Plasma pTau217 ratio predicts continuous regional brain tau accumulation in amyloid-positive early Alzheimer's disease.

Background: This study examines whether phosphorylated plasma Tau217 ratio (pTau217R) can predict tau accumulation in different brain regions, as measured by positron emission tomography (PET) standardized uptake value ratio (SUVR), for staging Alzheimer's disease (AD).

Methods: Plasma pTau217R was measured using immunoprecipitation-mass spectrometry. Models for predicting tau PET SUVR, developed with 144 early AD individuals using [F]MK6240, were validated in two validation sets, VS1 (98 early AD) and VS2 (47 preclinical/early AD with a different tracer, flortaucipir (Tauvid)), all amyloid-beta positive (Aβ+).

Modelling plausible scenarios for the Omicron SARS-CoV-2 variant from early-stage surveillance.

We used a spatially explicit agent-based model of SARS-CoV-2 transmission combined with spatially fine-grained COVID-19 observation data from Public Health Scotland to investigate the initial rise of the Omicron (BA.1) variant of concern. We evaluated plausible scenarios for transmission rate advantage and vaccine immune escape relative to the Delta variant based on the data that would have been available at that time.

Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease.

Background: This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.

Methods: Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation-mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts.

Artificial intelligence for dementia drug discovery and trials optimization.

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress.

Multi-resonant open-access microcavity arrays for light matter interaction.

We report the realisation of a high-finesse open-access cavity array, tailored towards the creation of multiple coherent light-matter interfaces within a compact environment. We describe the key technical developments put in place to fabricate such a system, comprising the creation of tapered pyramidal substrates and an in-house laser machining setup. Cavities made from these mirrors are characterised, by laser spectroscopy, to possess similar optical properties to state-of-the-art fibre-tip cavities, but offer a compelling route towards improved performance, even when used to support only a single mode.

SCoVMod - a spatially explicit mobility and deprivation adjusted model of first wave COVID-19 transmission dynamics.

: Mobility restrictions prevent the spread of infections to disease-free areas, and early in the coronavirus disease 2019 (COVID-19) pandemic, most countries imposed severe restrictions on mobility as soon as it was clear that containment of local outbreaks was insufficient to control spread. These restrictions have adverse impacts on the economy and other aspects of human health, and it is important to quantify their impact for evaluating their future value. : Here we develop Scotland Coronavirus transmission Model (SCoVMod), a model for COVID-19 in Scotland, which presents unusual challenges because of its diverse geography and population conditions.

Increasing the Cognitive Screening Efficiency of Global Phase III Trials in Early Alzheimer Disease: The Cognitive Task Force.

Purpose: A Cognitive Task Force (CTF) was established for the MissionAD program with the aim of reducing the screen failure (SF) rate to ∼30% and thereby reduce unnecessary subject burden, site burden, and excess trial costs.

Methods/subjects: The MissionAD program consisted of 2 global phase 3 studies evaluating the BACE inhibitor elenbecestat in subjects with early Alzheimer disease. The CTF monitored and engaged with MissionAD clinical sites to provide support through collegial discussions to maximize the efficiency of the preconsent recruitment phase.

Dexmedetomidine prolongs the duration of action of mepivacaine on anesthesia of the palmar digital nerves of horses.

Objective: To determine whether palmar digital nerve (PDN) blockade in horses with a combination of dexmedetomidine and mepivacaine would block the response to mechanical force applied to the digit longer than would anesthetizing these nerves with mepivacaine alone or dexmedetomidine alone.

Animals: 8 mares with no signs of lameness.

Procedures: In a randomized, crossover, blinded, experimental study, both PDNs of the same forelimb of each horse were anesthetized by perineural injection with either 30 mg mepivacaine alone, 250 µg of dexmedetomidine alone, or 30 mg mepivacaine combined with 250 µg of dexmedetomidine.

Influence of a novel scaffold composed of polyurethane, hydroxyapatite, and decellularized bone particles on the healing of fourth metacarpal defects in mares.

Objective: To determine the effect of a novel scaffold, designed for use in bone regeneration, on healing of splint bone segmental defects in mares.

Study Design: In vivo experimental study.

Sample Population: Five adult mares (4-10 years old; mean weight, 437.

Sedative effects and pharmacokinetics of detomidine when administered intravenously and intravaginally as a gel in alpacas.

Objectives: To evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine.

Study Design: Randomized, crossover, blinded experiment.

Animals: A group of six healthy adult female Huacaya alpacas (70.

Efficacy and duration of effect for liposomal bupivacaine when administered perineurally to the palmar digital nerves of horses.

Objective: To determine the efficacy and duration of effect for liposomal bupivacaine following perineural administration to the medial and lateral palmar digital nerves of horses.

Animals: 9 nonlame mares.

Procedures: For each horse, 2 mL of liposomal bupivacaine (13.

Evaluation of the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to horses.

Objectives: To determine the sedative effects and pharmacokinetic profile of detomidine when administered intravaginally as a gel formulation to horses.

Study Design: Randomized, crossover, masked experimental design.

Animals: A group of six healthy adult mares (494 ± 56 kg).

Effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone preventing movement in dogs.

Objective: To determine the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIR) in dogs.

Study Design: Experimental crossover design.

Animals: A group of six healthy, adult, intact female mixed-breed dogs, weighing 19.

Manipulation of contact network structure and the impact on foot-and-mouth disease transmission.

The movements of livestock between premises and markets can be characterised as a dynamic network where the structure of the network itself can critically impact the transmission dynamics of many infectious diseases. As evidenced by the 2001 foot-and-mouth disease (FMD) epidemic in the UK, this can involve transmission over large geographical distances and can result in major economic loss. One consequence of the FMD epidemic was the introduction of mandatory livestock movement restrictions: a 13-day standstill in Scotland for cattle and sheep after moving livestock onto a farm (allowing many exemptions) and a 6-day standstill for cattle and sheep in England and Wales (with minor exemptions, e.

Minimum alveolar concentration: Key concepts and a review of its pharmacological reduction in dogs. Part 2.

Objective: To outline the major components of the minimum alveolar concentration (MAC) and review the literature regarding pharmacological manipulation of the MAC of halothane, isoflurane, sevoflurane, enflurane, and desflurane in dogs. The pharmacological agents included are alpha-2 agonists, benzodiazepines, propofol, opioids, lidocaine, acepromazine, non-steroidal anti-inflammatory agents (NSAIDs), maropitant, and NMDA antagonists. Part 2 of this review will focus on the effect of opioids, lidocaine, NSAIDs, maropitant, acepromazine, and NMDA antagonists on MAC.

Minimum alveolar concentration: Key concepts and a review of its pharmacological reduction in dogs. Part 1.

Objective: To outline the major components of the minimum alveolar concentration (MAC) and review the literature in regard to pharmacological manipulation of the MAC of halothane, isoflurane, sevoflurane, enflurane, and desflurane in dogs. The pharmacologic agents included are alpha-2 agonists, benzodiazepines, propofol, maropitant, opioids, lidocaine, acepromazine, non-steroidal anti-inflammatory agents, and NMDA antagonists. Part 1 will focus on summarizing the relevance, measurement, and mechanisms of MAC and review the effects of alpha-2 agonists, benzodiazepines, and propofol on MAC.

Effects of stacked wedge pads and chains applied to the forefeet of Tennessee Walking Horses for a five-day period on behavioral and biochemical indicators of pain, stress, and inflammation.

OBJECTIVE To determine the effects of stacked wedge pads and chains applied to the forefeet of Tennessee Walking Horses on behavioral and biochemical indicators of pain, stress, and inflamation. ANIMALS 20 Tennessee Walking Horses. PROCEDURES Horses were randomly assigned to 2 treatment groups: keg shoes (control; n = 10) or stacked wedge pads and exercise with chains (10).

Dissipatively coupled waveguide networks for coherent diffusive photonics.

A photonic circuit is generally described as a structure in which light propagates by unitary exchange and transfers reversibly between channels. In contrast, the term 'diffusive' is more akin to a chaotic propagation in scattering media, where light is driven out of coherence towards a thermal mixture. Based on the dynamics of open quantum systems, the combination of these two opposites can result in novel techniques for coherent light control.

Effect of dexmedetomidine on the minimum infusion rate of propofol preventing movement in dogs.

Objective: To determine the effect of dexmedetomidine on induction dose and minimum infusion rate of propofol preventing movement (MIR).

Study Design: Randomized crossover, unmasked, experimental design.

Animals: Three male and three female healthy Beagle dogs weighing 10.

Assessment of agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scoring the recovery of horses from anesthesia by use of subjective grading scales and development of a system for evaluation of the recovery of horses from anesthesia by use of accelerometry.

OBJECTIVE To evaluate agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scores determined by use of a simple descriptive scale (SDS) or a composite grading scale (CGS) for quality of recovery of horses from anesthesia and to investigate use of 3-axis accelerometry (3AA) for objective evaluation of recovery. ANIMALS 12 healthy adult horses. PROCEDURES Horses were fitted with a 3AA device and then were anesthetized.

Pharmacokinetics and pharmacodynamics of midazolam following intravenous and intramuscular administration to sheep.

OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep. ANIMALS 8 healthy adult rams. PROCEDURES Sheep were administered midazolam (0.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MAC) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals).

Effect of dexmedetomidine hydrochloride on tiletamine hydrochloride-zolazepam hydrochloride anesthesia in alpacas.

OBJECTIVE To evaluate the effect of IM administration of a tiletamine hydrochloride-zolazepam hydrochloride (TZ) combination with either dexmedetomidine hydrochloride or saline (0.9% NaCl) solution (SS) on the motor response to claw clamping, selected cardiorespiratory variables, and quality of recovery from anesthesia in alpacas. ANIMALS 5 adult sexually intact male alpacas.

Field Sedation and Anesthesia of Ruminants.

Many surgical procedures on ruminants can be performed humanely and safely using local or regional anesthesia and physical restraint, but sedation and general anesthesia are necessary in order to perform some procedures. Although anesthesia-associated risks are greater in ruminants than monogastrics, ruminants can be anesthetized relatively safely in a field setting if the risks are understood, and adequate planning and precautions are in place. This article discusses the important features impacting sedation and anesthesia of cattle and small ruminants, and describes some commonly used drug protocols.