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

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program

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

Detection of Acute Brain Injury in Intensive Care Unit Patients on ECMO Support Using Ultra-Low-Field Portable MRI: A Retrospective Analysis Compared to Head CT

Early detection of acute brain injury (ABI) is critical to intensive care unit (ICU) patient management and intervention to decrease major complications. Head CT (HCT) is the standard of care for the assessment of ABI in ICU patients; however, it has limited sensitivity compared to MRI. We retrospectively compared the ability of ultra-low-field portable MR (ULF-pMR) and head HCT, acquired within 24 h of each other, to detect ABI in ICU patients supported on extracorporeal membrane oxygenation (ECMO). A total of 17 adult patients (median age 55 years; 47% male) were included in the analysis. Of the 17 patients assessed, ABI was not observed on either ULF-pMR or HCT in eight patients (47%). ABI was observed in the remaining nine patients with a total of 10 events (8 ischemic, 2 hemorrhagic). Of the eight ischemic events, ULF-pMR observed all eight, while HCT only observed four events. Regarding hemorrhagic stroke, ULF-pMR observed only one of them, while HCT observed both. ULF-pMR outperformed HCT for the detection of ABI, especially ischemic injury, and may offer diagnostic advantages for ICU patients. The lack of sensitivity to hemorrhage may improve with modification of the imaging acquisition program