Tau Aggregation Inhibitor Therapy : An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease

ACKNOWLEDGMENTS We thank patients and their caregivers for their participation in the study and are indebted to all the investigators involved in the study, particularly Drs. Douglas Fowlie and Donald Mowat for their helpful contributions to the clinical execution of the study in Scotland. We thank Sharon Eastwood, Parexel, for assistance in preparing initial drafts of the manuscript. We acknowledge constructive comments provided by Professors G. Wilcock and S. Gauthier on drafts of the article. CMW, CRH, and JMDS are officers of, and hold beneficial interests in, TauRx Therapeutics. RTS, PB, KK, and DJW are paid consultants to TauRx Therapeutics. The study was financed entirely by TauRx TherapeuticsPeer reviewedPublisher PD

Sonographic and cyst fluid cytological changes after EUS-guided pancreatic cyst ablation

Background and Aims The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study is to evaluate morphological, cytological and change in cyst fluid DNA after PCA. Methods In a prospective single center study, consecutive patients with suspected benign 10 to 50 mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete (CR), partial (PR), or persistent with <5%, 5% to 25%, and 25% of the original cyst volume, respectively. Results 36 patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28) and CR occurred in 19 (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, and increased or appearance of macrophages in 24% and inflammatory cells in 15%. Post-ablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytological features. In the CR group, mean DNA quantity was significantly increased after ablation (p=0.023) without a change in quality (p=0.136) Conclusions EUS-PCA induces morphological and cytological changes of the pancreatic cysts none of which appear to predict overall imaging-defined response to ablation

Collective Value QoS: A Performance Measure Framework for Distributed Heterogeneous Networks

When users' tasks in a distributed heterogeneous computing environment are allocated resources, and the total demand placed on system resources by the tasks, for a given interval of time, exceeds the resources available, some tasks will receive degraded service, receive no service at all, or may be dropped from the system. One part of a measure to quantify the success of a resource management system (RMS) in such an environment is the collective value of the tasks completed during an interval of time, as perceived by the user, the application, or the policy maker. For the case where a task may be a data communication request, the collective value of data communication requests that are satisfied during an interval of time is measured. The Flexible Integrated System Capability (FISC) measure defined here is one way of obtaining a multi-dimensional measure for quantifying this collective value. While the FISC measure itself is not sufficient for scheduling purposes, it can be a critical part of a scheduler or a scheduling heuristic. The primary contribution of this work is providing a way to measure the collective value accrued by an RMS using a broad range of attributes and to construct a flexible framework that can be extended for particular problem domains.DARPA/ITO Quorum ProgramDARPA/ISO BADD ProgramOffice of Naval Research under ONR grant number N00014-97-1-0804DARPA/ITO AICE program under contract numbers DABT63-99-C-0010 and DABT63-99-C-0012DARPA/ITO Quorum ProgramDARPA/ISO BADD ProgramOffice of Naval Research under ONR grant number N00014-97-1-0804DARPA/ITO AICE program under contract numbers DABT63-99-C-0010 and DABT63-99-C-0012Approved for public release; distribution is unlimited

Functional impairment matters in the screening and diagnosis of gaming disorder

This commentary responds to Aarseth et al.’s (in press) criticisms that the ICD-11 Gaming Disorder proposal would result in “moral panics around the harm of video gaming” and “the treatment of abundant false-positive cases.” The ICD-11 Gaming Disorder avoids potential “overpathologizing” with its explicit reference to functional impairment caused by gaming and therefore improves upon a number of flawed previous approaches to identifying cases with suspected gaming-related harms. We contend that moral panics are more likely to occur and be exacerbated by misinformation and lack of understanding, rather than proceed from having a clear diagnostic system

Adequacy of therapy for people with both COPD and heart failure in the UK : historical cohort study

Acknowledgments We thank Derek Skinner for his contributions to the data acquisition and handling and Carole Nicholls and Priyanka Raju Konduru for statistical support. Writing and editorial support was provided by Elizabeth V. Hillyer, DVM, supported by Novartis Pharma AG, Basel, Switzerland. Funding This work was supported by Novartis. Employees of the sponsor (listed as authors) participated in the study design, interpretation of the results, writing of the report, and the decision to submit the paper for publication.Peer reviewedPublisher PD

Associations of objectively measured and self-reported sleep duration with carotid artery intima media thickness among police officers

BACKGROUND: We aimed to examine the association of objectively measured and self-reported sleep duration with carotid artery intima media thickness (IMT) among 257 police officers, a group at high risk for cardiovascular disease (CVD). METHODS: Sleep duration was estimated using actigraphic data and through self-reports. The mean maximum IMT was the average of the largest 12 values scanned bilaterally from three angles of the near and far wall of the common carotid, bulb, and internal carotid artery. Linear and quadratic regression models were used to assess the association of sleep duration with IMT. RESULTS: Officers who had fewer than 5 or 8 hr or more of objectively measured sleep duration had significantly higher maximum IMT values, independent of age. Self-reported sleep duration was not associated with either IMT measure. CONCLUSION: Attainment of sufficient sleep duration may be considered as a possible strategy for atherosclerosis prevention among police officers

Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer’s Disease : Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial

The supplementary material is available in the electronic version of this article: http://dx.doi.org/10.3233/JAD-170560. The study was sponsored by TauRx Therapeutics (Singapore). We thank Lon Schneider and Howard Feldman for their contribution to the Scientific Advisory Board. We gratefully acknowledge study investigators and the generosity of study participants. Authors’ disclosures available online (http://j-alz.com/manuscript disclosures/17-0560r3).Peer reviewedPublisher PD

Initial Experiences with Laparoscopy-assisted and Total Laparoscopy for Anatomical Liver Resection: A Preliminary Study

Although laparoscopic surgery has become more popular, its technical difficulties have limited the applications of this technique to liver surgery. We report here on our experience with liver resection with using the laparoscopy-assisted (Lap-Assist) and total laparoscopic (Total-Lap) methods. From April 2001 to June 2003, a total of 20 laparoscopic anatomical resections of the liver were retrospectively reviewed. These were comprised of 10 cases in which the Lap-Assist method was used (these were performed during the early study period), and 10 cases in which the Total-Lap was used (these were done in the later study period). In the Lap-Assist group, the following resections were performed: 7 cases of left lateral sectionectomy, a case of left hemihepatectomy, a case of right hemihepatectomy and a case of open conversion. In the Total-Lap group, 6 cases of left hemihepatectomy and 4 cases of left lateral sectionectomy were performed. The sizes of the incisions were 8.7 cm and 4.6 cm, respectively, (p=0.000). There were no differences in the operation times, the transfusion amounts, the starting days of the patients' diets, the complication rates or the durations of the hospital stay between the two groups. Both the laparoscopy-assisted method and the total laparoscopic method are feasible to use for performing anatomical liver resection

Chiral structures of electric polarization vectors quantified by X-ray resonant scattering

Resonant elastic X-ray scattering (REXS) offers a unique tool to investigate solid-state systems providing spatial knowledge from diffraction combined with electronic information through the enhanced absorption process, allowing the probing of magnetic, charge, spin, and orbital degrees of spatial order together with electronic structure. A new promising application of REXS is to elucidate the chiral structure of electrical polarization emergent in a ferroelectric oxide superlattice in which the polarization vectors in the REXS amplitude are implicitly described through an anisotropic tensor corresponding to the quadrupole moment. Here, we present a detailed theoretical framework and analysis to quantitatively analyze the experimental results of Ti L-edge REXS of a polar vortex array formed in a PbTiO3/SrTiO3 superlattice. Based on this theoretical framework, REXS for polar chiral structures can become a useful tool similar to x-ray resonant magnetic scattering (XRMS), enabling a comprehensive study of both electric and magnetic REXS on the chiral structures.K.T.K., S.Y.P., and D.R.L acknowledge financial support by National Research Foundation of Korea (Grant No. NRF-2020R1A2C1009597, NRF-2019K1A3A7A09033387, and NRF-2021R1C1C1009494). M.M. and R.R. were supported by the Quantum Materials program from the Office of Basic Energy Sciences, US Department of Energy (DE-AC02-05CH11231). V.A.S., J.W.F., and L.W.M. acknowledge the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Award Number DE-SC-0012375 for support to study complex-oxide heterostructure with X-ray scattering. L.W.M. and R.R. acknowledge partial support from the Army Research Office under the ETHOS MURI via cooperative agreement W911NF-21-2-0162. J.Í. acknowledges financial support from the Luxembourg National Research Fund through project FNR/C18/MS/12705883/REFOX. M.A.P.G. was supported by the Czech Science Foundation (project no. 19-28594X). Diamond Light Source, UK, is acknowledged for beamtime on beamline I10 under proposal NT24797. Use of the Advanced Light Source, Lawrence Berkeley National Laboratory, was supported by the U.S. Department of Energy (DOE) under contract no. DE-AC02-05CH11231, and use of the Advanced Photon Source was supported by DOE’s Office of Science under contract DE-AC02-06CH11357