Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

BACKGROUND: While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. RESULTS: Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. CONCLUSION: The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke

Boundary Effects in Chiral Polymer Hexatics

Boundary effects in liquid-crystalline phases can be large due to long-ranged orientational correlations. We show that the chiral hexatic phase can be locked into an apparent three-dimensional N+6 phase via such effects. Simple numerical estimates suggest that the recently discovered "polymer hexatic" may actually be this locked phase.Comment: 4 pages, RevTex, 3 included eps figure

VA residential substance use disorder treatment program providers’ perceptions of facilitators and barriers to performance on pre-admission processes

Abstract Background In the U.S. Department of Veterans Affairs (VA), residential treatment programs are an important part of the continuum of care for patients with a substance use disorder (SUD). However, a limited number of program-specific measures to identify quality gaps in SUD residential programs exist. This study aimed to: (1) Develop metrics for two pre-admission processes: Wait Time and Engagement While Waiting, and (2) Interview program management and staff about program structures and processes that may contribute to performance on these metrics. The first aim sought to supplement the VA’s existing facility-level performance metrics with SUD program-level metrics in order to identify high-value targets for quality improvement. The second aim recognized that not all key processes are reflected in the administrative data, and even when they are, new insight may be gained from viewing these data in the context of day-to-day clinical practice. Methods VA administrative data from fiscal year 2012 were used to calculate pre-admission metrics for 97 programs (63 SUD Residential Rehabilitation Treatment Programs (SUD RRTPs); 34 Mental Health Residential Rehabilitation Treatment Programs (MH RRTPs) with a SUD track). Interviews were then conducted with management and front-line staff to learn what factors may have contributed to high or low performance, relative to the national average for their program type. We hypothesized that speaking directly to residential program staff may reveal innovative practices, areas for improvement, and factors that may explain system-wide variability in performance. Results Average wait time for admission was 16 days (SUD RRTPs: 17 days; MH RRTPs with a SUD track: 11 days), with 60% of Veterans waiting longer than 7 days. For these Veterans, engagement while waiting occurred in an average of 54% of the waiting weeks (range 3–100% across programs). Fifty-nine interviews representing 44 programs revealed factors perceived to potentially impact performance in these domains. Efficient screening processes, effective patient flow, and available beds were perceived to facilitate shorter wait times, while lack of beds, poor staffing levels, and lengths of stay of existing patients were thought to lengthen wait times. Accessible outpatient services, strong patient outreach, and strong encouragement of pre-admission outpatient treatment emerged as facilitators of engagement while waiting; poor staffing levels, socioeconomic barriers, and low patient motivation were viewed as barriers. Conclusions Metrics for pre-admission processes can be helpful for monitoring residential SUD treatment programs. Interviewing program management and staff about drivers of performance metrics can play a complementary role by identifying innovative and other strong practices, as well as high-value targets for quality improvement. Key facilitators of high-performing facilities may offer programs with lower performance useful strategies to improve specific pre-admission processes

Enhancing access to alcohol use disorder pharmacotherapy and treatment in primary care settings: ADaPT-PC.

BACKGROUND: Only 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation components. METHODS/DESIGN: Three large Veterans Health Administration (VHA) facilities are participating in the intervention. The intervention targets stakeholder groups with tailored strategies based on implementation theory and prior research identifying barriers to implementation of AUD pharmacotherapy. Local SUD providers and primary care mental health integration (PCMHI) providers are trained to serve as local implementation/clinical champions and receive external facilitation. PC providers receive access to consultation from local and national clinical champions, educational materials, and a dashboard of patients with AUD on their caseloads for case identification. Veterans with AUD diagnoses receive educational information in the mail just prior to a scheduled PC visit. Effectiveness of the intervention will be evaluated through an interrupted time series with matched controls to monitor change in facility level AUD pharmacotherapy prescribing rates. Following Stetler\u27s four-phase formative evaluation (FE) strategy, FE methods include (1) developmental FE (pre-implementation interviews with champions, PC providers, and Veterans), (2) implementation-focused FE (tracking attendance at facilitation meetings, academic detailing efforts by local champions, and patient dashboard utilization), (3) progress-focused FE (tracking rates of AUD pharmacotherapy prescribing and rates of referral to PCMHI and SUD specialty care), and (4) interpretive FE (post-implementation interviews with champions and PC providers). Analysis of FE data will be guided by the Consolidated Framework for Implementation Research (CFIR). DISCUSSION: If demonstrated to be successful, this implementation strategy will provide a replicable, feasible, and relative low-cost method for integrating AUD treatment services into PC settings, thereby increasing access to AUD treatment

Lift-off dynamics in a simple jumping robot

We study vertical jumping in a simple robot comprising an actuated mass-spring arrangement. The actuator frequency and phase are systematically varied to find optimal performance. Optimal jumps occur above and below (but not at) the robot's resonant frequency $f_0$. Two distinct jumping modes emerge: a simple jump which is optimal above $f_0$ is achievable with a squat maneuver, and a peculiar stutter jump which is optimal below $f_0$ is generated with a counter-movement. A simple dynamical model reveals how optimal lift-off results from non-resonant transient dynamics.Comment: 4 pages, 4 figures, Physical Review Letters, in press (2012

No imminent quantum supremacy by boson sampling

It is predicted that quantum computers will dramatically outperform their conventional counterparts. However, large-scale universal quantum computers are yet to be built. Boson sampling is a rudimentary quantum algorithm tailored to the platform of photons in linear optics, which has sparked interest as a rapid way to demonstrate this quantum supremacy. Photon statistics are governed by intractable matrix functions known as permanents, which suggests that sampling from the distribution obtained by injecting photons into a linear-optical network could be solved more quickly by a photonic experiment than by a classical computer. The contrast between the apparently awesome challenge faced by any classical sampling algorithm and the apparently near-term experimental resources required for a large boson sampling experiment has raised expectations that quantum supremacy by boson sampling is on the horizon. Here we present classical boson sampling algorithms and theoretical analyses of prospects for scaling boson sampling experiments, showing that near-term quantum supremacy via boson sampling is unlikely. While the largest boson sampling experiments reported so far are with 5 photons, our classical algorithm, based on Metropolised independence sampling (MIS), allowed the boson sampling problem to be solved for 30 photons with standard computing hardware. We argue that the impact of experimental photon losses means that demonstrating quantum supremacy by boson sampling would require a step change in technology.Comment: 25 pages, 9 figures. Comments welcom

Time Markers and Temporal Illusions

Peer reviewe

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Long-term health status and trajectories of seriously injured patients: A population-based longitudinal study

Improved understanding of the quality of survival of patients is crucial in evaluating trauma care, understanding recovery patterns and timeframes, and informing healthcare, social, and disability service provision. We aimed to describe the longer-term health status of seriously injured patients, identify predictors of outcome, and establish recovery trajectories by population characteristics.A population-based, prospective cohort study using the Victorian State Trauma Registry (VSTR) was undertaken. We followed up 2,757 adult patients, injured between July 2011 and June 2012, through deaths registry linkage and telephone interview at 6-, 12-, 24-, and 36-months postinjury. The 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3L) was collected, and mixed-effects regression modelling was used to identify predictors of outcome, and recovery trajectories, for the EQ-5D-3L items and summary score. Mean (SD) age of participants was 50.8 (21.6) years, and 72% were male. Twelve percent (n = 333) died during their hospital stay, 8.1% (n = 222) of patients died postdischarge, and 155 (7.0%) were known to have survived to 36-months postinjury but were lost to follow-up at all time points. The prevalence of reporting problems at 36-months postinjury was 37% for mobility, 21% for self-care, 47% for usual activities, 50% for pain/discomfort, and 41% for anxiety/depression. Continued improvement to 36-months postinjury was only present for the usual activities item; the adjusted relative risk (ARR) of reporting problems decreased from 6 to 12 (ARR 0.87, 95% CI: 0.83-0.90), 12 to 24 (ARR 0.94, 95% CI: 0.90-0.98), and 24 to 36 months (ARR 0.95, 95% CI: 0.95-0.99). The risk of reporting problems with pain or discomfort increased from 24- to 36-months postinjury (ARR 1.06, 95% CI: 1.01, 1.12). While loss to follow-up was low, there was responder bias with patients injured in intentional events, younger, and less seriously injured patients less likely to participate; therefore, these patient subgroups were underrepresented in the study findings.The prevalence of ongoing problems at 3-years postinjury is high, confirming that serious injury is frequently a chronic disorder. These findings have implications for trauma system design. Investment in interventions to reduce the longer-term impact of injuries is needed, and greater investment in primary prevention is needed