In this review we describe fundamentals of scanning near-field optical microscopy with aperture probes. After the discussion of instrumentation and probe fabrication, aspects of light propagation in metal-coated, tapered optical fibers are considered. This includes transmission properties and field distributions in the vicinity of subwavelength apertures. Furthermore, the near-field optical image formation mechanism is analyzed with special emphasis on potential sources of artifacts. To underline the prospects of the technique, selected applications including amplitude and phase contrast imaging, fluorescence imaging, and Raman spectroscopy, as well as near-field optical desorption, are presented. These examples demonstrate that scanning near-field optical microscopy is no longer an exotic method but has matured into a valuable tool.

The absorption dipole orientation of single fluorescent molecules is determined by mapping the spatial distribution of the squared electric field components in a high-numerical-aperture laser focus. Annular illumination geometry and the vicinity of a plane dielectric/air interface strongly enhance the longitudinal field component and the transverse fields perpendicular to the polarization direction. As a result, all three excitation field components in the focus are of comparable magnitude. The scheme holds promise to monitor rotational diffusion of single molecules in complex environments.

A method called tube etching for the fabrication of near-field optical probes is presented. Tip formation occurs inside a cylindrical cavity formed by the polymer coating of an optical fiber which is not stripped away prior to etching in hydrofluoric acid. The influence of temperature, etchant concentration, and fiber type on the tip quality is studied. A tip formation mechanism for the given geometry is proposed. The procedure overcomes drawbacks of the conventional etching techniques while still producing large cone angles: (i) tips with reproducible shapes are formed in a high yield, (ii) the surface roughness on the taper is drastically reduced, and (iii) the tip quality is insensitive to vibrations and temperature fluctuations during the etching process. After aluminum coating, optical probes with well-defined apertures are obtained. Due to the smooth glass surface the aluminum coating is virtually free of pinholes.

; for the the Swiss EPO Neuroprotection Trial Group IMPORTANCE Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies. OBJECTIVE To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age. DESIGN, SETTING, AND PARTICIPANTS Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014. INTERVENTIONS Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. MAIN OUTCOMES AND MEASURES Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters. RESULTS Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, −1.0 [95% CI, −4.5 to 2.5]; P = .56). No differences were found between groups in the secondary outcomes. CONCLUSIONS AND RELEVANCE Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required.

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