A new near-infrared direct acceleration mechanism driven by Laguerre–Gaussian laser is proposed to stably accelerate and concentrate electron slice both in longitudinal and transversal directions in vacuum. Three-dimensional simulations show that a 2-μm circularly polarized ${\mathrm{LG}}_p^l$ (p = 0, l = 1, σz = −1) laser can directly manipulate attosecond electron slices in additional dimensions (angular directions) and give them annular structures and angular momentums. These annular vortex attosecond electron slices are expected to have some novel applications such as in the collimation of antiprotons in conventional linear accelerators, edge-enhancement electron imaging, structured X-ray generation, and analysis and manipulation of nanomaterials.

We investigate incumbent brands’ response to entry and increased competition in a large retail setting. We extend the nonprice competition and manufacturer stocking literatures by examining if incumbent brands increase quality, specifically increasing the number of varieties (product-line length), in response to entry of a new local brand in the ice cream market. We use the entry of a new, local, super-premium ice cream brand in a large supermarket chain as a quasi-natural experiment and empirically examine if incumbent ice cream brands increased the product-line length in stores carrying the new brand. Using Poisson difference-in-differences estimators, we find that incumbent brands increased the number of varieties offered by 0.9 (3 percent) after the new brand's entry, with most of the responses coming from super-premium ice cream, which increased the number of varieties offered by 2.9 (12 percent) product choices. These findings contribute new insights into quality changes, manufacturer stocking decisions, and nonprice competition associated with entry of a local brand into the food retail sector.

ABSTRACT IMPACT: Our data identify a novel candidate for combination strategy in melanoma treatment, and can inform clinicians in their decision-making process regarding therapeutic intervention for melanoma patients. OBJECTIVES/GOALS: Soluble adenylyl cyclase (sAC) is a novel source of cyclic AMP (cAMP). In melanoma, nuclear sAC localization has an established diagnostic utility and we newly found that nuclear sAC functions as a tumor suppressor by inhibiting Hippo pathway, which affects treatment response. Here, we examine the effect of nuclear sAC on melanoma treatment response. METHODS/STUDY POPULATION: We developed a doxycycline inducible system for increasing sAC activity only in the nucleus. We assessed whether nuclear sAC activity affects treatment response, using BRAFV600 human melanoma cell lines. Using a clonogenic assay, we examined how nuclear sAC activity affects growth inhibition in the presence of a BRAF inhibitor, vemurafenib. Our findings will be confirmed in vivo using tumor xenografts. After tumor formation in NSG mice, mice will be randomized to be fed normal or doxycycline chow for nuclear sAC induction, then subdivided to receive vehicle or vemurafenib to examine the effect of nuclear sAC activity on treatment response in vivo. We will also compare melanoma biopsies collected before and after treatment with BRAF inhibitors to assess how nuclear sAC staining affects tumor morphology in vivo. RESULTS/ANTICIPATED RESULTS: So far, nuclear sAC activity has rendered SkMel178 and M263 cell lines more susceptible to vemurafenib. Cell viability was inversely correlated both with vemurafenib and with doxycycline concentration. Cell viability after vemurafenib treatment was dramatically reduced when nuclear sAC was activated. It appears that nuclear sAC enhances the sensitivity of BRAF mutant melanomas to vemurafenib in vitro. We anticipate that xenografts of these cells in mice will be more susceptible to vemurafenib when nuclear sAC is activated. We also anticipate that positive nuclear sAC staining will correlate with a favorable response to therapy. DISCUSSION/SIGNIFICANCE OF FINDINGS: Targeted therapy with BRAF inhibitors is used in late-stage melanomas, but its use is limited as patients invariably acquire resistance. Here, we identified nuclear sAC activation as a novel candidate for combination strategy. Our data will also inform clinicians how best to integrate this biomarker into their decision-making regarding therapy.

Establishing accurate population size estimates (PSE) is important for prioritising and planning provision of services. Multiple source capture−recapture sampling method increases PSE accuracy and reliability. In August 2018, the three-source capture−recapture (3S-CRC) method was employed with a stringent assumption of sample independence to estimate the number of female sex workers (FSW) in Rwanda. Using Rwanda 2017 FSW hotspots mapping data, street and venue-based FSW were sampled at the sector level of each province and tagged with two unique gifts. Each capture was completed within one week to minimise FSW migration between provinces and recall bias. The three captures had 1042, 1204 and 1488 FSW. There were 111 FSW recaptured between captures 1 and 2; 237 between captures 2 and 3; 203 between captures 1 and 3 and 46 captured in all three. The PSE for street and venue-based FSW in Rwanda lies within 95% credible set: 8328–22 806 with corresponding median of 13 716 FSW. The 3S-CRC technique was low-cost and relatively easy to use for PSE in hard-to-reach populations. This estimate provides the basis for determining the denominators to assess HIV programme performance towards FSW and epidemic control and warrants further PSE for home- and cyber-based FSW in Rwanda.

Coronavirus disease 2019 (COVID-19) is a global health threat. A hospital in Zhuhai adopted several measures in Fever Clinic Management (FCM) to respond to the outbreak of COVID-19. FCM has been proved to be effective in preventing nosocomial cross infection. Faced with the emergency, the hospital undertook creative operational steps in relation to the control and spread of COVID-19, with special focuses on physical and administrative layout of buildings, staff training and preventative procedures. The first operational step was to set up triaging stations at all entrances and then complete a standard and qualified fever clinic, which was isolated from the other buildings within our hospital complex. Secondly, the hospital established its human resource reservation for emergency response and the allocation of human resources to ensure strict and standardised training methods through the hospital for all medical staff and ancillary employees. Thirdly, the hospital divided the fever clinic into partitioned areas and adapted a three-level triaging system. The experiences shared in this paper would be of practical help for the facilities that are encountering or will encounter the challenges of COVID-19, i.e. to prevent nosocomial cross infection among patients and physicians.

In this paper, the authors propose a culture-centred tool called Speculative Ethnography to support the practice of design for the speculative future. Most explorations of tools and techniques of design for the speculative future focus on materialising the speculation. Instead, Speculative Ethnography provides a guideline to help designers define their speculation through the scientific imagination of the plausible future. It ensures the effectiveness of design for the speculative future and supports the interaction of culture and design for the speculative future.

In the digital era, products’ forms do not necessarily follow their function. Design fixation may happen when a designer attempts to generate diverse concepts. New design heuristics for digital design were extracted to support designers in the early conceptual design stage. Ten design heuristics were extracted from 998 RedDot award-winning concept designs (2013-2017) through a five-step process. It was preliminarily tested by four practitioners and proved to have positively influenced their conceptual design.

Background: Since January 1, 2016 2358 people have died from opioid poisoning in Alberta. Buprenorphine/naloxone (bup/nal) is the recommended first line treatment for opioid use disorder (OUD) and this treatment can be initiated in emergency departments and urgent care centres (EDs). Aim Statement: This project aims to spread a quality improvement intervention to all 107 adult EDs in Alberta by March 31, 2020. The intervention supports clinicians to initiate bup/nal for eligible individuals and provide rapid referrals to OUD treatment clinics. Measures & Design: Local ED teams were identified (administrators, clinical nurse educators, physicians and, where available, pharmacists and social workers). Local teams were supported by a provincial project team (project manager, consultant, and five physician leads) through a multi-faceted implementation process using provincial order sets, clinician education products, and patient-facing information. We used administrative ED and pharmacy data to track the number of visits where bup/nal was given in ED, and whether discharged patients continued to fill any opioid agonist treatment (OAT) prescription 30 days after their index ED visit. OUD clinics reported the number of referrals received from EDs and the number attending their first appointment. Patient safety event reports were tracked to identify any unintended negative impacts. Evaluation/Results: We report data from May 15, 2018 (program start) to September 31, 2019. Forty-nine EDs (46% of 107) implemented the program and 22 (45% of 49) reported evaluation data. There were 5385 opioid-related visits to reporting ED sites after program adoption. Bup/nal was given during 832 ED visits (663 unique patients): 7 visits in the 1st quarter the program operated, 55 in the 2nd, 74 in the 3rd, 143 in the 4th, 294 in the 5th, and 255 in the 6th. Among 505 unique discharged patients with 30 day follow up data available 319 (63%) continued to fill any OAT prescription after receiving bup/nal in ED. 16 (70%) of 23 community clinics provided data. EDs referred patients to these clinics 440 times, and 236 referrals (54%) attended their first follow-up appointment. Available data may under-report program impact. 5 patient safety events have been reported, with no harm or minimal harm to the patient. Discussion/Impact: Results demonstrate effective spread and uptake of a standardized provincial ED based early medical intervention program for patients who live with OUD.

The delayed coalescence of drops with the interface between a moving aqueous layer and an oil phase is investigated in a novel flow channel. Drops are released onto oil–aqueous interfaces moving at velocities from $0~\text{cm}~\text{s}^{-1}$ up to $3.4~\text{cm}~\text{s}^{-1}$. The evolution of the drop shape, the film thickness between the drop and the bulk liquid, and the velocities of the drop surface and the bulk interface were measured with planar laser-induced fluorescence. As the interface speed increases, the drop coalescence is delayed. This is attributed to the lubrication pressure that develops in the draining film. This pressure was calculated by using the drop shape and the tangential velocities of the drop surface and the bulk interface, and was shown to increase with the interface velocity. The film forming between the drop and the bulk liquid has a dimple shape, symmetric about the centreline. With increasing interface velocity, the dimple shifts to the front part of the drop, resulting locally in a low pressure, which leads to film rupture. As the film breaks, ‘oil drops on a string’ formations are entrained into the water phase, which is rarely seen when a drop coalesces with a stationary liquid–liquid interface. The velocity fields in the drop were investigated with particle image velocimetry. It is found immediately after reaching the interface that the drops accelerate to reach the interface speed. Initially there is a strong internal circulation in the drops, which decays quickly as the drops approach the speed of the interface.

Although playing of Internet games may lead to Internet gaming disorder (IGD), most game-users do not develop problems and only a relatively small subset experiences IGD. Game playing may have positive health associations, whereas IGD has been repeatedly associated with negative health measures, and it is thus important to understand differences between individuals with IGD, recreational (non-problematic) game use (RGU) and non-/low-frequency game use (NLFGU). Individuals with IGD have shown differences in neural activations from non-gamers, yet few studies have examined neural differences between individuals with IGD, RGU and NLFGU. Eighteen individuals with IGD, 21 with RGU and 19 with NFLGU performed a color-word Stroop task and a guessing task assessing reward/loss processing. Behavioral and functional imaging data were collected and compared between groups. RGU and NLFGU subjects showed lower Stroop effects as compared with those with IGD. RGU subjects as compared to those with IGD demonstrated less frontal cortical activation brain activation during Stroop performance. During the guessing task, RGU subjects showed greater cortico-striatal activations than IGD subjects during processing of winning outcomes and greater frontal brain during processing of losing outcomes. Findings suggest that RGU as compared with IGD subjects show greater executive control and greater activations of brain regions implicated in motivational processes during reward processing and greater cortical activations during loss processing. These findings suggest neural and behavioral features distinguishing RGU from IGD and mechanisms by which RGU may be motivated to play online games frequently yet avoid developing IGD.

Predicting the magnitude of the annual seasonal peak in influenza-like illness (ILI)-related emergency department (ED) visit volumes can inform the decision to open influenza care clinics (ICCs), which can mitigate pressure at the ED. Using ILI-related ED visit data from the Alberta Real Time Syndromic Surveillance Net for Edmonton, Alberta, Canada, we developed (training data, 1 August 2004–31 July 2008) and tested (testing data, 1 August 2008–19 February 2014) spatio-temporal statistical prediction models of daily ILI-related ED visits to estimate high visit volumes 3 days in advance. Our Main Model, based on a generalised linear mixed model with random intercept, incorporated prediction residuals over 14 days and captured increases in observed volume ahead of peaks. During seasonal influenza periods, our Main Model predicted volumes within ±30% of observed volumes for 67%–82% of high-volume days and within 0.3%–21% of observed seasonal peak volumes. Model predictions were not as successful during the 2009 H1N1 pandemic. Our model can provide early warning of increases in ILI-related ED visit volumes during seasonal influenza periods of differing intensities. These predictions may be used to support public health decisions, such as if and when to open ICCs, during seasonal influenza epidemics.

Rumen-protected betaine (RPB) can enhance betaine absorption in the small intestine of ruminants, while betaine can alter fat distribution and has the potential to affect the meat quality of livestock. Hence, we hypothesized that RPB might also affect the meat quality of lambs. Sixty male Hu sheep of similar weight (30.47 ± 2.04 kg) were selected and randomly subjected to five different treatments. The sheep were fed a control diet (control treatment, CTL); 1.1 g/day unprotected-betaine supplemented diet (UPB); or doses of 1.1 g/day (low RPB treatment; L-PB), 2.2 g/day (middle RPB treatment; M-PB) or 3.3 g/day (high RPB treatment; H-PB) RPB-supplemented diet for 70 days. Slaughter performance, meat quality, fatty acid and amino acid content in the longissimus dorsi (LD) muscle, shoulder muscle (SM) and gluteus muscle (GM) were measured. Compared with CTL, betaine (including UPB and RPB) supplementation increased the average daily weight gain (ADG) (P < 0.05) and average daily feed intake (P < 0.01) of lambs. Rumen-protected betaine increased ADG (P < 0.05) compared with UPB. With increasing RPB doses, the eye muscle area of the lambs linearly increased (P < 0.05). Compared with CTL, betaine supplementation decreased water loss (P < 0.05) in SM and increased pH24 in the SM (P < 0.05) and GM (P < 0.05). Compared with UPB, RPB decreased water loss in the GM (P < 0.01), decreased shear force (P < 0.05) in the LD and SM and increased the pH of the meat 24 h after slaughter (pH24). With increasing RPB doses, the shear force and b* value in the LD linearly decreased (P < 0.05), and the pH24 of the meat quadratically increased (P < 0.05). Compared with CTL, betaine supplementation increased the polyunsaturated fatty acid in the GM (P < 0.05). Compared with UPB, RPB supplementation decreased the saturated fatty acid (SFA) content in the LD (P < 0.05) and increased the unsaturated fatty acids (UFA), mono-unsaturated fatty acids and UFA/SFA ratio in the LD (P < 0.05). Compared with CTL, the content of histidine in the LD increased with betaine supplementation. Compared with UPB, RPB supplementation increased the content of total free amino acids and flavor amino acids in the LD of lambs (P < 0.05). With increasing RPB, the isoleucine and phenylalanine contents in the LD linearly increased (P < 0.05). Overall, the data collected indicated that the meat quality of lambs (especially in the LD) improved as a result of betaine supplementation, and RPB showed better effects than those of UPB.