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Stenting treatments for the management of disease in the heart, arterial and venous systems, biliary ducts, urethras, ureters, oesophageal tract and prostate have made enormous technical advances since their introduction into clinical use. The progression from metallic to polymer based bio-absorbable stents, coupled with the advances in additive manufacturing techniques, present a unique opportunity to completely re-envision the design, manufacture, and supply chain of stents. This paper looks at current stenting trends and proposes a future where the stent supply chain is condensed from ~150 days to ~20 min. The Cardiologist therefore has the opportunity to become a designer, manufacturer and user with patients receiving custom stents specific to their unique pathology that will be generated, delivered and deployed in the Cath-lab. The paper will outline this potentially revolutionary development and consider the technical challenges that will need to be overcome in order to achieve these ambitious goals. A high level overview of the generating eluting stents in situ program—GENESIS—is outlined including some early experimental work.

The computation of discrete polynomial transforms is a fundamental operation in the applied mathematical sciences. Much effort has been placed on the development of fast polynomial transforms, particularly those based on the fast Fourier transform. Two exact fast transform models of particular importance are the polynomial division tree model and the three-term recurrence rule model. Recent work has introduced some new fast polynomial transforms based on the two models. These algorithms have complexity at most$O(N \\log\\sp2 N)$ , as compared to the$O(N\\sp2$ ) direct methods; however, in some cases they display numerical instability on reasonable inputs. This thesis presents some heuristics which greatly improve the numerical reliability without sacrificing efficiency in either the asymptotic or execution time sense. For the fast transforms based on polynomial division, a heuristic technique called symmetry stabilization greatly improves the numerical reliability for the case where the sample points are on the unit circle. This technique improves the numerical reliability for three sample point distributions which arise in important applications with little or no increase in the complexity. New fast transforms based on the polynomial division model are described for generalized Chebyshev polynomials, which may also benefit from the symmetry stabilization technique. This new transform unifies the fast Fourier transform and the fast cosine transform as a single algorithm parameterized by a variable$\\rho\\ \\in$(0, 1). For the fast transforms based on three-term recurrence relations, a modified algorithm is described which uses stability bypass operations to improve the numerical reliability. This method has been tested extensively for transforms onto sets of associated Legendre functions, or fast Legendre transforms. The fast Legendre transform is used to effect a fast spherical harmonic transform on the 2-sphere, thereby giving an$O(N \\log\\sp2 N$ ) algorithm for convolving two functions on the sphere. Some efficient variations of the algorithm are described which are based on a \"semi-naive\" approach. Finally, a leveled hypercube parallel algorithm for the fast Legendre transform is described which is work optimal, and when used in conjunction with well-known parallel FFT algorithms, effects a work-optimal parallel algorithm for fast spherical harmonic transforms.

Japanese encephalitis virus (JEV) is a major cause of neurological disability in Asia and causes thousands of severe encephalitis cases and deaths each year. Although Japanese encephalitis (JE) is a WHO reportable disease, cases and deaths are significantly underreported and the true burden of the disease is not well understood in most endemic countries. Here, we first conducted a spatial analysis of the risk factors associated with JE to identify the areas suitable for sustained JEV transmission and the size of the population living in at-risk areas. We then estimated the force of infection (FOI) for JE-endemic countries from age-specific incidence data. Estimates of the susceptible population size and the current FOI were then used to estimate the JE burden from 2010 to 2019, as well as the impact of vaccination. Overall, 1,543.1 million (range: 1,292.6-2,019.9 million) people were estimated to live in areas suitable for endemic JEV transmission, which represents only 37.7% (range: 31.6-53.5%) of the over four billion people living in countries with endemic JEV transmission. Based on the baseline number of people at risk of infection, there were an estimated 56,847 (95% CI: 18,003-184,525) JE cases and 20,642 (95% CI: 2,252-77,204) deaths in 2019. Estimated incidence declined from 81,258 (95% CI: 25,437-273,640) cases and 29,520 (95% CI: 3,334-112,498) deaths in 2010, largely due to increases in vaccination coverage which have prevented an estimated 314,793 (95% CI: 94,566-1,049,645) cases and 114,946 (95% CI: 11,421-431,224) deaths over the past decade. India had the largest estimated JE burden in 2019, followed by Bangladesh and China. From 2010-2019, we estimate that vaccination had the largest absolute impact in China, with 204,734 (95% CI: 74,419-664,871) cases and 74,893 (95% CI: 8,989-286,239) deaths prevented, while Taiwan (91.2%) and Malaysia (80.1%) had the largest percent reductions in JE burden due to vaccination. Our estimates of the size of at-risk populations and current JE incidence highlight countries where increasing vaccination coverage could have the largest impact on reducing their JE burden.

By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during its initial invasion of the United States remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the United States through 12 March, we estimated that 108,689 (95% posterior predictive interval [95%PPI]: 1,023 to 14,182,310) infections occurred in the United States by this date. By comparing the model’s predictions of symptomatic infections with local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between 24 February and 12 March, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.98; 95% PPI: 0.66 to 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the United States.

Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538–146 505) were reported per year. 4·0% (95% CrI 1·7–16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes. The Bill & Melinda Gates Foundation.

Thaumatotibia leucotreta, known as the false codling moth, is a pest of citrus and other crops in sub-Saharan Africa. As it is endemic to this region and as South Africa exports most of its citrus around the world, T. leucotreta has phytosanitary status for most markets. This means that there is zero tolerance for any infestation with live larvae in the market. Consequently, control measures prior to exporting must be exemplary. Certain markets require a standalone postharvest disinfestation treatment for T. leucotreta. However, the European Union accepts a systems approach, consisting of three measures and numerous components within these measures. Although effective preharvest control measures are important under all circumstances, they are most critical where a standalone postharvest disinfestation treatment is not applied, such as within a systems approach. Conventional wisdom may lead a belief that effective chemical control tools are imperative to achieve this end. However, we demonstrate that it is possible to effectively control T. leucotreta to a level acceptable for a phytosanitary market, using only biological control tools. This includes parasitoids, predators, microbial control, semiochemicals, and sterile insects. Simultaneously, on-farm and environmental safety is improved and compliance with the increasing stringency of chemical residue requirements imposed by markets is achieved.

Large model uncertainty in projected future soil carbon (C) dynamics has been well documented. However, our understanding of the sources of this uncertainty is limited. Here we quantify the uncertainties arising from model parameters, structures and their interactions, and how those uncertainties propagate through different models to projections of future soil carbon stocks. Both the vertically resolved model and the microbial explicit model project much greater uncertainties to climate change than the conventional soil C model, with both positive and negative C-climate feedbacks, whereas the conventional model consistently predicts positive soil C-climate feedback. Our findings suggest that diverse model structures are necessary to increase confidence in soil C projection. However, the larger uncertainty in the complex models also suggests that we need to strike a balance between model complexity and the need to include diverse model structures in order to forecast soil C dynamics with high confidence and low uncertainty. A substantial portion of model uncertainty arises from model parameters and structures. Here, the authors show that alternative model structures with data-driven parameters project greater uncertainty in soil carbon responses to climate change than the conventional soil carbon model.

The polymerase chain reaction (PCR) has been used to amplify specific gene regions for many taxonomic studies and there have been substantial efforts to develop protocols that efficiently amplify target regions from a majority of mixed-template populations. Most protocols include the use of degenerate oligonucleotide primer pools, which contain mixed nucleotide sequences to improve priming from templates containing non-consensus sequence variations in their primer-binding sites. In this work, computational modeling and experimental measurements revealed that degenerate primers reduce efficiency well before a substantial product pool has been generated. It was also discovered that non-degenerate primers produced amplicons significantly better than their degenerate counterparts when amplifying either a consensus or a non-consensus target. Using quantitative, real-time PCR (qPCR) and data fitting as a guide, a new PCR protocol was developed that avoids the use of degenerate primers and allows for the stable amplification of targets containing mismatches to the targeting primers. This protocol involves the use of only two non-degenerate primers with no intermediate processing steps and it allows for the reproducible production of amplicon sequencing libraries that maintain the fractional representations of rare members.

Introduction: When analyzing data from large-scale genetic association studies, such as targeted or genome-wide resequencing studies, it is common to assume a single genetic model, such as dominant or additive, for all tests of association between a given genetic variant and the phenotype. However, for many variants, the chosen model will result in poor model fit and may lack statistical power due to model misspecification. Objective: We develop power and sample size calculations for tests of gene and gene × environment interaction, allowing for misspecification of the true mode of genetic susceptibility. Methods: The power calculations are based on a likelihood ratio test framework and are implemented in an open-source R package (“genpwr”). Results: We use these methods to develop an analysis plan for a resequencing study in idiopathic pulmonary fibrosis and show that using a 2-degree of freedom test can increase power to detect recessive genetic effects while maintaining power to detect dominant and additive effects. Conclusions: Understanding the impact of model misspecification can aid in study design and developing analysis plans that maximize power to detect a range of true underlying genetic effects. In particular, these calculations help identify when a multiple degree of freedom test or other robust test of association may be advantageous.

Structure–property relationships of an additively manufactured 316L stainless steel were explored. A scanning electron microscope and electron backscattered diffraction (EBSD) analysis revealed a fine cellular-dendritic (0.5 to 2 μm) substructure inside large irregularly shaped grains (~ 100 μm). The cellular structure grows along the 〈100〉 crystallographic directions. However, texture analysis revealed that the main 〈100〉 texture component is inclined by ~15 deg from the building direction. X-ray diffraction line profile analysis indicated a high dislocation density of ~1 × 1015 m−2 in the as-built material, which correlates well with the observed EBSD microstructure and high-yield strength, via the traditional Taylor hardening equation. Significant variations in strain hardening behavior and ductility were observed for the horizontal (HB) and vertical (VB) built samples. Ductility of HB and VB samples measured 49 and 77 pct, respectively. The initial growth texture and subsequent texture evolution during tensile deformation are held responsible for the observed anisotropy. Notably, EBSD analysis of deformed samples showed deformation twins, which predominately form in the grains with 〈111〉 aligned parallel to the loading direction. The VB samples showed higher twinning activity, higher strain hardening rates at high strain, and therefore, higher ductility. Analysis of annealed samples revealed that the observed microstructures and properties are thermally stable, with only a moderate decrease in strength and very similar levels of ductility and anisotropy, compared with the as-built condition.