Equivalence of RABBITT and streaking delays in attosecond-time-resolved photoemission spectroscopy at solid surfaces

Gebauer A, Neb S, Enns W, Stadtmüller B, Aeschlimann M, Pfeiffer W. Equivalence of RABBITT and streaking delays in attosecond-time-resolved photoemission spectroscopy at solid surfaces. Applied Sciences. 2019;9(3): 592.The dynamics of the photoelectric effect in solid-state systems can be investigated via attosecond-time-resolved photoelectron spectroscopy. This article provides a comparison of delay information accessible by the two most important techniques, attosecond streaking spectroscopy and reconstruction of attosecond beating by interference of two-photon transitions (RABBITT) at solid surfaces, respectively. The analysis is based on simulated time-resolved photoemission spectra obtained by solving the time-dependent Schrödinger equation in a single-active-electron approximation. We show a continuous transition from the few-cycle RABBITT regime to the streaking regime as two special cases of laser-assisted photoemission. The absolute delay times obtained by both methods agree with each other, within the uncertainty limits for kinetic energies >10 eV. Moreover, for kinetic energies >10 eV, both streaking delay time and RABBITT delay time coincide with the classical time of flight for an electron propagating from the emitter atom to the bulk-vacuum interface, with only small deviations of less than 4 as due to quantum mechanical interference effects

The Costs of Crime Associated with Stimulant Use in a Canadian Setting

Background: Costs attributable to criminal activity are a major component of the economic burden of substance use disorders, yet there is a paucity of empirical evidence on this topic. Our aim was to estimate the costs of crime associated with different forms and intensities of stimulant use. Methods: Retrospective cohort study, including individuals from three prospective cohorts in Vancouver, Canada, measured biannually (2011-2015), reporting stimulant use at baseline assessment. Monthly crime costs included policing, court, corrections, and criminal victimization (2016 CAD). We estimated monthly crime costs associated with mutually exclusive categories of crack, cocaine, methamphetamine, and polystimulant use, stratified by daily/non-daily use, relative to stimulant abstinence, as well as the independent effects of treatment (opioid agonist (OAT) and other addiction treatment). We used a two part model, capturing the probability of criminal activity and costs of crime with generalized linear logistic and gamma regression models, respectively, controlling for age, gender, education, homelessness, mental health issues, employment, prior incarceration, alcohol and opioid use. Results: The study sample included 1,599 individuals (median age 39, 65.9% male) assessed over 5299 biannual interviews. Estimates of associated monthly crime costs ranged from $5449 [95$2180, $8719] for non-daily polystimulant use, to$8893 [$4196, id="mce_marker"3,589] for daily polystimulant use. Cost differences between daily/non-daily use, injection/non-injection, and stimulant type were not statistically significant. Drug treatment was not associated with lower monthly crime costs in our sample. Conclusions: Substantial crime-related costs were associated with stimulant use, emphasizing the urgency for development and implementation of efficacious treatment regimens

Large-Scale simulations of plastic neural networks on neuromorphic hardware

SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Rather than using bespoke analog or digital hardware, the basic computational unit of a SpiNNaker system is a general-purpose ARM processor, allowing it to be programmed to simulate a wide variety of neuron and synapse models. This flexibility is particularly valuable in the study of biological plasticity phenomena. A recently proposed learning rule based on the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm offers a generic framework for modeling the interaction of different plasticity mechanisms using spiking neurons. However, it can be computationally expensive to simulate large networks with BCPNN learning since it requires multiple state variables for each synapse, each of which needs to be updated every simulation time-step. We discuss the trade-offs in efficiency and accuracy involved in developing an event-based BCPNN implementation for SpiNNaker based on an analytical solution to the BCPNN equations, and detail the steps taken to fit this within the limited computational and memory resources of the SpiNNaker architecture. We demonstrate this learning rule by learning temporal sequences of neural activity within a recurrent attractor network which we simulate at scales of up to 2.0 × 104 neurons and 5.1 × 107 plastic synapses: the largest plastic neural network ever to be simulated on neuromorphic hardware. We also run a comparable simulation on a Cray XC-30 supercomputer system and find that, if it is to match the run-time of our SpiNNaker simulation, the super computer system uses approximately 45× more power. This suggests that cheaper, more power efficient neuromorphic systems are becoming useful discovery tools in the study of plasticity in large-scale brain models

Model Cortical Association Fields Account for the Time Course and Dependence on Target Complexity of Human Contour Perception

Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas) distributed among groups of randomly rotated fragments (clutter). The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms), followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Synthesis and Applications of Cyclobutenes

Our group is interested in cyclobutene analogs of fatty acids as reactive coatings, potential antibiotics, and as a new class of bioconjugate linkers. A convenient synthesis of this class of molecules was previously reported from our lab. However, ammonia, a key reagent in the earlier route, was recently reclassified as a highly corrosive gas requiring highly specialized equipment for storage and handling. The goal of this research was to find a convenient synthesis for the formation of cyclobutene that did not involve the use of ammonia. The other part of this thesis describes the preparation of a short chain cyclobutene fatty acid as a substrate for conjugation to an amino acid as part of a collaboration targeting the synthesis of proteins, which could be selectively modified using the cyclobutene/tetrazine click reaction. Advisor: Patrick H. Dussaul

Geographic variation in the costs of medical care for people living with HIV in British Columbia, Canada

Background: Regional variation in medical care costs can indicate heterogeneity in clinical practice, inequities in access, or inefficiencies in service delivery. We aimed to estimate regional variation in medical costs for people living with HIV (PLHIV), adjusting for demographics and case-mix. Methods: We conducted a retrospective cohort study using linked health administrative databases of PLHIV, from 2010 to 2014, in British Columbia (BC), Canada. Quarterly health care costs (2018 CAD) were derived from inpatient, outpatient, prescription drugs, antiretroviral therapy (ART), and HIV diagnostics. We used a two-part model with a logit link for the probability of incurring costs, and a log link and gamma distribution for observations with positive costs. We also estimated quarterly utilization rates for hospitalization-, physician billing- and prescription drug-days. Primary variables were indicators of individuals’ Health Service Delivery Area (HSDA). We adjusted cost and utilization estimates for demographic characteristics, HIV-disease progression, and comorbidities. Results: Our cohort included 9577 PLHIV (median age 45.5 years, 80% male). Adjusted total quarterly costs for all 16 HSDAs were within 20% of the provincial mean, 8/16 for hospitalization costs, 16/16 for physician billing costs and 10/16 for prescription drug costs. Northern Interior and Northeast HSDAs had 38 and 44% lower quarterly non-ART prescription drug costs, and 2 and 5% higher quarterly inpatient costs, respectively. Conclusions: We observed limited variation in medical care costs and utilization among PLHIV in BC. However, lower levels of outpatient care and higher levels of inpatient care indicate possible barriers to accessing care among PLHIV in the most rural regions of the province.Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofReviewedFacult

A cost benefit analysis of a virtual overdose monitoring service/mobile overdose response service: the national overdose response service

Abstract Background The overdose crisis continues across Canada which calls for novel harm reduction strategies. Previous research indicates that a majority of eHealth solutions are cost-effective however current literature on the cost-benefit of eHealth for harm reduction is sparse. The National Overdose Response Service (NORS) is a Canada-wide telephone-based harm reduction service. Service users can call the phone number and connect to a peer who can virtually monitor the substance use session and dispatch appropriate interventions in the case of overdose. Objectives of the research/project We aim to assess the cost-benefit of NORS by comparing the estimated cost-savings from prevented overdose mortality to the operating costs of the program, alongside healthcare costs associated with its operation. Methods Data around systems costs and operational costs were gathered for our calculations. Our primary outcome was cost-benefit ratios, derived from estimates and models of mortality rates in current literature and value of life lost. We presented our main results across a range of values for costs and the probability of death following an unwitnessed overdose. These values were utilized to calculate cost-benefit ratios and value per dollar spent on service provision by NORS over the length of the program’s operation (December 2020–2022). Results Over the total funded lifespan of the program, and using a Monte Carlo estimate, the benefit-to-cost ratio of the NORS program was 8.59 (1.53–15.28) per dollar spent, depending on estimated mortality rates following unwitnessed overdose and program operation costs. Further, we conservatively estimate that early community-based naloxone intervention results in healthcare system savings of $4470.82 per overdose response. Conclusions We found the NORS program to have a positive benefit-to-cost ratio when the probability of death following an unwitnessed overdose was greater than 5%. NORS and potentially other virtual overdose monitoring services have the potential to be cost-effective solutions for managing the drug poisoning crisis