are well coupled to the leads. The main effect is an oscillatory dependence of the peak heights on any parameter which is varied; it is substantial for both symmetric and asymmetric lead placement. Surprisingly, these dynamical effects do not influence the full distribution of peak heights, but are clearly seen in the correlation function or power spectrum. For non-zero temperature, the correlation function obtained theoretically is in good agreement with that measured experimentally.Comment: 5 color eps figure

Interactive molecular dynamics in virtual reality from quantum chemistry to drug binding: An open-source multi-person framework

© 2019 Author(s). As molecular scientists have made progress in their ability to engineer nanoscale molecular structure, we face new challenges in our ability to engineer molecular dynamics (MD) and flexibility. Dynamics at the molecular scale differs from the familiar mechanics of everyday objects because it involves a complicated, highly correlated, and three-dimensional many-body dynamical choreography which is often nonintuitive even for highly trained researchers. We recently described how interactive molecular dynamics in virtual reality (iMD-VR) can help to meet this challenge, enabling researchers to manipulate real-time MD simulations of flexible structures in 3D. In this article, we outline various efforts to extend immersive technologies to the molecular sciences, and we introduce "Narupa," a flexible, open-source, multiperson iMD-VR software framework which enables groups of researchers to simultaneously cohabit real-time simulation environments to interactively visualize and manipulate the dynamics of molecular structures with atomic-level precision. We outline several application domains where iMD-VR is facilitating research, communication, and creative approaches within the molecular sciences, including training machines to learn potential energy functions, biomolecular conformational sampling, protein-ligand binding, reaction discovery using "on-the-fly" quantum chemistry, and transport dynamics in materials. We touch on iMD-VR's various cognitive and perceptual affordances and outline how these provide research insight for molecular systems. By synergistically combining human spatial reasoning and design insight with computational automation, technologies such as iMD-VR have the potential to improve our ability to understand, engineer, and communicate microscopic dynamical behavior, offering the potential to usher in a new paradigm for engineering molecules and nano-architectures

The effectiveness of e-Learning on biosecurity practice to slow the spread of invasive alien species

Online e-Learning is increasingly being used to provide environmental training. Prevention measures including biosecurity are essential to reducing the introduction and spread of invasive alien species (IAS) and are central to international and national IAS policy. This paper is the first to evaluate the effectiveness of e-Learning as a tool to increase awareness, risk perception and biosecurity behaviour in relation to IAS among individuals conducting work activities or research (fieldwork) in the field. We surveyed participants (a mixture of students and professionals) before, and 6 months after undertaking an e-Learning course on IAS and biosecurity practices. Awareness of IAS and self-reported biosecurity behaviour increased after e-Learning among students and professionals. Students had a lower awareness of IAS than professionals before training (20% of students vs 60% of professionals), but after training students showed a greater increase in awareness which led to similar levels of awareness post-training (81%). Prior to training, risk perception was also lower amongst students than professionals (33% of students and 59% of professionals were aware of the risk that their activities posed to the accidental spread of IAS). There was no change in risk perception amongst professionals after training, however training led to a doubling of risk perception in students. E-Learning also led to an increase in reported biosecurity behaviour and cleaning practices and there were higher levels of biosecurity cleaning amongst professionals. The higher awareness and better biosecurity amongst professionals is likely to reflect their familiarity with the issues of IAS and day-to-day activities in the field. Our results suggest that e-Learning is an effective tool to raise awareness and encourage behaviour change among field workers and researchers in an attempt to reduce the risk of accidental introduction and spread of IAS

Pandemic intake questionnaire to improve quality, effectiveness, and efficiency of outpatient neurologic and developmental care at the Kennedy Krieger institute during the COVID-19 pandemic

BackgroundThe COVID-19 pandemic uniquely affects patients with neurologic and developmental disabilities at the Kennedy Krieger Institute. These patients are at increased risk of co-morbidities, increasing their risk of contracting COVID-19. Disruptions in their home and school routines, and restrictions accessing crucial healthcare services has had a significant impact.MethodsA Pandemic Intake questionnaire regarding COVID-19 related medical concerns of guardians of patients was distributed using Qualtrics. Data from May-December 2020 were merged with demographic information of patients from 10 clinics (Center for Autism and Related Disorders (CARD), Neurology, Epigenetics, Neurogenetics, Center for Development and Learning (CDL) Sickle Cell, Spinal Cord, Sturge-Weber syndrome (SWS), Tourette's, and Metabolism). A provider feedback survey was distributed to program directors to assess the effectiveness of this intervention.ResultsAnalysis included responses from 1643 guardians of pediatric patients (mean age 9.5 years, range 0–21.6 years). Guardians of patients in more medically complicated clinics reported perceived increased risk of COVID-19 (p < 0.001) and inability to obtain therapies (p < 0.001) and surgeries (p < 0.001). Guardian responses from CARD had increased reports of worsening behavior (p = 0.01). Providers increased availability of in-person and virtual therapies and visits and made referrals for additional care to address this. In a survey of medical providers, five out of six program directors who received the responses to this survey found this questionnaire helpful in caring for their patients.ConclusionThis quality improvement project successfully implemented a pre-visit questionnaire to quickly assess areas of impact of COVID-19 on patients with neurodevelopmental disorders. During the pandemic, results identified several major areas of impact, including patient populations at increased risk for behavioral changes, sleep and/or disruptions of medical care. Most program directors reported improved patient care as a result

Exploring knowledge, perception of risk and biosecurity practices among researchers in the UK: a quantitative survey

Accidental introduction and/or spread of Invasive Non-Native Species (INNS) can result from a range of activities including agriculture, transport, trade and recreation. Researchers represent an important group of stakeholders who undertake activities in the field that could potentially facilitate the spread of INNS. Biosecurity is key to preventing the introduction and spread of INNS. Risk perceptions are a fundamental component in determining behaviour, so understanding how researchers perceive the risks associated with their activities can help us understand some of the drivers of biosecurity behaviour in the field. The aim of this study was to investigate researchers’ perceptions of risk in relation to their field activities and whether risk perceptions influenced behaviour. We gathered quantitative data on perceptions of risk and biosecurity practices using an online questionnaire. Only 35% of all respondents considered their field activities to pose some risk in terms of spreading INNS. Higher risk perception was found in those who undertook high risk activities or where INNS were known/expected to be present. However, whilst respondents with experience of INNS were more likely to report consciously employing biosecurity in the field, this did not translate into better actual biosecurity practices. Awareness of biosecurity campaigns did in fact increase perception of risk, perceived and actual biosecurity behaviour. However, there remains a disconnect between reported and actual biosecurity practices, including a lack of understanding about what constitutes good biosecurity practice. These findings should be used to improve targeted awareness raising campaigns and help create directed training on biosecurity practices

Landscape history, time lags and drivers of change : urban natural grassland remnants in Potchefstroom, South Africa

The history of the landscape directly affects biotic assemblages, resulting in time lags in species response to disturbances. In highly fragmented environments, this phenomenon often causes extinction debts. However, few studies have been carried out in urban settings. To determine if there are time lags in the response of temperate natural grasslands to urbanization. Does it differ for indigenous species and for species indicative of disturbance and between woody and open grasslands? Do these time lags change over time? What are the potential landscape factors driving these changes? What are the corresponding vegetation changes? In 1995 and 2012 vegetation sampling was carried out in 43 urban grassland sites. We calculated six urbanization and landscape measures in a 500 m buffer area surrounding each site for 1938, 1961, 1970, 1994, 1999, 2006, and 2010. We used generalized linear models and model selection to determine which time period best predicted the contemporary species richness patterns. Woody grasslands showed time lags of 20-40 years. Contemporary open grassland communities were, generally, associated with more contemporary landscapes. Altitude and road network density of natural areas were the most frequent predictors of species richness. The importance of the predictors changed between the different models. Species richness, specifically, indigenous herbaceous species, declined from 1995 to 2012. The history of urbanization affects contemporary urban vegetation assemblages. This indicates potential extinction debts, which have important consequences for biodiversity conservation planning and sustainable future scenarios.Peer reviewe

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya

IntroductionGlobally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies.MethodsHealthy women ages 18–34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition.ResultsAmong 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36–90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and −27.1% to −20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively).ConclusionTFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR.Clinical Trial RegistrationNCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance