What can a mean-field model tell us about the dynamics of the cortex?

In this chapter we examine the dynamical behavior of a spatially homogeneous two-dimensional model of the cortex that incorporates membrane potential, synaptic flux rates and long- and short-range synaptic input, in two spatial dimensions, using parameter sets broadly realistic of humans and rats. When synaptic dynamics are included, the steady states may not be stable. The bifurcation structure for the spatially symmetric case is explored, identifying the positions of saddle–node and sub- and supercritical Hopf instabilities. We go beyond consideration of small-amplitude perturbations to look at nonlinear dynamics. Spatially-symmetric (breathing mode) limit cycles are described, as well as the response to spatially-localized impulses. When close to Hopf and saddle–node bifurcations, such impulses can cause traveling waves with similarities to the slow oscillation of slow-wave sleep. Spiral waves can also be induced. We compare model dynamics with the known behavior of the cortex during natural and anesthetic-induced sleep, commenting on the physiological significance of the limit cycles and impulse responses

Micromanipulation of InP lasers with optoelectronic tweezers for integration on a photonic platform

The integration of light sources on a photonic platform is a key aspect of the fabrication of self-contained photonic circuits with a small footprint that does not have a definitive solution yet. Several approaches are being actively researched for this purpose. In this work we propose optoelectronic tweezers for the manipulation and integration of light sources on a photonic platform and report the positional and angular accuracy of the micromanipulation of standard Fabry-Pérot InP semiconductor laser die. These lasers are over three orders of magnitude bigger in volume than any previously assembled with optofluidic techniques and the fact that they are industry standard lasers makes them significantly more useful than previously assembled microdisk lasers. We measure the accuracy to be 2.5 ± 1.4 µm and 1.4 ± 0.4° and conclude that optoelectronic tweezers are a promising technique for the micromanipulation and integration of optoelectronic components in general and semiconductor lasers in particular

Cryogenic mechanical loss of a single-crystalline GaP coating layer for precision measurement applications

The first direct observations of gravitational waves have been made by the Advanced LIGO detectors. However, the quest to improve the sensitivities of these detectors remains, and epitaxially grown single-crystal coatings show considerable promise as alternatives to the ion-beam sputtered amorphous mirror coatings typically used in these detectors and other such precision optical measurements. The mechanical loss of a 1 μm thick single-crystalline gallium phosphide (GaP) coating, incorporating a buffer layer region necessary for the growth of high quality epitaxial coatings, has been investigated over a broad range of frequencies and with fine temperature resolution. It is shown that at 20 K the mechanical loss of GaP is a factor of 40 less than an undoped tantala film heat-treated to 600 °C and is comparable to the loss of a multilayer GaP/AlGaP coating. This is shown to translate into possible reductions in coating thermal noise of a factor of 2 at 120 K and 5 at 20 K over the current best IBS coatings (alternating stacks of silica and titania-doped tantala). There is also evidence of a thermally activated dissipation process between 50 and 70 K

A Low Cost Technique for Adding Microlasers to a Silicon Photonic Platform

In this paper we report the physical micromanipulation of standard InP telecommunications laser die in a liquid medium by means of optoelectronic tweezers. Optoelectronic tweezers have been shown to use much less optical power than optical tweezers, they do not require a coherent light source to function and the creation of multiple traps is straightforward. These properties make the technique a very good candidate for the massive parallel micromanipulation of optoelectronic components for assembly on a photonic platform. We discuss the positional and orientation accuracy of the optoelectronic tweezers in relation to the alignment requirements for low-loss coupling between the light sources and the other components in a photonic platform. Our experiments indicate that the accuracy is better than 2 µm and 2◦ for translations and rotations, respectively

Combining Slaughterhouse Surveillance Data with Cattle Tracing Scheme and Environmental Data to Quantify Environmental Risk Factors for Liver Fluke in Cattle.

Liver fluke infection causes serious disease (fasciolosis) in cattle and sheep in many regions of the world, resulting in production losses and additional economic consequences due to condemnation of the liver at slaughter. Liver fluke depends on mud snails as an intermediate host and infect livestock when ingested through grazing. Therefore, environmental factors play important roles in infection risk and climate change is likely to modify this. Here, we demonstrate how slaughterhouse data can be integrated with other data, including animal movement and climate variables to identify environmental risk factors for liver fluke in cattle in Scotland. We fitted a generalized linear mixed model to the data, with exposure-weighted random and fixed effects, an approach which takes into account the amount of time cattle spent at different locations, exposed to different levels of risk. This enabled us to identify an increased risk of liver fluke with increased animal age, rainfall, and temperature and for farms located further to the West, in excess of the risk associated with a warmer, wetter climate. This model explained 45% of the variability in liver fluke between farms, suggesting that the unexplained 55% was due to factors not included in the model, such as differences in on-farm management and presence of wet habitats. This approach demonstrates the value of statistically integrating routinely recorded slaughterhouse data with other pre-existing data, creating a powerful approach to quantify disease risks in production animals. Furthermore, this approach can be used to better quantify the impact of projected climate change on liver fluke risk for future studies

Unacylated ghrelin, leptin, and appetite display diurnal rhythmicity in lean adults

Constant routine and forced desynchrony protocols typically remove the effects of behavioral/environmental cues to examine endogenous circadian rhythms, yet this may not reflect rhythms of appetite regulation in the real world. It is therefore important to understand these rhythms within the same subjects under controlled diurnal conditions of light, sleep, and feeding. Ten healthy adults (9 M/1 F, means ±SD: age, 30 ± 10 yr; body mass index, 24.1 ± 2.7 kg·m-2) rested supine in the laboratory for 37 h. All data were collected during the final 24 h of this period (i.e., 0800-0800 h). Participants were fed hourly isocaloric liquid meal replacements alongside appetite assessments during waking before a sleep opportunity from 2200 to 0700 h. Hourly blood samples were collected throughout the 24-h period. Dim light melatonin onset occurred at 2318 ± 46 min. A diurnal rhythm in mean plasma unacylated ghrelin concentration was identified (P = 0.04), with the acrophase occurring shortly after waking (0819), falling to a nadir in the evening with a relative amplitude of 9%. Plasma leptin concentration also exhibited a diurnal rhythm (P < 0.01), with the acrophase occurring shortly after lights-out (0032 h) and the lowest concentrations at midday. The amplitude for this rhythm was 25%. Diurnal rhythms were established in all dimensions of appetite except for sweet preference (P = 0.29), with both hunger (2103 h) and prospective food consumption (1955 h) reaching their peak in the evening before falling to their nadir shortly after waking. Under controlled diurnal conditions, simultaneous measurement of leptin, unacylated ghrelin, and subjective appetite over a 24-h period revealed rhythmicity in appetite regulation in lean, healthy humans.NEW & NOTEWORTHY Simultaneous assessment of subjective appetite, unacylated ghrelin, and leptin was carried out over a continuous 37-h protocol for the first time under conditions of controlled light, sleep, and feeding in healthy, lean adults. Rhythms were observed in unacylated ghrelin, leptin, and components of subjective appetite, such as hunger, prospective consumption, and fullness. Concurrent measurement of rhythms in these variables is important to fully understand the temporal relationships between components of appetite as well as the influence of diurnal factors such as sleep, light, and feeding

Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association

Background: Radiation safety is an essential component in the treatment of patients with thyroid diseases by 131I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. Methods: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection recommendations formed the basic structure of recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. Results: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with 131I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. Conclusion: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with 131I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with 131I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90492/1/thy-2E2010-2E0403.pd

The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis

The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS

IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti–IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23–driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes

The potential and value of objective eye tracking in the ophthalmology clinic

Numerous research studies have demonstrated the scope and value of eye movement recording (EMR). There is now potential for EMR to be helpful in a range of clinical contexts and it could be developed as a routine part of the repertoire of clinical investigations offered by the NHS, at least in tertiary centres. We highlight potential uses and challenges below, as a prelude to further development and debat