Digital Cognitive Behavioral Therapy for Insomnia in Women With Chronic Migraines

Objective/Background: Insomnia commonly co-occurs with chronic migraines (CM). Non-pharmacological treatments for insomnia in CM patients remain understudied. This is a proof-of-concept study, which aims to evaluate the feasibility, acceptability, and preliminary efficacy of a digital cognitive behavioral therapy for insomnia (dCBT-I) for individuals with CM and insomnia (CM-I) in the United States. Methods: We recruited 42 females with CM-I symptoms from a U.S.-based observational cohort and from the general population via advertisements. Within a multiple baseline design, participants were randomized to receive dCBT-I after 2, 4, or 6 weeks of completing baseline sleep diaries. DCBT-I was scrutinized against benchmarks for completion rates (≥90% to complete dCBT-I), acceptability (≥80% to find dCBT-I acceptable), and posttreatment changes in insomnia symptoms (≥50% indicating a clinically relevant improvement in their insomnia symptoms). As a secondary measure, we also reported percentage of individuals reverting to episodic migraines. Results: Out of 42 randomized, 35 (83.3%) completed dCBT-I within the 12 weeks provided. Of these completers, 33 (94.3%) reported being satisfied (n = 16) or very satisfied (n = 17) with treatment. Additionally, 65.7% of completers responded to treatment as per universally accepted criteria for insomnia. Lastly, 34% of completers reverted from CM to episodic migraine. Conclusion: This study provides evidence for the feasibility and acceptability of dCBT-I in patients with CM-I complaints. Effects of improving insomnia and migraines were suggested. These results indicate that a randomized controlled trial is needed to determine the efficacy of dCBT-I in CM patients

Gamma-ray Observations Under Bright Moonlight with VERITAS

Imaging atmospheric Cherenkov telescopes (IACTs) are equipped with sensitive photomultiplier tube (PMT) cameras. Exposure to high levels of background illumination degrades the efficiency of and potentially destroys these photo-detectors over time, so IACTs cannot be operated in the same configuration in the presence of bright moonlight as under dark skies. Since September 2012, observations have been carried out with the VERITAS IACTs under bright moonlight (defined as about three times the night-sky-background (NSB) of a dark extragalactic field, typically occurring when Moon illumination > 35%) in two observing modes, firstly by reducing the voltage applied to the PMTs and, secondly, with the addition of ultra-violet (UV) bandpass filters to the cameras. This has allowed observations at up to about 30 times previous NSB levels (around 80% Moon illumination), resulting in 30% more observing time between the two modes over the course of a year. These additional observations have already allowed for the detection of a flare from the 1ES 1727+502 and for an observing program targeting a measurement of the cosmic-ray positron fraction. We provide details of these new observing modes and their performance relative to the standard VERITAS observations

Digital methods to enhance the usefulness of patient experience data in services for long-term conditions: the DEPEND mixed-methods study

Background Collecting NHS patient experience data is critical to ensure the delivery of high-quality services. Data are obtained from multiple sources, including service-specific surveys and widely used generic surveys. There are concerns about the timeliness of feedback, that some groups of patients and carers do not give feedback and that free-text feedback may be useful but is difficult to analyse. Objective To understand how to improve the collection and usefulness of patient experience data in services for people with long-term conditions using digital data capture and improved analysis of comments. Design The DEPEND study is a mixed-methods study with four parts: qualitative research to explore the perspectives of patients, carers and staff; use of computer science text-analytics methods to analyse comments; co-design of new tools to improve data collection and usefulness; and implementation and process evaluation to assess use of the tools and any impacts. Setting Services for people with severe mental illness and musculoskeletal conditions at four sites as exemplars to reflect both mental health and physical long-terms conditions: an acute trust (site A), a mental health trust (site B) and two general practices (sites C1 and C2). Participants A total of 100 staff members with diverse roles in patient experience management, clinical practice and information technology; 59 patients and 21 carers participated in the qualitative research components. Interventions The tools comprised a digital survey completed using a tablet device (kiosk) or a pen and paper/online version; guidance and information for patients, carers and staff; text-mining programs; reporting templates; and a process for eliciting and recording verbal feedback in community mental health services. Results We found a lack of understanding and experience of the process of giving feedback. People wanted more meaningful and informal feedback to suit local contexts. Text mining enabled systematic analysis, although challenges remained, and qualitative analysis provided additional insights. All sites managed to collect feedback digitally; however, there was a perceived need for additional resources, and engagement varied. Observation indicated that patients were apprehensive about using kiosks but often would participate with support. The process for collecting and recording verbal feedback in mental health services made sense to participants, but was not successfully adopted, with staff workload and technical problems often highlighted as barriers. Staff thought that new methods were insightful, but observation did not reveal changes in services during the testing period. Conclusions The use of digital methods can produce some improvements in the collection and usefulness of feedback. Context and flexibility are important, and digital methods need to be complemented with alternative methods. Text mining can provide useful analysis for reporting on large data sets within large organisations, but qualitative analysis may be more useful for small data sets and in small organisations. Limitations New practices need time and support to be adopted and this study had limited resources and a limited testing time. Future work Further research is needed to improve text-analysis methods for routine use in services and to evaluate the impact of methods (digital and non-digital) on service improvement in varied contexts and among diverse patients and carers. Funding This project was funded by the NIHR Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 28. See the NIHR Journals Library website for further project information

The G0 Experiment: Apparatus for Parity-Violating Electron Scattering Measurements at Forward and Backward Angles

In the G0 experiment, performed at Jefferson Lab, the parity-violating elastic scattering of electrons from protons and quasi-elastic scattering from deuterons is measured in order to determine the neutral weak currents of the nucleon. Asymmetries as small as 1 part per million in the scattering of a polarized electron beam are determined using a dedicated apparatus. It consists of specialized beam-monitoring and control systems, a cryogenic hydrogen (or deuterium) target, and a superconducting, toroidal magnetic spectrometer equipped with plastic scintillation and aerogel Cerenkov detectors, as well as fast readout electronics for the measurement of individual events. The overall design and performance of this experimental system is discussed.Comment: Submitted to Nuclear Instruments and Method

Particle-Vortex Duality and the Modular Group: Applications to the Quantum Hall Effect and Other 2-D Systems

We show how particle-vortex duality implies the existence of a large non-abelian discrete symmetry group which relates the electromagnetic response for dual two-dimensional systems in a magnetic field. For conductors with charge carriers satisfying Fermi statistics (or those related to fermions by the action of the group), the resulting group is known to imply many, if not all, of the remarkable features of Quantum Hall systems. For conductors with boson charge carriers (modulo group transformations) a different group is predicted, implying equally striking implications for the conductivities of these systems, including a super-universality of the critical exponents for conductor/insulator and superconductor/insulator transitions in two dimensions and a hierarchical structure, analogous to that of the quantum Hall effect but different in its details. Our derivation shows how this symmetry emerges at low energies, depending only weakly on the details of dynamics of the underlying systems.Comment: 22 pages, LaTeX, 2 figures, uses revte

Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) demonstrates role in hippocampal CA1 physiology

Pathological loss-of-function mutations in cyclin-dependent kinase-like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), a rare and severe neurodevelopmental disorder associated with severe and medically refractory early-life epilepsy, motor, cognitive, visual, and autonomic disturbances in the absence of any structural brain pathology. Analysis of genetic variants in CDD has indicated that CDKL5 kinase function is central to disease pathology. CDKL5 encodes a serine-threonine kinase with significant homology to GSK3β, which has also been linked to synaptic function. Further, Cdkl5 knock-out rodents have increased GSK3β activity and often increased long-term potentiation (LTP). Thus, development of a specific CDKL5 inhibitor must be careful to exclude cross-talk with GSK3β activity. We synthesized and characterized specific, high-affinity inhibitors of CDKL5 that do not have detectable activity for GSK3β. These compounds are very soluble in water but blood-brain barrier penetration is low. In rat hippocampal brain slices, acute inhibition of CDKL5 selectively reduces postsynaptic function of AMPA-type glutamate receptors in a dose-dependent manner. Acute inhibition of CDKL5 reduces hippocampal LTP. These studies provide new tools and insights into the role of CDKL5 as a newly appreciated key kinase necessary for synaptic plasticity. Comparisons to rodent knock-out studies suggest that compensatory changes have limited the understanding of the roles of CDKL5 in synaptic physiology, plasticity, and human neuropathology

Chemical synergy between ionophore PBT2 and zinc reverses antibiotic resistance

The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.IMPORTANCE The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you."Lisa Bohlmann, David M. P. De Oliveira, Ibrahim M. El-Deeb, Erin B. Brazel, Nichaela Harbison-Pric

Angiopoietin-1 promotes functional neovascularization that relieves ischemia by improving regional reperfusion in a swine chronic myocardial ischemia model

10.1007/s11373-006-9082-xJournal of Biomedical Science134579-59

Upper limits from five years of blazar observations with the VERITAS Cherenkov telescopes

Between the beginning of its full-scale scientific operations in 2007 and 2012, the VERITAS Cherenkov telescope array observed more than 130 blazars; of these, 26 were detected as very-high-energy (VHE; E > 100 GeV) γ-ray sources. In this work, we present the analysis results of a sample of 114 undetected objects. The observations constitute a total live-time of ~570 hr. The sample includes several unidentified Fermi-Large Area Telescope (LAT) sources (located at high Galactic latitude) as well as all the sources from the second Fermi-LAT catalog that are contained within the field of view of the VERITAS observations. We have also performed optical spectroscopy measurements in order to estimate the redshift of some of these blazars that do not have spectroscopic distance estimates. We present new optical spectra from the Kast instrument on the Shane telescope at the Lick observatory for 18 blazars included in this work, which allowed for the successful measurement or constraint on the redshift of four of them. For each of the blazars included in our sample, we provide the flux upper limit in the VERITAS energy band. We also study the properties of the significance distributions and we present the result of a stacked analysis of the data set, which shows a 4σ excess