Small-angle X-ray scattering (SAXS) has been widely used as a microstructure characterization technology. In this work, a fully connected dense forward network is applied to inversely retrieve the mean particle size and particle distribution from SAXS data of samples dynamically compressed with high-power lasers and probed with X-ray free electron lasers. The trained network allows automatic acquisition of microstructure information, performing well in predictions on single-species nanoparticles on the theoretical model and in situ experimental data. We evaluate our network by comparing it with other methods, revealing its reliability and efficiency in dynamic experiments, which is of great value for in situ characterization of materials under high-power laser-driven dynamic compression.

We consider the stability of the drawing of a long and thin viscous thread with an arbitrary number of internal holes of arbitrary shape that evolves due to axial drawing, inertia and surface tension effects. Despite the complicated geometry of the boundaries, we use asymptotic techniques to determine a particularly convenient formulation of the equations of motion that is well-suited to stability calculations. We will determine an explicit asymptotic solution for steady states with (a) large surface tension and negligible inertia, and (b) large inertia. In both cases, we will show that complicated boundary layer structures can occur. We will use linear stability analysis to show that the presence of an axisymmetric hole destabilises the flow for finite capillary number and which answers a question raised in the literature. However, our formulation allows us to go much further and consider arbitrary hole structures or non-axisymmetric shapes, and show that any structure with holes will be less stable than the case of a solid axisymmetric thread. For a solid axisymmetric thread, we will also determine a closed-form expression that delineates the unconditional instability boundary in which case the thread is unstable for all draw ratios. We will determine how the detailed effects of the microstructure affect the stability, and show that they manifest themselves only via a single function that occurs in the stability problem and hence have a surprisingly limited effect on the stability.

This paper describes a study of spatially accelerating turbulent flow based on the direct numerical simulation of a flow with longitudinally accelerating moving walls to create a relative acceleration between the fluid and the wall without inducing streamline curvature. The results show a broad similarity to those of previous investigations of spatial acceleration, albeit with some differences. A new interpretation has been proposed considering this spatially accelerating flow to be characterised by the formation of a new boundary layer superimposed on the pre-existing turbulent flow. This is followed by the transition of the flow in response to the development of this new boundary layer. This can be seen as an extension of the transition theory for temporally accelerating turbulent flows (He & Seddighi, J. Fluid Mech., vol. 715, 2013, pp. 60–102). The existing turbulent structures act as disturbances for the new boundary layer similar to the role of free-stream turbulence in bypass transition. This boundary layer modulates the pre-existing near-wall structures, amplifying and elongating the streaks. Some streaks eventually become unstable in a sinuous mechanism reminiscent of streak breakdown in near-wall turbulence, resulting in the formation localised turbulent spots which spread until the entire wall is covered in new turbulence. This interpretation naturally splits the flow into a new boundary layer region and a core (or free-stream) flow with interactions between the two dominating a significant length of the flow development and potentially offers a new explanation for the slow evolution of the turbulent stresses observed previously.

Background: Machine learning (ML) methods hold promise in allowing early detection of dementia. We performed a systematic review to assess the quality of published evidence for using ML methods applied to drawing tests of cognition, and to describe the accuracy of the methods. Methods: Embase, Medline, and Cochrane Central Library databases were searched for potential studies up to December 8, 2018 by four independent reviewers. Included articles satisfied the following criteria: 1) use of ML on 2) a drawing test in order to 3) assess cognition. The quality of evidence was then assessed using GRADE methodology. Results: The initial search yielded 4620 citations. Of these, 64 were eligible for full text review. 18 articles then met inclusion criteria. Median AUC across all models was 0.765, with certain ML algorithms performing better in terms of AUC or diagnostic accuracy. However, based on GRADE, the quality of evidence was deemed very low. Conclusions: ML has been applied by several groups to drawing tests of cognition. The quality of evidence is currently too low to make recommendations on their use. Future work must focus on improving reporting, and using standard algorithms and larger, more diverse datasets to improve comparability and generalizability.

ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.

Background: Greater than 10% of hospitalized MRSA carriers experience serious MRSA infection in the year following discharge. Prevention opportunities have primarily focused on hospital stays; however postdischarge interventions have the potential to reduce morbidity, mortality and healthcare costs. The CLEAR trial found a 30% hazard reduction in postdischarge MRSA infections among patients who had inpatient MRSA cultures and were given postdischarge decolonization (5 days twice-a-month for 6 months) relative to hygiene education alone. We conducted a cost analysis of the CLEAR intervention to quantify the economic implications and understand the value of adopting this MRSA decolonization strategy. Methods: We constructed a decision model to estimate the one-year healthcare utilization and costs associated with postdischarge decolonization relative to hygiene education. Trial results for MRSA infection risk and downstream outcomes (including outpatient and emergency room visits, hospitalizations, related nursing home stays, and postdischarge antibiotics) were used to parameterize the model. Other medical care and prescription drug costs were based on Medicare Fee Schedules, Red Book and the literature. Patient out-of-pocket costs and time costs associated with subsequent infections were from a survey of trial participants experiencing infection (n=405). All costs were reported in 2019 US dollars. The analysis was conducted using healthcare system and societal perspectives. Sensitivity analyses were conducted on key parameters. Results: Among a hypothetical cohort of 1,000 hospitalized MRSA carriers, we estimated that a postdischarge decolonization intervention versus hygiene education would result in at least 36 fewer subsequent MRSA infections (130 vs 93 of 1,000, respectively) and >40 fewer MRSA-attributable healthcare events including 32 hospitalizations and 6 postdischarge nursing home visits over the course of a year. Assuming an intervention cost of $185 per individual, the program would result in an overall cost savings of $469,000 per 1,000 MRSA carriers undergoing decolonization. This translates to an overall savings of $13,200 per infection averted and $9,000 per infection averted from the healthcare system perspective. Even assuming a lower infection rate or a less effective intervention (15% reduction in infections vs 30% in the CLEAR trial), or a more expensive (up to $653 per patient) intervention, a decolonization program would still result in cost-savings for society, the healthcare system and patients. Conclusions: In addition to health benefits of preventing infections, postdischarge decolonization of MRSA carriers yields substantial savings to society and the healthcare system. Future recommendations for reducing postdischarge MRSA-related disease among MRSA carriers should consider routine decolonization at hospital discharge.

Funding: This study was supported by a grant from the AHRQ Healthcare-Associated Infections Program (R01HS019388) and by the University of California Irvine Institute for Clinical and Translational Science, which was funded by a grant from the NIH Clinical and Translational Sciences Award program (UL1 TR000153).

Disclosures: Dr. Huang reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), Mölnlycke, 3M, Clorox, Xttrium Laboratories, and Medline. Ms. Singh reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline. Dr. Rashid, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker(Sage Products), Clorox, and Medline. Dr. McKinnell reports receiving grant support to his institution from Melinta Therapeutics, and fees for serving as a research investigator from Lightship, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories and Medline, and serving as cofounder of Expert Stewardship. Dr. Miller reports receiving grant support from Gilead Sciences, Merck, Abbott, Cepheid, Genentech, Atox Bio, and Paratek Pharmaceuticals, grant support and fees for serving on an advisory board from Achaogen and grant support, consulting fees, and fees for serving on an advisory board from Tetraphase and conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline.

Cakes and biscuits are widely consumed foods and are important contributors of energy, total and saturated fat and sugar in British diets. So far, the UK government has prompted the food industry to reduce energy density in cakes and biscuits mainly through sugar reformulation. However, a government led evaluation has shown that reducing only sugar has lowered energy density minimally. To assess whether total and saturated fat reformulation could be an additional and more effective mechanism for reducing product energy density we conducted a cross-sectional survey of pre-packed cakes and biscuits available in nine UK supermarkets. We collected nutrition information from product packaging. In cakes (n = 381), the mean total fat content was 17.9 ± 5.2g/100 g (39% of the overall energy); range (1.4–35.6g/100g). The average saturated fat content in cakes was 5.9 ± 3.4g/100 g (13% of the overall energy); range (0.3–20g/100g). The average sugar content in cakes was 36.6 ± 7.6 (34% of the overall energy); range (11.3–62.0g/100g). In biscuits (n = 481) the mean total fat content was 21.8g ± 6.3g/100 g (40% of the overall energy); range (0.7–38.9g/100g) and the average saturated fat content was 11.4 ± 4.9 g/100 g (23% of the overall energy); range (0.3–22.3g/100g). The average sugar content in biscuits was 30.0 ± 9.2 (23% of the overall energy); range (12.0–74.0g/100g). In both cakes and biscuits total and saturated fat, but not sugar content, was positively correlated with energy density. According to the nutrient profiling system used by the government, 57% of cakes and 75% of biscuits would receive a red (high) label for total fats; 54% of cakes and 88% of biscuits and would receive a red label for saturated fat.

Our results show that cakes and biscuits sold in UK supermarkets are high in total and saturated fat, and that fat content contributes substantially to product energy density. We observed a large variation in total and saturated fat content within each product category. This finding indicates that reformulation to reduce total and saturated fat and energy density is possible as some manufacturers are already producing cake and biscuits with a more healthful nutrient composition and lower energy density. Fat reformulation in cakes and biscuits and similar products would effectively reduce energy density and calorie intake and thereby prevent obesity. We recommend that fat reformulation should be implemented simultaneously with sugar reformulation and to be focussed where possible on saturated fat, as this will have the additional and independent beneficial effect of lowering LDL cholesterol.

This study aims to observe the efficacy of a new recovery technology of cerebrospinal fluid flow obstacle for the treatment of subarachnoid haemorrhage with intracranial aneurysms, and review the overview of this new technology and new surgical instruments.

Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), are a group of fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrPC) into a self-feplicating and proteinase K (PK)-resistant conformer, scrapie PrP (PrPSc). Aggregates of PrPSc around neurons lead to neuropathologyical change including neuronal loss, astrogliosis, spongiform degeneration and deposition of amyloid plaques. Currently no effective treatment for prion disease exists. The development of novel therapeutic strategies against prion diseases has become a priority. Several reports have demonstrated that passive and active immune-based therapy can significantly prolong the incubation period of prionoses in vivo, and also some anti-PrP monoclonal can prevent PrP peptide toxicity in vitro. In this study, we have first time identified and purified anti-PrP antibodies from human intravenous immunoglobulin (IVIG) by using PrP peptide affinity chromatography column. The ratio of anti-PrP antibody and IVIG is about 1:1200. In vitro study indicates these anti-PrP antibodies strongly block PrP A117V peptide fibril formation and disrupt formation of fibrillar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of PrP A117V peptide in cultured rat cerebellar granule neuron cultures (CGN). In contrast, immunoglobulins depleted of anti-PrP antibodies had little effect on PrP fibril formation or protection of neuronal cells. Our study suggests that human anti-PrP antibodies may interfere with the pathogenesis of prion disease and these purified antibodies may be a potential therapeutic agent to prevent or slow prion disease progression.