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In scientific collaborations, technologies have broadened access to scarce scientific and engineering resources. While broader access is often applauded, little attention has been focused on the problem of efficient and equitable resource allocation. This paper presents laboratory experiments designed to compare different allocation mechanisms for access to joint research facilities. Specifically, we study the Vickrey-Clarke-Groves (VCG) auction, a simultaneous ascending auction (the Resource Allocation Design, RAD), and a mechanism based on submitted rankings (Knapsack). Experimental results show that RAD and VCG are both more efficient than Knapsack, while Knapsack achieves a more equal distribution of resources than RAD or VCG. The findings highlight the need for systematic exploration of allocation mechanisms within collaboratories.
Applying a variational analysis, a minimum-enstrophy vortex in three-dimensional (3-D) fluids with continuous stratification is found, under the quasi-geostrophic hypothesis. The buoyancy frequency is held constant. This vortex is an ideal limiting state in a flow with an enstrophy decay while energy and generalized angular momentum remain fixed. The variational method used to obtain two-dimensional (2-D) minimum-enstrophy vortices is applied here to 3-D integral quantities. The solution from the first-order variation is expanded on a basis of orthogonal spherical Bessel functions. By computing second-order variations, the solution is found to be a true minimum in enstrophy. This solution is weakly unstable when inserted in a numerical code of the quasi-geostrophic equations. After a stage of linear instability, nonlinear wave interaction leads to the reorganization of this vortex into a tripolar vortex. Further work will relate our solution with maximal entropy 3-D vortices.
China's cattle trade before 1949 is effectively invisible to historians. With no geographic center, few dominant firms, and little government oversight, cattle trade left behind no clear archive of sources, leaving scholars to the mercy of conjecture and episodic evidence. Combining insights from business and social history, we focused our attention on trade intermediation as the key to understanding the operations of a diffuse trade system. In the absence of a top–down archive, we composited hundreds of local sources on intermediation in cattle trade and remotely interviewed 80 former brokers. These sources revealed large numbers of individuated trade routes, which we break into three types: persistent supply, specialized demand, and resource circulation. Each type of trade called for distinct forms of intermediation with relatively little overlap between specialized networks. This recreation of China's cattle trade reveals a sophisticated market for animal labor that calls into question the direct causal link between imperialist resource extraction and rural immiseration, and suggests the utility of applying tools and perspectives of social history to other sorts of decentered commercial systems.
An increased number of rogue waves, relative to standard distributions, can be induced by unidirectional waves passing over abrupt decreases in water depth. We investigate this phenomenon in a more general setting of multidirectional waves. We examine the influence of the directionality on the occurrence probability of rogue waves using laboratory experiments and fully nonlinear potential flow simulations. Based on the analysis of the statistics of random waves, we find that directional spreading reduces the formation probability of rogue waves relative to unidirectional seas. Nevertheless, for typical values of directional spreading in the ocean ($15^{\circ }\unicode{x2013}30^{\circ }$), our numerical results suggest that there is still a significant enhancement to the number of rogue waves just beyond the top of a depth discontinuity.
This chapter considers the role of advance directives in Malaysia, beginning with a discussion of the legal principles that are likely to apply in the end-of-life decision-making context. We then examine the professional guidance on advance directives published by the Malaysian Medical Council and the Ministry of Health, and highlight points of concern that such guidance has failed to address. The chapter then turns to consideration of the limited empirical data on advance directive awareness in Malaysia, followed by a discussion of the various sociocultural factors that may influence the acceptance of advance directives, with a particular focus on the significant roles played by the family and physicians. Religion as a key influence is also explored in relation to Malaysian attitudes towards advance directives.
Abrupt depth transitions (ADTs) have recently been identified as potential causes of ‘rogue’ ocean waves. When stationary and (close-to-) normally distributed waves travel into shallower water over an ADT, distinct spatially localized peaks in the probability of extreme waves occur. These peaks have been predicted numerically, observed experimentally, but not explained theoretically. Providing this theoretical explanation using a leading-order-physics-based statistical model, we show, by comparing to new experiments and numerical simulations, that the peaks arise from the interaction between linear free and second-order bound waves, also present in the absence of the ADT, and new second-order free waves generated due to the ADT.
This paper develops second-order theory for narrow-banded surface gravity wavepackets experiencing a sudden depth transition based on a Stokes and multiple-scales expansion. As a wavepacket travels over a sudden depth transition, additional wavepackets are generated that propagate freely obeying the linear dispersion relation and arise at both first and second order in wave steepness in a Stokes expansion. In the region near the top of the depth transition, the resulting transient processes play a crucial role. At second order in wave steepness, free and bound waves coexist with different phases. Their different speeds of travel result in a local peak a certain distance after the depth transition. This distance depends on the water depth $h_s$ relative to the carrier wavelength on the shallower side $\lambda _{0s}$. We validate our theory through comparison with fully nonlinear numerical simulations. Experimental validation is provided in a companion paper (Li et al, J. Fluid Mech., 2021, 915, A72). We conjecture that the combination of the local transient peak at second order and the magnitude of the linear free waves provides the explanation for the rogue waves observed after a sudden depth transition reported in a significant number of papers and reviewed in Trulsen etal (J. Fluid Mech., vol. 882, 2020, R2).
Surface gravity wavepackets in intermediate water depth experiencing an abrupt depth decrease are investigated experimentally. The experiments provide validation for the second-order (in steepness) theory for narrow-banded surface gravity wavepackets experiencing a sudden depth transition derived in a companion paper (Li et al., J. Fluid Mech., 2021, 915, A71). We observe the generation of free second-order sub- and superharmonic wavepackets due to the sudden depth transition, in addition to changes to the main (first-order) wavepacket and its second-order bound waves. Locally, just after the step, this leads to the superposition of different wavepacket components. Thereafter, separation occurs because of the different group speeds of the free second-order sub- and superharmonic wavepackets compared with the main packet. Experiments show that the local superposition of waves can lead to significant amplification of wave crests near the top of a step, as predicted by theory. In addition to a step, we also experimentally examine more gradual depth changes in the form of 1 : 1 and 1 : 3 slopes to explore the limits of the theory's validity. Although we find small differences in amplitude and phase comparing these steep slopes with a step, these experiments suggest that the theoretical model derived in Part 1 for wavepackets travelling over a step is applicable to slopes steeper than $1\,{:}\,3$.
Beryl from Xuebaoding, Sichuan Province, western China is known for its unusual tabular habit and W–Sn–Be paragenesis in a greisen-type deposit. The crystals are typically colourless transparent to pale blue, often with screw dislocations of hexagonal symmetry on the (0001) crystal faces. Combining electron microprobe analyses and laser ablation inductively coupled plasma mass spectrometry with single-crystal X-ray diffraction (XRD), correlated with Raman and micro-infrared (IR) spectroscopy and imaging, the crystal chemical characteristics are determined. The contents of Na+ (0.24–0.38 atoms per formula unit (apfu)) and Li+ up to 0.38 apfu are at the high end compared to beryl from other localities worldwide. Li+ substitution for Be2+ on the tetrahedral (T2) site is predominantly charge balanced by Na+ on the smaller channel (C2) site, with Na+ ranging from 91.5% to 99.7% (apfu) of the sum of all other alkali elements. Cs+ and minor Rb+ and K+ primarily charge balance the minor M2+ substitution for Al3+ at the A site; all iron at the A site is suggested to be trivalent. The a axis ranges from 9.2161(2) to 9.2171(4) Å, with unit-cell volume from 678.03(3) to 678.48(7) Å3. The c/a ratio of 1.0002–1.0005 is characteristic for T2-type beryl with unit-cell parameters controlled primarily by Be2+ substitution. Transmission micro-IR vibrational spectroscopy and imaging identifies coordination of one or two water molecules to Na+ (type IIs and type IId, respectively) as well as alkali free water (type I). Based on IR absorption cross section and XRD a C1 site water content of 0.4–0.5 apfu is derived, i.e. close to 50% site occupancy. Secondary crystal phases with a decrease in Fe and Mg, yet increase in Na, suggest early crystallisation of aquamarine, with goshenite being late. With similar crystal chemistry to beryl of columnar habit from other localities worldwide, the tabular habit of Xuebaoding beryl seems to be unrelated to chemical composition and alkali content.
Recent work in structure–processing relationships of polymer semiconductors have demonstrated the versatility and control of thin-film microstructure offered by meniscus-guided coating (MGC) techniques. Here, we analyze the qualitative and quantitative aspects of solution shearing, a model MGC method, using coating blades augmented with arrays of pillars. The pillars induce local regions of high strain rates—both shear and extensional—not otherwise possible with unmodified blades, and we use fluid mechanical simulations to model and study a variety of pillar spacings and densities. We then perform a statistical analysis of 130 simulation variables to find correlations with three dependent variables of interest: thin-film degree of crystallinity and transistor field-effect mobilities for charge-transport parallel (μpara) and perpendicular (μperp) to the coating direction. Our study suggests that simple fluid mechanical models can reproduce substantive correlations between the induced fluid flow and important performance metrics, providing a methodology for optimizing blade design.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
Titanium and its alloys are probably the most suitable materials for selective laser melting (SLM) additive manufacturing to process. However, the high cost of raw powder materials limits the industrial application of as-printed Ti products. In this study, we have formulated a cost-affordable Ti–TiB composite powder for SLM, to simultaneously achieve excellent mechanical performance and cost effectiveness. The optimization of the processing parameters will be shown to lead to high relative density (99.3%) for the as-printed Ti–TiB composites containing (0.5, 1, and 2 wt%) TiB2. Furthermore, by incorporating TiB2, the as-printed composites exhibit much improved fracture strength (up to 1813 MPa) and microhardness (up to 412 HV), among which the Ti–0.5 wt% TiB2 has demonstrated a great combination of strength (1007 and 1646 MPa as yield and fracture strengths, respectively) and tensile ductility (~8%). The solidification pathway for the Ti–TiB composite during SLM has been investigated, and the underlying mechanism for achieving high yield strength is discussed based on existing models for shear-lag strengthening, grain refinement, and dispersion strengthening.
Normal odd-chain SFA (OCSFA), particularly tridecanoic acid (n-13 : 0), pentadecanoic acid (n-15 : 0) and heptadecanoic acid (n-17 : 0), are normal components of dairy products, beef and seafood. The ratio of n-15 : 0:n-17 : 0 in ruminant foods (dairy products and beef) is 2:1, while in seafood and human tissues it is 1:2, and their appearance in plasma is often used as a marker for ruminant fat intake. Human elongases encoded by elongation of very long-chain fatty acid (ELOVL)1, ELOVL3, ELOVL6 and ELOVL7 catalyse biosynthesis of the dominant even-chain SFA; however, there are no reports of elongase function on OCSFA. ELOVL transfected MCF7 cells were treated with n-13 : 0, n-15 : 0 or n-17 : 0 (80 µm) and products analysed. ELOVL6 catalysed elongation of n-13 : 0→n-15 : 0 and n-15 : 0→n-17 : 0; and ELOVL7 had modest activity toward n-15 : 0 (n-15 : 0→n-17 : 0). No elongation activity was detected for n-17 : 0→n-19 : 0. Our data expand ELOVL specificity to OCSFA, providing the first molecular evidence demonstrating ELOVL6 as the major elongase acting on OCSFA n-13 : 0 and n-15 : 0 fatty acids. Studies of food intake relying on OCSFA as a biomarker should consider endogenous human metabolism when relying on OCSFA ratios to indicate specific food intake.
The cost-effectiveness of endovascular therapy (EVT) compared to tissue plasminogen activator (tPA) alone for acute ischemic stroke (AIS) has been established in the literature. However, decision-makers still face challenges of how to best deliver EVT in a timely manner to maximize patient outcomes while minimizing the burden to the healthcare system, given that AIS has time-dependent treatment outcomes. The objective of this presentation is to report an optimization approach for improving health system value and outcomes for patients with AIS who are eligible for EVT in Alberta.
Methods:
An economic model was developed to compare combinations of “mothership” (transport directly to a comprehensive stroke center [CSC] to receive tPA and EVT) and “drip-and-ship” (transport to a primary stroke centre to receive tPA, followed by transport to a CSC to receive EVT) methods across Alberta. The model considered geographical variation and searched for the best delivery methods through a pairwise comparison of all possible strategies. The controlled variables including in the model were population densities, disease epidemiology, time/distance to hospitals, available medical services, treatment eligibility and efficacy, and costs. Patient outcomes were measured by functional independence. The model defined optimal strategies by identifying the transport methods that produced the highest probability of improved health outcomes at the lowest cost.
Results:
The analysis produced an optimization map showing optimal strategies for EVT delivery. The lifetime cost (standard deviation [SD]) per patient and likelihood (SD) of good outcomes was CAD 291,769 (CAD 11,576) [USD 226,207 (USD 8,975)] and 41.82 percent (0.013) when considering optimal clinical outcomes, and CAD 287,725 (CAD 4,141) [USD 223,097 (USD 3,211)] and 41.67 percent (0.016) when considering optimal economic efficiency.
Conclusions:
Our model reduces the gap that exists between health technology implementation and cost-effectiveness analysis; namely, neither fully addresses relative efficiency driven by geographical variation, which may misrepresent system value in local settings. Implementation strategies generated in our model capture full values in terms of patient outcomes and costs.
OBJECTIVES/SPECIFIC AIMS: Precise biomarkers are urgently needed to characterize the tumor immune microenvironment in primary melanoma tumors both for prognostication and to predict the benefit of immuno-therapeutic intervention. The goal of this work is to define spatial relationships between CD8+ T cells, CD68+ macrophages and Sox10+ melanoma cells in order to define features correlating with prolonged survival METHODS/STUDY POPULATION: Five micrometer slides from either the primary biopsy or subsequent wide local excision procedure were stained using Opal multiplex IHC for DAPI, CD3 (LN10, Leica), CD8 (4B11, Leica), CD68 (KP1, Biogenex), SOX10 (BC34, Biocare), HLA-DR (LN-3, Abcam), and Ki67 (MIB1, Abcam). Cell phenotypes within representative fields preselected by a trained dermato-pathologist and were visualized using the Mantra quantitative pathology workstation (PerkinElmer), and analysis of spatial distribution of CD3+ CD8+ cells analyzed using inForm® image analysis software (PerkinElmer), and Spotfire software (TIBCO). In order to test whether mIHC can better characterize the tumor immune microenvironment, we screened databases at the Herbert Irving Cancer Center (HICC) at Columbia University for stage II/III melanoma patients diagnosed between 2000 and 2012, with available FFPE of primary melanoma tissue and documented clinical follow-up. We identified a preliminary population of 57 patients to begin our analysis. Clinical follow-up was available on 35 patients of whom 21 patients were alive with no evidence of recurrence or died with no evidence of recurrence and 14 had died of melanoma. Twenty-four patients had more than 24 months of survival information available but no detailed clinical information to determine cause of death. RESULTS/ANTICIPATED RESULTS: First, we evaluated whether density of immune cells in tumor and stroma predicted prognosis in 35 patients with disease specific survival information. We find that high number of CD3+CD8+ cells in tumor correlates with Disease Specific Survival (DSS) (p=0.0323*) and CD3+CD8+ cells in stroma may also correlate with DSS (p=0.0671). This is consistent with what is known in the literature regarding tumor infiltrating lymphocytes (TILs). We also found that CD68+ cells in stroma predict poor prognosis (0.0259*). This is consist with the proposed deleterious role for macrophages in tumor progression. Next, using nearest neighbor analysis we examined the effect of HLA-DR and Ki67 expression on spatial distribution of CD3+CD8+ T cells. We find that CD8+ T cells are closer to myeloid (CD68+) cells expressing HLA-DR. This is consistent with the potential of HLA-DR expressing cells to present antigens to T cells, and suggests that T cells may preferentially interact with HLA-DR expressing myeloid cells. Conversely, we find that Ki67 expression on tumor (SOX10+) cells correlates with increased distance from CD3+CD8+ T cells relative to SOX10+Ki67-tumor cells. This finding is consistent with the observation that more advanced tumors with higher mitotic rates have decreased T cell infiltrates, and suggests that dividing melanoma cells are less likely to interact with T cells. In addition, we performed analysis to determine whether spatial relationships defined above impact prognosis. Clinical oncology follow-up was available on 35 of the 57 patients evaluated above. We compared proximity of CD3+CD8+ cells to both myeloid (CD68+) and tumor (SOX10+) cells in patients who recurred and those with no evidence of recurrence. We found that CD3+CD8+ cells in patients who had recurrence were closer to CD68+ HLA-DR− cells than in patients who had no recurrence (t-test, p=0.0377), this correlated with DSS (p=0.003). Conversely, distance from CD3+CD8+ to CD68+ HLA-DR+ in relationship to recurrence was not significant with a trend towards CD3+CD8+ T cells being closer in nonrecurrent patients (t-test, p=0.1362). DISCUSSION/SIGNIFICANCE OF IMPACT: Consistent with the literature, we find that densities of CD8+ T cells correlates with favorable outcomes in early stage melanoma. We also find that density of CD68+ macrophages in stroma correlates with poor outcome. If proximity is a surrogate for interaction, these data indicate that dividing, Ki67+, melanoma cells interact less with CD8+ T cells than do Ki67+ melanoma cells. Further, HLA-DR expression on CD68+ infiltrating cells likely enhances their interaction with T cells. Interestingly, on further analysis, CD3+CD8+ cells were significantly closer to CD68+ HLA-DR− cells in patients who recurred, implying that interactions between these cell types may not be favorable. This analysis demonstrates that spatial analysis may be useful in predicting prognosis in early stage melanoma, and this is the first report of this type of analysis predicting outcomes in primary tumor specimens to our knowledge. Further staining and analysis of the complete patient cohort (n=120) is ongoing.
DNA nanostructures are a set of materials with well-defined physical, chemical, and biological properties that can be used on their own or incorporated with other materials for many applications. Herein, the practical aspects of utilizing DNA nanostructures (structural or dynamic) as materials are comprehensively covered. This article first summarizes properties of DNA molecules and practical considerations and then discusses the fundamental design principles of structural DNA nanostructures. Finally, various aspects of dynamic DNA nanostructure-based actuation and computation are included.
The large prehistoric city of Liangzhu and its associated earthen dike emerged on the Yangtze delta-coast after two millennia of occupation in this area by scattered communities. Details of its development have been widely discussed in the literature. Our results reveal that the city was selectively built at the head of an embayment backed by hills, with close access to food, freshwater and timber, and with protection from coastal hazards. Radiocarbon and optically stimulated luminescence (OSL) dating shows that it was built around 4.8–4.5 ka, and the earthen dike was constructed a little later at ~ 4.1 ka. During this time, saltwater wetlands were changing to freshwater in response to rapid coastal progradation as the postglacial sea-level rise stabilized. This facilitated rice farming and furthered the development of the city with elaborate city planning. The younger large-scale earthen dike and artificial ponds possibly suggest increasing demand for flood mitigation and irrigation.
Whether genetic factors influence the associations of fatty acids with the risk of sudden cardiac arrest (SCA) is largely unknown. To investigate possible gene–fatty acid interactions on SCA risk, we used a case-only approach and measured fatty acids in erythrocyte samples from 1869 SCA cases in a population-based repository with genetic data. We selected 191 SNP in ENCODE-identified regulatory regions of fifty-five candidate genes in fatty acid metabolic pathways. Using linear regression and additive genetic models, we investigated the association of the selected SNP with erythrocyte levels of fatty acids, including DHA, EPA and trans-fatty acids among the SCA cases. The assumption of no association in non-cases was supported by analysis of publicly available datasets containing over 8000 samples. None of the SNP–fatty acid associations tested among the cases reached statistical significance after correction for multiple comparisons. One SNP, rs4654990 near PLA2G2A, with an allele frequency of 0·33, was nominally associated with lower levels of DHA and EPA and higher levels of trans-fatty acids. The strongest association was with DHA levels (exponentiated coefficient for one unit (1 % of total fatty acids), 0·90, 95 % CI 0·85, 0·97; P = 0·003), indicating that for subjects with a coded allele, the OR of SCA associated with one unit higher DHA is about 90 % what it is for subjects with one fewer coded allele. These findings suggest that the associations of circulating n-3 and trans-fatty acids with SCA risk may be more pronounced in carriers of the rs4654990 G allele.
Both physical activity (PA) and diet are important contributors to health and well-being; however, there is limited information on the association of these behaviours and whether observed associations differ by weight. The present study aimed to evaluate whether nutrient intake is associated with PA and if this association varies by weight in young adults.
Design
Cross-sectional study to analyse the association between PA and nutrient intake.
Setting
Participants were stratified as normal weight (18·5 kg/m2 <BMI <25·0 kg/m2) and overweight/obese (BMI≥25·0 kg/m2). PA level (PAL) was calculated (PAL=total daily energy expenditure/RMR) and used to stratify groups (PAL<1·6, 1·6≤PAL<1·9, PAL≥1·9).
Subjects
Adults (n 407; age 27·6 (sd 3·8) years, 48 % male), with BMI between 20 and 35 kg/m2, having at least two 24 h diet recalls and at least 5 d (including two weekend days) of valid, objectively measured PA data were included in the analysis.
Results
In normal-weight participants, higher PAL was associated with higher intakes of minerals (except Ca, Fe and Zn), B-vitamins and choline (P for trend <0·05). In the overweight/obese group, higher PAL was associated with higher intakes of fibre, K, Na and Cu (P for trend <0·05). These differences, however, were no longer significant after additionally controlling for total energy intake.
Conclusions
More active young adults have higher intakes of essential micronutrients. The benefits of PA may be predominantly due to a higher overall food intake while maintaining energy balance rather than a healthier diet.
It is difficult to detect a stationary object in practice, especially in an unknown indoor environment, because (a) there is no distinct speed difference between the targets and the background; (b) responses of the targets are contaminated by dense unknown clutter; (c) a priori knowledge of the background is not always available for some scenarios. In this paper, a set of ultra-wideband sensors are used to detect a stationary target with a planar diffuse surface. It is shown that, the relative spectrum-shifts of the data after data-projection operation, are closely connected to the illumination-angle differences. Based on this, a detector is designed, and the location and the orientation of the target are determined. In order to mitigate the influence of clutters, a “time-shift & accumulation” scheme is designed to enhance the signal. As a consequence, the signal-to-interference-and-noise ratio is increased. In addition, results from measurement in a realistic indoor environment are provided.