High frequency transient-evoked otoacoustic emission measurements using chirp and click stimuli.

Transient-evoked otoacoustic emissions (TEOAEs) at high frequencies are a non-invasive physiological test of basilar membrane mechanics at the basal end, and have clinical potential to detect risk of hearing loss related to outer-hair-cell dysfunction. Using stimuli with constant incident pressure across frequency, TEOAEs were measured in experiment 1 at low frequencies (0.7-8 kHz) and high frequencies (7.

Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR.

Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) that are functionally brighter; detect submicromolar to millimolar amounts of glutamate; and have blue, cyan, green, or yellow emission profiles. These variants could be imaged in vivo in cases where original iGluSnFR was too dim, resolved glutamate transients in dendritic spines and axonal boutons, and allowed imaging at kilohertz rates.

Structuring Diabetes Mellitus Care in Long-Term Nursing Home Residents.

Nursing home residents with diabetes have more complex care needs with higher levels of comorbidity, disability and cognitive impairment. We compared current practice in the 44 long-term residents in Peamount hospital with the standards recommended in the Diabetes UK "Good Clinical Practice Guidelines for Care Home Residents with Diabetes". Of 44 residents, 11 were diabetic.

Distributed network interactions and their emergence in developing neocortex.

The principles governing the functional organization and development of long-range network interactions in the neocortex remain poorly understood. Using in vivo widefield and two-photon calcium imaging of spontaneous activity patterns in mature ferret visual cortex, we find widespread modular correlation patterns that accurately predict the local structure of visually evoked orientation columns several millimeters away. Longitudinal imaging demonstrates that long-range spontaneous correlations are present early in cortical development before the elaboration of horizontal connections and predict mature network structure.

Evaluation of a device to improve non-coring needle insertion into implanted intravenous ports.

Implanted intravenous ports (IPs) are increasingly used in health care. The experience of having IPs accessed can vary a great deal for patients. Successful IP access depends on the experience and skill of the health professional and wrongly positioned attempts are not only painful for the patient but can also cause damage to the outer casing of the IP.

Intracochlear Electrocochleography: Response Patterns During Cochlear Implantation and Hearing Preservation.

Objectives: Electrocochleography (ECochG) obtained through a cochlear implant (CI) is increasingly being tested as an intraoperative monitor during implantation with the goal of reducing surgical trauma. Reducing trauma should aid in preserving residual hearing and improve speech perception overall. The purpose of this study was to characterize intracochlear ECochG responses throughout insertion in a range of array types and, when applicable, relate these measures to hearing preservation.

Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials.

Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan). Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.

Across-the-World Automated Optimization and Continuous-Flow Synthesis of Pharmaceutical Agents Operating Through a Cloud-Based Server.

The power of the Cloud has been harnessed for pharmaceutical compound production with remote servers based in Tokyo, Japan being left to autonomously find optimal synthesis conditions for three active pharmaceutical ingredients (APIs) in laboratories in Cambridge, UK. A researcher located in Los Angeles, USA controlled the entire process via an internet connection. The constituent synthetic steps for Tramadol, Lidocaine, and Bupropion were thus optimized with minimal intervention from operators within hours, yielding conditions satisfying customizable evaluation functions for all examples.

Common genetic variants contribute to risk of rare severe neurodevelopmental disorders.

There are thousands of rare human disorders that are caused by single deleterious, protein-coding genetic variants. However, patients with the same genetic defect can have different clinical presentations, and some individuals who carry known disease-causing variants can appear unaffected. Here, to understand what explains these differences, we study a cohort of 6,987 children assessed by clinical geneticists to have severe neurodevelopmental disorders such as global developmental delay and autism, often in combination with abnormalities of other organ systems.

The genetic architecture of aniridia and Gillespie syndrome.

Absence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygous PAX6 loss-of-function mutations.

Oxygen exposures at NASA's Neutral Buoyancy Lab: a 20-year experience.

Astronauts training for extravehicular activity (EVA) operations can spend many hours submerged underwater in a pressurized suit, called an extravehicular mobility unit (EMU), exposed to pressures exceeding 2 atmospheres absolute (ATA). To minimize the risk of decompression sickness (DCS) a 46% nitrox mixture is used. This limits the nitrogen partial pressure, decreasing the risk of DCS.

The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in adaptation during cystic fibrosis infection.

Chronic infection with opportunistic pathogens including Burkholderia cepacia complex (Bcc) is a hallmark of cystic fibrosis (CF). We investigated the adaptive mechanisms facilitating chronic lung infection in sequential Bcc isolates from two siblings with CF (P1 and P2), one of whom also experienced intermittent blood-stream infections (P2). We previously showed increased lung cell attachment with colonisation time in both P1 and P2.

Residual Cochlear Function in Adults and Children Receiving Cochlear Implants: Correlations With Speech Perception Outcomes.

Objectives: Variability in speech perception outcomes with cochlear implants remains largely unexplained. Recently, electrocochleography, or measurements of cochlear potentials in response to sound, has been used to assess residual cochlear function at the time of implantation. Our objective was to characterize the potentials recorded preimplantation in subjects of all ages, and evaluate the relationship between the responses, including a subjective estimate of neural activity, and speech perception outcomes.

Comparison of Stroke Outcomes of Hub and Spoke Hospital Treated Patients in Mayo Clinic Telestroke Program.

Purpose: To examine telemedicine as it applies to acute ischemic stroke care at a spoke hospital and the effect on patient outcomes, including the timeliness of response, quality of care, safety, morbidity, and mortality when compared to standard hub hospital stroke center care.

Methods: Retrospective review of prospectively entered quality/performance stroke/telestroke patient catalog data were completed for 1000 adult patients who presented with an acute ischemic stroke to the Mayo Clinic Hospitals (500 patients) or to one of thirteen Mayo Clinic affiliated telestroke spoke hospitals in the regions (500 patients). The primary outcome of interest was the percentage of accurate decision making for eligibility of IV alteplase administration assessed by blinded adjudication and the secondary outcomes pertained to complications, discharge parameters, and standard quality metrics.

Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2.

A variety of innate immune responses and functions are dependent on time of day, and many inflammatory conditions are associated with dysfunctional molecular clocks within immune cells. However, the functional importance of these innate immune clocks has yet to be fully characterized. NRF2 plays a critical role in the innate immune system, limiting inflammation via reactive oxygen species (ROS) suppression and direct repression of the proinflammatory cytokines, IL-1β and IL-6.

Differential tuning of excitation and inhibition shapes direction selectivity in ferret visual cortex.

To encode specific sensory inputs, cortical neurons must generate selective responses for distinct stimulus features. In principle, a variety of factors can contribute to the response selectivity of a cortical neuron: the tuning and strength of excitatory and inhibitory synaptic inputs, dendritic nonlinearities and spike threshold. Here we use a combination of techniques including in vivo whole-cell recording, synaptic- and cellular-resolution in vivo two-photon calcium imaging, and GABA (γ-aminobutyric acid) neuron-selective optogenetic manipulation to dissect the factors that contribute to the direction-selective responses of layer 2/3 neurons in ferret visual cortex (V1).

Stereotactic radiosurgery to surgical cavity post resection of brain metastases: Local recurrence and overall survival rates. A single-centre experience.

Introduction: We reviewed local control (LC) and overall survival (OS) post intracranial SRS to cavity post resection of brain metastases at one institution, and factors affecting LC.

Methods: A retrospective review was conducted of adjuvant SRS at one institution from 2013 to 2016. Patient records, treatment plans and diagnostic images were reviewed.

The effect of entomopathogenic fungal culture filtrate on the immune response and haemolymph proteome of the large pine weevil, Hylobius abietis.

The large pine weevil Hylobius abietis L. is a major forestry pest in 15 European countries, where it is a threat to 3.4 million hectares of forest.

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide.

Genome analysis of the yeast Diutina catenulata, a member of the Debaryomycetaceae/Metschnikowiaceae (CTG-Ser) clade.

Diutina catenulata (Candida catenulata) is an ascomycetous yeast that has been isolated from humans, animals and environmental sources. The species is a contaminant of dairy products, and has been linked to superficial and invasive infections in both humans and animals. Previous phylogenetic analyses have assigned the species to the Saccharomycetales, but failed to identify its specific clade.

The feasibility, acceptability and preliminary testing of a novel, low-tech intervention to improve pre-hospital data recording for pre-alert and handover to the Emergency Department.

Background: Poor communication during patient handover is recognised internationally as a root cause of a significant proportion of preventable deaths. Data used in handover is not always easily recorded using ambulance based tablets, particularly in time-critical cases. Paramedics have therefore developed pragmatic workarounds (writing on gloves or scrap paper) to record these data.

Paramedic determination of appropriate emergency department destination.

Background: Freestanding emergency departments (FSED) are equipped to care for most emergencies, but do not have all the resources that hospital-based emergency departments (ED) offer. As the number of FSEDs grows rapidly, emergency medical services (EMS) must routinely determine whether a FSED is an appropriate destination. Inappropriate triage may delay definitive care, potentially increasing morbidity, mortality, and resource utilization.

Magnetic Resonance Imaging Evaluation of the Distal Biceps Tendon.

Injuries to the distal biceps occur at the tendinous insertion at the radial tuberosity. Distal biceps injuries range from tendinosis to partial tears to non-retracted and retracted complete tears. Acute and chronic complete tears result from a tendinous avulsion at the radial tuberosity.

Critcomms: a national cross-sectional questionnaire based study to investigate prehospital handover practices between ambulance clinicians and specialist prehospital teams in Scotland.

Background: Poor communication during patient handover is recognised internationally as a root cause of a significant proportion of preventable deaths. Improving the accuracy and quality of handover may reduce associated mortality and morbidity. Although the practice of handover between Ambulance and Emergency Department clinicians has received some attention over recent years there is little evidence to support handover best practice within the prehospital domain.