Three-dimensional nanofabrication of silver structures in polymer with direct laser writing

This dissertation describes methodology that significantly improves the state of femtosecond laser writing of metals. The developments address two major shortcomings: poor material quality, and limited 3D patterning capabilities. In two dimensions, we grow monocrystalline silver prisms through femtosecond laser irradiation. We thus demonstrate the ability to create high quality material (with limited number of domains), unlike published reports of 2D structures composed of nanoparticle aggregates. This development has broader implications beyond metal writing, as it demonstrates a one-step fabrication process to localize bottom-up growth of high quality monocrystalline material on a substrate. In three dimensions, we direct laser write fully disconnected 3D silver structures in a polymer matrix. Since the silver structures are embedded in a stable matrix, they are not required to be self-supported, enabling the one-step fabrication of 3D patterns of 3D metal structures that need-not be connected. We demonstrate sub-100-nm silver structures. This latter development addresses a broader limitation in fabrication technologies, where 3D patterning of metal structures is difficult. We demonstrate several 3D silver patterns that cannot be obtained through any other fabrication technique known to us. We expect these advances to contribute to the development of new devices in optics, plasmonics, and metamaterials. With further improvements in the fabrication methods, the list of potential applications broadens to include electronics (e.g. 3D microelectronic circuits), chemistry (e.g. catalysis), and biology (e.g. plasmonic biosensing).Engineering and Applied Science

Patient Preferences of Low-Dose Aspirin for Cardiovascular Disease and Colorectal Cancer Prevention in Italy:A Latent Class Analysis

BACKGROUND: Patients taking low-dose aspirin to prevent cardiovascular disease (CVD) may also benefit from a reduced risk of colorectal cancer (CRC). OBJECTIVE: The aim was to examine the preferences of people eligible for preventive treatment with low-dose aspirin and the trade-offs they are willing to make between CVD prevention, CRC prevention, and treatment risks. METHODS: A cross-sectional study using a discrete choice experiment (DCE) survey was conducted in Italy in 2019 to elicit preferences for three benefit attributes (prevention of ischemic stroke, myocardial infarction, and CRC) and four risk attributes (intracranial and gastrointestinal bleeding, peptic ulcer, and severe allergic reaction) associated with use of low-dose aspirin. Latent class logit models were used to evaluate variation in treatment preferences. RESULTS: The DCE survey was completed by 1005 participants eligible for use of low-dose aspirin. A four-class model had the best fit for the primary CVD prevention group (n = 491), and a three-class model had the best fit for the secondary CVD prevention group (n = 514). For the primary CVD prevention group, where classes differed on age, education level, type 2 diabetes, exercise, and low-dose aspirin use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and CRC (one class). For the secondary CVD prevention group, where classes differed on various comorbidities, self-reported health, exercise, and CVD medication use, the most important attributes were intracranial bleeding (two classes), myocardial infarction (one class), and gastrointestinal bleeding (one class). CONCLUSION: Patient preferences for the benefits and risks of low-dose aspirin differ significantly among people eligible for treatment as primary or secondary CVD prevention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00506-2

Co-infections of Adenovirus Species in Previously Vaccinated Patients

Adenoviral infections associated with respiratory illness in military trainees involve multiple co-infecting species and serotypes

Application of Broad-Spectrum, Sequence-Based Pathogen Identification in an Urban Population

A broad spectrum detection platform that provides sequence level resolution of target regions would have a significant impact in public health, case management, and means of expanding our understanding of the etiology of diseases. A previously developed respiratory pathogen microarray (RPM v.1) demonstrated the capability of this platform for this purpose. This newly developed RPM v.1 was used to analyze 424 well-characterized nasal wash specimens from patients presenting with febrile respiratory illness in the Washington, D. C. metropolitan region. For each specimen, the RPM v.1 results were compared against composite reference assay (viral and bacterial culture and, where appropriate, RT-PCR/PCR) results. Across this panel, the RPM assay showed ≥98% overall agreement for all the organisms detected compared with reference methods. Additionally, the RPM v.1 results provide sequence information which allowed phylogenetic classification of circulating influenza A viruses in ∼250 clinical specimens, and allowed monitoring the genetic variation as well as antigenic variability prediction. Multiple pathogens (2–4) were detected in 58 specimens (13.7%) with notably increased abundances of respiratory colonizers (esp. S. pneumoniae) during viral infection. This first-ever comparison of a broad-spectrum viral and bacterial identification technology of this type against a large battery of conventional “gold standard” assays confirms the utility of the approach for both medical surveillance and investigations of complex etiologies of illness caused by respiratory co-infections

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701