The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.

It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.

The relationship of Aspicilia uxoris within Megasporaceae is assessed within a phylogenetic context. ‘Aspicilia’ uxoris and other related species are recovered as sister to the genus Lobothallia s. str. and described here as a new genus. Teuvoa (Ascomycota, Megasporaceae) is erected based on nuclear ITS and LSU sequence data and morphological characters. In addition to Teuvoa uxoris, a second species, T. junipericola, is added to the new genus based on material collected from North America. Teuvoa junipericola, T. uxoris and T. tibetica form a group with 8-spored asci, absence of extrolites, rather short-sized conidia and ascospores, lack of a subhypothecial algal layer, and different substratum preferences (on organic substratum) with a sister relationship to genus Lobothallia s. lat. (Aspicilia subgenus Pachyothallia Clauzade & C. Roux). Based on spore measurements of the holotypes, Lecanora ferganensis Tomin from central Asia (Kyrgyzstan, Tajikistan and Uzbekistan), Lecanora atrodiscata Gintovt, from Tajikistan and Lecanora takyroides Dzhur. from Turkmenistan are new synonyms to T. uxoris. A lectotype for Lecanora ferganensis is designated, expanding the known distribution of T. uxoris from Algeria, Morocco and Spain, into Central Asia.

Objectives: The Weight Loss Maintenance Trial (WLM) was a multicenter, randomized trial comparing two weight loss maintenance interventions, a personal contact (PC) program with primarily telephone-based monthly contacts, and an Internet-based program (interactive technology, IT), to a self-directed control group, among overweight or obese individuals at high cardiovascular risk. This study describes implementation costs of both interventions as well as IT development costs.

Methods: Resources were micro-costed in 2006 dollars from the primary perspective of a sponsoring healthcare system considering adopting an extant intervention, rather than developing its own. Costs were discounted at 3 percent annually. Length of trial participation was 30 months (randomization during February–November 2004). IT development costs were assessed over 36 months. Univariate and multivariate, including probabilistic, sensitivity analyses were performed.

Results: Total discounted IT development costs over 36 months were $839,949 ($2,414 per IT participant). Discounted 30-month implementation costs for 342 PC participants were $537,242 ($1,571 per participant), and for 348 IT participants, were $214,879 ($617 per participant). Under all plausible scenarios, PC implementation costs exceeded IT implementation costs.

Conclusions: Costs of implementing and operating an Internet-based intervention for weight loss maintenance were substantially less than analogous costs of an intervention using standard phone and in-person contacts and are of a magnitude that would be attractive to many health systems, subject to demonstration of cost-effectiveness.