One-step direct-laser metal writing of sub-100 nm 3D silver nanostructures in a gelatin matrix.

Developing an ability to fabricate high-resolution, 3D metal nanostructures in a stretchable 3D matrix is a critical step to realizing novel optoelectronic devices such as tunable bulk metal-dielectric optical devices and THz metamaterial devices that are not feasible with alternative techniques. We report a new chemistry method to fabricate high-resolution, 3D silver nanostructures using a femtosecond-laser direct metal writing technique. Previously, only fabrication of 3D polymeric structures or single-/few-layer metal structures was possible. Our method takes advantage of unique gelatin properties to overcome such previous limitations as limited freedom in 3D material design and short sample lifetime. We fabricate more than 15 layers of 3D silver nanostructures with a resolution of less than 100 nm in a stable dielectric matrix that is flexible and has high large transparency that is well-matched for potential applications in the optical and THz metamaterial regimes. This is a single-step process that does not require any further processing. This work will be of interest to those interested in fabrication methods that utilize nonlinear light-matter interactions and the realization of future metamaterials.

The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study.

BACKGROUND: In general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature. OBJECTIVE: The primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments. METHODS: A retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (<6 months) were excluded to avoid situations that were more likely attributable to treatment initiation than inadequate therapeutic effect. Trained nurses extracted data from patient charts and electronic medical record systems for review. We analyzed the cost of resources consumed by the frequency of levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group). RESULTS: The study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this cohort, there was an 86.4% increase in lost productivity vs. patients who had no levothyroxine dose adjustments (US$1833 vs. US$984). CONCLUSIONS: Patients experiencing multiple levothyroxine dose adjustments were shown to consume more healthcare resources, resulting in higher costs than those who required no dose adjustments. Each care episode contributed to lost time and wages with total estimated lost productivity escalating with increasing levothyroxine dose adjustments over a 24-month period.

Comorbidities, Concomitant Medications, and Diet as Factors Affecting Levothyroxine Therapy: Results of the CONTROL Surveillance Project.

BACKGROUND: The CONTROL Surveillance Project was a comprehensive patient-based survey conducted among hypothyroid patients undergoing treatment. The primary objective of the study was to specifically quantify the prevalence of factors adversely affecting levothyroxine therapy. METHODS: Participants were selected from a large proprietary database. Those eligible for the study completed a 21-question survey. RESULTS: Of the eligible hypothyroid patients, 925 (92.5%) were being treated with levothyroxine monotherapy. The mean age was 60.4 years; 755 (81.6%) were female and 168 (18.2%) were male. Almost half of those receiving levothyroxine (435, 47.0%) had at least one comorbid condition that could adversely affect its absorption: gastroesophageal reflux disease (33.8% of patients), irritable bowel syndrome (9.7%), lactose intolerance (7.8%), or a history of gastric bypass surgery or bowel resection (3.0%). Other factors reported by many patients that could adversely affect levothyroxine absorption included use of prescription medications (20.6%) and over-the-counter medications (34.3%) used to treat comorbid gastrointestinal (GI) conditions; use of dietary supplements (51.8%, primarily calcium and iron); and intake of foods/beverages high in fiber, iodine, or soy (68.0%). Of the 13.4% who reported difficulty controlling their hypothyroid symptoms, significantly more patients with comorbid GI conditions reported such difficulty (7.8 versus 5.6%, P < 0.01). Frequent changes in levothyroxine dosing (two or more dose changes in the past year) were reported by 8.0% of survey participants. Those with GI comorbidities were nearly twice as likely to have such changes (5.0 versus 3.0%, P < 0.01). CONCLUSION: Better initial workup of patients, including identification of relevant GI comorbidities and allergies, may help in the early detection of factors that may affect the performance of levothyroxine.

A method to fabricate disconnected silver nanostructures in 3D.

The standard nanofabrication toolkit includes techniques primarily aimed at creating 2D patterns in dielectric media. Creating metal patterns on a submicron scale requires a combination of nanofabrication tools and several material processing steps. For example, steps to create planar metal structures using ultraviolet photolithography and electron-beam lithography can include sample exposure, sample development, metal deposition, and metal liftoff. To create 3D metal structures, the sequence is repeated multiple times. The complexity and difficulty of stacking and aligning multiple layers limits practical implementations of 3D metal structuring using standard nanofabrication tools. Femtosecond-laser direct-writing has emerged as a pre-eminent technique for 3D nanofabrication.(1,2) Femtosecond lasers are frequently used to create 3D patterns in polymers and glasses.(3-7) However, 3D metal direct-writing remains a challenge. Here, we describe a method to fabricate silver nanostructures embedded inside a polymer matrix using a femtosecond laser centered at 800 nm. The method enables the fabrication of patterns not feasible using other techniques, such as 3D arrays of disconnected silver voxels.(8) Disconnected 3D metal patterns are useful for metamaterials where unit cells are not in contact with each other,(9) such as coupled metal dot(10,11)or coupled metal rod(12,13) resonators. Potential applications include negative index metamaterials, invisibility cloaks, and perfect lenses. In femtosecond-laser direct-writing, the laser wavelength is chosen such that photons are not linearly absorbed in the target medium. When the laser pulse duration is compressed to the femtosecond time scale and the radiation is tightly focused inside the target, the extremely high intensity induces nonlinear absorption. Multiple photons are absorbed simultaneously to cause electronic transitions that lead to material modification within the focused region. Using this approach, one can form structures in the bulk of a material rather than on its surface. Most work on 3D direct metal writing has focused on creating self-supported metal structures.(14-16) The method described here yields sub-micrometer silver structures that do not need to be self-supported because they are embedded inside a matrix. A doped polymer matrix is prepared using a mixture of silver nitrate (AgNO3), polyvinylpyrrolidone (PVP) and water (H2O). Samples are then patterned by irradiation with an 11-MHz femtosecond laser producing 50-fs pulses. During irradiation, photoreduction of silver ions is induced through nonlinear absorption, creating an aggregate of silver nanoparticles in the focal region. Using this approach we create silver patterns embedded in a doped PVP matrix. Adding 3D translation of the sample extends the patterning to three dimensions.