Building for the future: essential infrastructure for rodent ageing studies

When planning ageing research using rodent models, the logistics of supply, long term housing and infrastructure provision are important factors to take into consideration. These issues need to be prioritised to ensure they meet the requirements of experiments which potentially will not be completed for several years. Although these issues are not unique to this discipline, the longevity of experiments and indeed the animals, requires a high level of consistency and sustainability to be maintained throughout lengthy periods of time. Moreover, the need to access aged stock or material for more immediate experiments poses many issues for the completion of pilot studies and/or short term intervention studies on older models. In this article, we highlight the increasing demand for ageing research, the resources and infrastructure involved, and the need for large-scale collaborative programmes to advance studies in both a timely and a cost-effective way

The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study: protocol for an international multicentre randomised controlled trial

Introduction: Postoperative delirium is one of the most common complications of major surgery, affecting 10–70% of surgical patients 60 years and older. Delirium is an acute change in cognition that manifests as poor attention and illogical thinking and is associated with longer intensive care unit (ICU) and hospital stay, long-lasting cognitive deterioration and increased mortality. Ketamine has been used as an anaesthetic drug for over 50 years and has an established safety record. Recent research suggests that, in addition to preventing acute postoperative pain, a subanaesthetic dose of intraoperative ketamine could decrease the incidence of postoperative delirium as well as other neurological and psychiatric outcomes. However, these proposed benefits of ketamine have not been tested in a large clinical trial. Methods: The Prevention of Delirium and Complications Associated with Surgical Treatments (PODCAST) study is an international, multicentre, randomised controlled trial. 600 cardiac and major non-cardiac surgery patients will be randomised to receive ketamine (0.5 or 1 mg/kg) or placebo following anaesthetic induction and prior to surgical incision. For the primary outcome, blinded observers will assess delirium on the day of surgery (postoperative day 0) and twice daily from postoperative days 1–3 using the Confusion Assessment Method or the Confusion Assessment Method for the ICU. For the secondary outcomes, blinded observers will estimate pain using the Behavioral Pain Scale or the Behavioral Pain Scale for Non-Intubated Patients and patient self-report. Ethics and dissemination The PODCAST trial has been approved by the ethics boards of five participating institutions; approval is ongoing at other sites. Recruitment began in February 2014 and will continue until the end of 2016. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement and popular media. Registration details The study is registered at clinicaltrials.gov, NCT01690988 (last updated March 2014). The PODCAST trial is being conducted under the auspices of the Neurological Outcomes Network for Surgery (NEURONS). Trial registration number NCT01690988 (last updated December 2013)

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (2.5 hour). ETHICS AND DISSEMINATION Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER CRD42018090261

Determining solar effects in Neptune’s atmosphere

Long-duration observations of Neptune’s brightness in two visible wavelengths provide a disk-averaged estimate of its atmospheric aerosol. Brightness variations were previously associated with the 11-year solar cycle, through solar-modulated mechanisms linked with either ultra-violet (UV) or galactic cosmic ray (GCR) effects on atmospheric particles. Here we use a recently extended brightness dataset (1972-2014), with physically realistic modelling to show that rather than alternatives, UV and GCR are likely to be modulating Neptune’s atmosphere in combination. The importance of GCR is further supported by the response of Neptune's atmosphere to an intermittent 1.5 to 1.9 year periodicity, which occurred preferentially in GCR (not UV) during the mid-1980s. This periodicity was detected both at Earth, and in GCR measured by Voyager 2, then near Neptune. A similar coincident variability in Neptune’s brightness suggests nucleation onto GCR ions. Both GCR and UV mechanisms may occur more rapidly than the subsequent atmospheric particle transport

Global response of the upper thermospheric winds to large ion drifts in the Jovian ovals

We use our fully coupled 3‐D Jupiter Thermosphere General Circulation Model (JTGCM) to quantify processes which are responsible for generating neutral winds in Jupiter’s oval thermosphere from 20 µbar to 10−4 nbar self‐consistently with the thermal structure and composition. The heat sources in the JTGCM that drive the global circulation of neutral flow are substantial Joule heating produced in the Jovian ovals by imposing high‐speed anticorotational ion drifts (~3.5 km s−1) and charged particle heating from auroral processes responsible for bright oval emissions. We find that the zonal flow of neutral winds in the auroral ovals of both hemispheres is primarily driven by competition between accelerations resulting from Coriolis forcing and ion drag processes near the ionospheric peak. However, above the ionospheric peak (<0.01 µbar), the acceleration of neutral flow due to pressure gradients is found to be the most effective parameter impacting zonal winds, competing mainly with acceleration due to advection with minor contributions from curvature and Coriolis forces in the southern oval, while in the northern oval it competes alone with considerable Coriolis forcing. The meridional flow of neutral winds in both ovals in the JTGCM is determined by competition between meridional accelerations due to Coriolis forcing and pressure gradients. We find that meridional flow in the lower thermosphere, near the peak of the auroral ionosphere, is poleward, with peak wind speeds of ~0.6 km s−1 and ~0.1 km s−1 in the southern and northern oval, respectively. The corresponding subsiding flow of neutral motion is ~5 m s−1 in the southern oval, while this flow is rising in the northern oval with reduced speed of ~2 m s−1. We also find that the strength of meridional flow in both auroral ovals is gradually weakened and turned equatorward near 0.08 µbar with wind speeds up to ~250 m s−1 (southern oval) and ~75 m s−1 (northern oval). The corresponding neutral motion in this region is upward, with wind speeds up to 4 m s−1 in both ovals.Key PointsUnderlying thermal and dynamical processes of the Jovian thermosphereForcing terms responsible for generating Jupiter’s neutral wind speedsSimulated neutral wind speed is compared with the measured wind speedPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146281/1/jgra52522_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146281/2/jgra52522.pd

Spin dynamics in semiconductors

This article reviews the current status of spin dynamics in semiconductors which has achieved a lot of progress in the past years due to the fast growing field of semiconductor spintronics. The primary focus is the theoretical and experimental developments of spin relaxation and dephasing in both spin precession in time domain and spin diffusion and transport in spacial domain. A fully microscopic many-body investigation on spin dynamics based on the kinetic spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published in Physics Reports

Molecular Mechanism of Insulin Resistance in Obesity and Type 2 Diabetes

Insulin resistance is a major risk factor for developing type 2 diabetes caused by the inability of insulin-target tissues to respond properly to insulin, and contributes to the morbidity of obesity. Insulin action involves a series of signaling cascades initiated by insulin binding to its receptor, eliciting receptor autophosphorylation and activation of the receptor tyrosine kinase, resulting in tyrosine phosphorylation of insulin receptor substrates (IRSs). Phosphorylation of IRSs leads to activation of phosphatidylinositol 3-kinase (PI3K) and, subsequently, to activation of Akt and its downstream mediator AS160, all of which are important steps for stimulating glucose transport induced by insulin. Although the mechanisms underlying insulin resistance are not completely understood in skeletal muscle, it is thought to result, at least in part, from impaired insulin-dependent PI3K activation and downstream signaling. This review focuses on the molecular basis of skeletal muscle insulin resistance in obesity and type 2 diabetes. In addition, the effects of insulin-sensitizing agent treatment and lifestyle intervention of human insulin-resistant subjects on insulin signaling cascade are discussed. Furthermore, the role of Rho-kinase, a newly identified regulator of insulin action in insulin control of metabolism, is addressed

Connected consciousness after tracheal intubation in young adults: an international multicentre cohort study

Background: Connected consciousness, assessed by response to command, occurs in at least 5% of general anaesthetic procedures and perhaps more often in young people. Our primary objective was to establish the incidence of connected consciousness after tracheal intubation in young people aged 18e40 yr. The secondary objectives were to assess the nature of these responses, identify relevant risk factors, and determine their relationship to postoperative outcomes. Methods: This was an international, multicentre prospective cohort study using the isolated forearm technique to assess connected consciousness shortly after tracheal intubation. Results: Of 344 enrolled subjects, 338 completed the study (mean age, 30 [standard deviation, 6.3] yr; 232 [69%] female). Responses after intubation occurred in 37/338 subjects (11%). Females (13%, 31/232) responded more often than males (6%, 6/106). In logistic regression, the risk of responsiveness was increased with female sex (odds ratio [OR adjusted ]¼2.7; 95% confidence interval [CI], 1.1e7.6; P¼0.022) and was decreased with continuous anaesthesia before laryngoscopy (OR adjusted ¼0.43; 95% CI, 0.20e0.96; P¼0.041). Responses were more likely to occur after a command to respond (and not to nonsense, 13 subjects) than after a nonsense statement (and not to command, four subjects, P¼0.049). Conclusions: Connected consciousness occured after intubation in 11% of young adults, with females at increased risk. Continuous exposure to anaesthesia between induction of anaesthesia and tracheal intubation should be considered t

Semiconductor Superlattices: A model system for nonlinear transport

Electric transport in semiconductor superlattices is dominated by pronounced negative differential conductivity. In this report the standard transport theories for superlattices, i.e. miniband conduction, Wannier-Stark-hopping, and sequential tunneling, are reviewed in detail. Their relation to each other is clarified by a comparison with a quantum transport model based on nonequilibrium Green functions. It is demonstrated how the occurrence of negative differential conductivity causes inhomogeneous electric field distributions, yielding either a characteristic sawtooth shape of the current-voltage characteristic or self-sustained current oscillations. An additional ac-voltage in the THz range is included in the theory as well. The results display absolute negative conductance, photon-assisted tunneling, the possibility of gain, and a negative tunneling capacitance.Comment: 121 pages, figures included, to appear in Physics Reports (2001