Caustics and wavefronts produced by multiple refraction-reflections through plane-parallel plates.

We study the formation of caustics and wavefronts produced by multiple refraction-reflections through a plane-parallel transparent plate, assuming a point source placed at an arbitrary position along the optical axis. The caustic surfaces are obtained by using the envelope's method. Subsequently, the wavefronts are directly related to the involutes, which are associated with the envelopes for all the rays. Hence by using the Malus-Dupin theorem, we obtain their respective wavefronts produced by multiple refraction-reflections through a plane-parallel transparent plate. On the other hand, we implement Huygens' principle to obtain the wavefronts leaving the plate after undergoing multiple reflections inside the plate, which we have called zero-distance phase wavefronts. Finally, we establish the correspondence between the wavefronts obtained by Huygens' principle and the involutes associated with caustic surfaces; they are brought in coincidence assuming parallel curves from each other.

Management of Specific Clinical Profiles in Axial Spondyloarthritis: An Expert's Document Based on a Systematic Literature Review and Extended Delphi Process.

INTRODUCTION: The management of specific clinical scenarios is not adequately addressed in national and international guidelines for axial spondyloarthritis (axSpA). Expert opinions could serve as a valuable complement to these documents. METHODS: Seven expert rheumatologists identified controversial areas or gaps of current recommendations for the management of patients with axSpA. A systematic literature review (SLR) was performed to analyze the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs (csDMARDs, b/tsDMARDs) in axSpA regarding controversial areas or gaps. In a nominal group meeting, the results of the SLR were discussed and a set of statements were proposed. A Delphi process inviting 150 rheumatologists was followed to define the final statements. Agreement was defined as if at least 70% of the participants voted ≥ 7 (from 1, totally disagree, to 10, totally agree). RESULTS: Three overarching principles and 17 recommendations were generated. All reached agreement. According to them, axSpA care should be holistic and individualized, taking into account objective findings, comorbidities, and patients' opinions and preferences. Integrating imaging and clinical assessment with biomarker analysis could also help in decision-making. Connected to treatments, in refractory enthesitis, b/tsDMARDs are recommended. If active peripheral arthritis, csDMARD might be considered before b/tsDMARDs. The presence of significant structural damage, long disease duration, or HLA-B27-negative status do not contraindicate for the use of b/tsDMARDs. CONCLUSIONS: These recommendations are intended to complement guidelines by helping health professionals address and manage specific groups of patients, particular clinical scenarios, and gaps in axSpA.

Equations for designing a dialyte with minimal TSA based on the caustic surfaces.

A method to design a dialyte based on the caustic surfaces is presented, with correction at the third-order spherical aberration. We predefined, a priori, the value for the back focal length of the separated doublet for two different wavelengths to calculate their radii of curvature, which depend on all the parameters involved in the refraction process. Additionally, we approached the caustic surface by applying a Taylor series, which provided the analytical spherical aberration coefficient at the third order. Two alternatives to design achromatic separated doublets are provided. Finally, we extended the method to design achromatic cemented triplets.

Periodontal effects of maxillary expansion in adults using non-surgical expanders with skeletal anchorage vs. surgically assisted maxillary expansion: a systematic review.

OBJECTIVES: Describe and compare harmful periodontal effects as a consequence of maxillary expansion in adult patients with different types of anchorage devices in non-surgical expanders with skeletal anchorage and surgically assisted maxillary expansion. MATERIALS AND METHODS: An exhaustive search was carried out on the electronic databases PubMed (MEDLINE), Embase, Cochrane and LILACS. Additionally, journal references and grey literature were searched without any restrictions. After the selection and extraction process; risk of bias was assessed by the ROB-1 Cochrane tool and Newcastle-Ottawa Scale (NOS) for randomized trials and cohort studies, respectively. RESULTS: Of 621 studies retrieved from the searches, six were finally included in this review. One of them presented a low risk bias, while five were excellent respective to selection, comparability and outcomes. Results showed that maxillary expansion in adults using non-surgical expanders (bone-borne or tooth-bone-borne with bicortical skeletal anchorage) produce less harmful periodontal effects, such as: alveolar bending with an average range from 0.92° to 2.32°, compared to surgically assisted maxillary expansion (tooth-borne) of 6.4°; dental inclination with an average range from 0.07° to 2.4°, compared to surgically assisted maxillary expansion (tooth-borne) with a range from 2.01° to 5.56°. CONCLUSIONS: Although limited, the current evidence seems to show that the bone-borne or tooth-bone-borne with bicortical skeletal anchorage produces fewer undesirable periodontal effects.

Mechanically-Induced Long-Period Fiber Gratings Using Laminated Plates.

This work presents a formation method of mechanically-induced long-period fiber gratings using laminated plates. The mechanically-induced long-period fiber grating is temporarily inscribed by compressing the optical fiber between a flat plate and the proposed laminated plate. In turn, the new laminated plate consists of a parallel assembling of single-edged utility blades. We present the experimental characterization of mechanically-induced long-period fiber gratings while employing three laminated plates with a period of 480 ± 20 µm and low duty cycles. These mechanically-induced long-period fiber gratings display a leading rejection band (>15 dB) with a couple of shallow rejection bands (<2 dB) in the range of 1100-1700 nm. This spectral behavior is due to the new mechanical fabrication process that is based on laminated plates that we have proposed, which consists of piling multiple blades with trapezoidal edges that are polished with different levels to obtain different duty-cycles. With the proposed method, we can obtain values of duty-cycles around 10%, much lower than those obtained using traditional methods. Additionally, with this new method, the required mechanical pressure to form the grating is remarkably reduced, which minimizes the probability of the optical fiber failure in the mechanically-induced long-period fiber gratings (MI-LPFGs). Moreover, the proposed mechanically-induced long-period fiber gratings with a single rejection band open the feasibility to implement coarse wavelength division multiplexing systems that are based on long-period fiber gratings.

Tumor-on-a-chip: a microfluidic model to study cell response to environmental gradients.

Limited blood supply and rapid tumor metabolism within solid tumors leads to nutrient starvation, waste product accumulation and the generation of pH gradients across the tumor mass. These environmental conditions modify multiple cellular functions, including metabolism, proliferation, and drug response. However, capturing the spatial metabolic and phenotypic heterogeneity of the tumor with classic in vitro models remains challenging. Thus, in this work a microfluidic tumor slice model was developed to study cell behavior under metabolic starvation gradients. The presented microdevice comprises a central chamber where tumor cells were cultured in a 3D collagen hydrogel. A lumen on the flank of the chamber was used to perfuse media, mimicking the vasculature. Under these circumstances, tumor cell metabolism led to the generation of viability, proliferation and pH gradients. The model decoupled the influence of oxygen from other nutrients, revealing that cell necrosis at the core of the model could be explained by nutrient starvation. The microdevice can be disassembled to retrieve the cells from the desired locations to study molecular adaptions due to nutrient starvation. When exposed to these pH gradients and low nutrient conditions, cancer cells showed multiple changes in their gene expression profile depending on their distance from the lumen. Those cells located further from the lumen upregulated several genes related to stress and survival response, whereas genes related to proliferation and DNA repair were downregulated. This model may help to identify new therapeutic opportunities to target the metabolic heterogeneity observed in solid tumors.

Economic Impact of Etanercept in Patients with Psoriasis and Psoriatic Arthritis in Spain: A Systematic Review.

INTRODUCTION: Etanercept (ETN), a highly effective biological agent for the treatment of psoriasis (PSO) and psoriatic arthritis (PsA), is widely used in Spain. However, evidence of its economic impact is limited, indicating the need for a systematic review of the economic assessments conducted on the use of ETN in the treatment of both PSO and PsA in Spain. METHODS: A systematic review was carried out in PubMed, Embase, Cochrane Library, Health Technology Assessment reports and not indexed sources up to November 2018. The inclusion criteria were economic evaluations (total and partial) and dose optimization studies published in English or Spanish on the use of ETN to treat PSO and PsA for ETN in Spain. RESULTS: A total of 402 publications were identified, of which 32 were selected for inclusion in the review; of these 32 publications, 81.3% analyzed PSO (14 full economic evaluations, 5 partial economic evaluations and 7 dose optimization studies) and 18.8% analyzed PsA (1 economic analysis and 5 dose optimization studies). The perspective of the Spanish National Health Service (NHS) was used in 90.0% (n = 18) of the full and partial economic evaluations. The time horizons ranged from 12 weeks to 2 years. Reductions in the Psoriasis Area and Severity Index (PASI) of 50, 75 and 90% (PASI 50, 75 and 90, respectively) were most commonly used as efficacy outcomes in the complete evaluations. The economic impact of ETN ranged from €9110-14,337/PASI 75 at 12 weeks (50 mg/week) to €82,279/PASI 90 at 2 years, depending on the health outcome, time horizon and ETN dose used. Only one study determined the cost of using ETN for the treatment of PSO (€29,430-52,367/QALY for dose 2 × 25 mg/week or 50 mg/week, respectively). Only one partial economic evaluation on PSA was identified (NHS perspective), resulting in an ETN annual cost of €8585/patient-year. CONCLUSION: Consistent evidence on the economic impact of ETN for the treatment of PSO and PSA in Spain is lacking, mainly due to the highly heterogeneous methodology used and the broad range of outcomes found in the economic evaluations published to date. FUNDING: Pfizer S.L.U.

Organotypic microfluidic breast cancer model reveals starvation-induced spatial-temporal metabolic adaptations.

BACKGROUND: Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer. During DCIS, tumor cells remain inside the mammary duct, growing under a microenvironment characterized by hypoxia, nutrient starvation, and waste product accumulation; this harsh microenvironment promotes genomic instability and eventually cell invasion. However, there is a lack of biomarkers to predict what patients will transition to a more invasive tumor or how DCIS cells manage to survive in this harsh microenvironment. METHODS: In this work, we have developed a microfluidic model that recapitulates the DCIS microenvironment. In the microdevice, a DCIS model cell line was grown inside a luminal mammary duct model, embedded in a 3D hydrogel with mammary fibroblasts. Cell behavior was monitored by confocal microscopy and optical metabolic imaging. Additionally, metabolite profile was studied by NMR whereas gene expression was analyzed by RT-qPCR. FINDINGS: DCIS cell metabolism led to hypoxia and nutrient starvation; revealing an altered metabolism focused on glycolysis and other hypoxia-associated pathways. In response to this starvation and hypoxia, DCIS cells modified the expression of multiple genes, and a gradient of different metabolic phenotypes was observed across the mammary duct model. These genetic changes observed in the model were in good agreement with patient genomic profiles; identifying multiple compounds targeting the affected pathways. In this context, the hypoxia-activated prodrug tirapazamine selectively destroyed hypoxic DCIS cells. INTERPRETATION: The results showed the capacity of the microfluidic model to mimic the DCIS structure, identifying multiple cellular adaptations to endure the hypoxia and nutrient starvation generated within the mammary duct. These findings may suggest new potential therapeutic directions to treat DCIS. In summary, given the lack of in vitro models to study DCIS, this microfluidic device holds great potential to find new DCIS predictors and therapies and translate them to the clinic.

Adhesion Enhancements and Surface-Enhanced Raman Scattering Activity of Ag and Ag@SiO2 Nanoparticle Decorated Ragweed Pollen Microparticle Sensor.

A simple solution processed layer-by-layer approach was used to immobilize metal nanoparticles (NPs) on the surface of ragweed pollen exine to obtain multifunctional particles with significant surface-enhanced Raman scattering (SERS), two-photon excited fluorescence, and enhanced adhesion properties. The rugged pollen exine was functionalized with an amine terminated silane and then treated with Ag or Ag@SiO2 NPs that were electrostatically attached to the exterior of the pollen by incubation in an NP solution of the appropriate pH. Nanoparticle agglomeration on the pollen gives rise to broadband near infrared (NIR) (785-1064 nm) plasmonic activity, and strong SERS signals from benzenedithiol deposited on NP-pollen composite particles were observed. In addition to SERS activity, the AgNP coating provides a twofold increase in the adhesive properties of the RW pollen exine on a silicon substrate, leading to a robust, adhesive, broadband NIR excitable SERS microparticle.

Modal interferometer based on a single mechanically induced long-period fiber grating and a nanoparticles-coated film section.

A modal interferometer by a single mechanically induced long-period fiber grating (MI-LPFG) using a half-length coating fiber is presented. The coating material used for this Letter is a film of silica nanoparticles doped with an organic chromophore. The silica nanoparticles, with diameters within the range of 40-50 nm, were deposited over 3.5 cm length of fiber by the dip-coating method, forming a film with a thickness between 500 and 1250 nm. Then the modal interferometer was implemented by inscribing the MI-LPFG over the coated fiber section and a similar fiber length of the uncoated fiber. The experimental results show high-contrast transmission bands, where the position and depth of the absorption envelope band are finely selected by the grating period, the pressure applied, and the film thickness. The novel modal interferometer architecture based on a single MI-LPFG, combined with a functionalized nanoparticles coating film, offers an attractive platform for the development of fiber sensors and other fiber-based devices.

Liquid Temperature Measurements Using Two Different Tunable Hollow Prisms.

This paper describes the design, fabrication, and testing of two hollow prisms. One is a prism with a grating glued to its hypotenuse. This ensemble, prism + grating, is called a grism. It can be applied as an on-axis tunable spectrometer. The other hollow prism is a constant deviation one called a Pellin-Broca. It can be used as a tunable dispersive element in a spectrometer with no moving parts. The application of prisms as temperature sensors is shown.

Pollenkitt wetting mechanism enables species-specific tunable pollen adhesion.

Plant pollens are microscopic particles exhibiting a remarkable breadth of complex solid surface features. In addition, many pollen grains are coated with a viscous liquid, "pollenkitt", thought to play important roles in pollen dispersion and adhesion. However, there exist no quantitative studies of the effects of solid surface features or pollenkitt on adhesion of pollen grains, and it remains unclear what role these features play in pollen adhesion and transport. We report AFM adhesion measurements of five pollen species with a series of test surfaces in which each pollen has a unique solid surface morphology and pollenkitt volume. The results indicate that the combination of surface morphology (size and shape of echinate or reticulate features) with the pollenkitt volume provides pollens with a remarkably tunable adhesion to surfaces. With pollenkitt removed, pollen grains had relatively low adhesion strengths that were independent of surface chemistry and scalable with the tip radius of the pollen's ornamentation features, according to the Hamaker model. With the pollenkitt intact, adhesion was up to 3-6 times higher than the dry grains and exhibited strong substrate dependence. The adhesion enhancing effect of pollenkitt was driven by the formation of pollenkitt capillary bridges and was surprisingly species-dependent, with echinate insect-pollinated species (dandelion and sunflower) showing significantly stronger adhesion and higher substrate dependence than wind-pollinated species (ragweed, poplar, and olive). The combination of high pollenkitt volume and large convex, spiny surface features in echinate entomophilous varieties appears to enhance the spreading area of the liquid pollenkitt relative to varieties of pollen with less pollenkitt volume and less pronounced surface features. Measurements of pollenkitt surface energy indicate that the adhesive strength of capillary bridges is primarily dependent on nonpolar van der Waals interactions, with some contribution from the Lewis basic component of surface energy.

Spatially resolved solid-state 1H NMR for evaluation of gradient-composition polymeric libraries.

Polyurethane libraries consisting of films with composition gradients of aliphatic polyisocyanate and hydroxy-terminated polyacrylate resin were characterized using methods of (1)H NMR microimaging (i.e., magnetic resonance imaging, (MRI)) and solid-state NMR. Molecular mobilities and underlying structural information were extracted as a function of the relative content of each of the two components. Routine NMR microimaging using the spin-echo sequence only allows investigations of transverse relaxation of magnetization at echo times >2 ms. A single-exponential decay was found, which is likely due to free, noncross-linked polymer chains. The mobility of these chains decreases with increasing content of the aliphatic polyisocyanate. The concept of a 1D NMR profiler is introduced as a novel modality for library screening, which allows the convenient measurement of static solid-state NMR spectra as a function of spatial location along a library sample that is repositioned in the rf coil between experiments. With this setup the complete transverse relaxation function was measured using Bloch decays and spin echoes. For all positions within the gradient-composition film, relaxation data consisted of at least three components that were attributed to a rigid highly cross-linked resin, an intermediate cross-linked but mobile constituent, and the highly mobile free polymer chains (the latter is also detectable by MRI). Analysis of this overall relaxation function measured via Bloch decays and spin echoes revealed only minor changes in the mobilities of the individual fractions. Findings with respect to the most mobile components are consistent with the results obtained by NMR microimaging. The major effect is the significant increase in the rigid-component fraction with the addition of the hydroxy-terminated polyacrylate resin.

An intrinsic fiber-optic single loop micro-displacement sensor.

A micro-displacement sensor consisting of a fiber-loop made with a tapered fiber is reported. The sensor operation is based on the interaction between the fundamental cladding mode propagating through the taper waist and higher order cladding modes excited when the taper is deformed to form a loop. As a result, a transmission spectrum with several notches is observed, where the notch wavelength resonances shift as a function of the loop diameter. The loop diameter is varied by the spatial displacement of one end of the fiber-loop attached to a linear translation stage. In a displacement range of 3.125 mm the maximum wavelength shift is 360.93 nm, with 0.116 nm/µm sensitivity. By using a 1,280 nm broadband low-power LED source and a single Ge-photodetector in a power transmission sensor setup, a sensitivity in the order of 2.7 nW/µm is obtained in ≈ 1 mm range. The proposed sensor is easy to implement and has a plenty of room to improve its performance.

Dye-labeled polystyrene latex microspheres prepared via a combined swelling-diffusion technique.

A series of water-insoluble, biologically compatible dyes, meso-tetraphenylchlorin, meso-tetraphenylporphyrin and chlorophyll-a, were successfully incorporated into beads composed of linear polystyrene (PS) via a tunable combined swelling-diffusion process. Dyed PS beads were prepared by the addition of a dye solution in tetrahydrofuran to an aqueous suspension of 10 µm PS beads in the presence of a poly((ethylene glycol)-b-(propylene glycol)-b-(ethylene glycol)) block copolymer surfactant. The presence of surfactant was found to be beneficial to prevent particle aggregation, especially at tetrahydrofuran contents above 30%. Dye loading was shown to be tunable by simple adjustments in dye composition. Confocal fluorescence microscopy indicated that dyes were distributed uniformly throughout the entire PS bead, but heterogeneously with ~500 nm diameter droplets, indicative of a separate dye phase within the PS matrix. The stability of dyed beads, indicated by resistance to dye leaching in solvent, was found to be governed by the degree of swelling of PS in the solvent medium. Hence, no leaching was observed even when a good solvent for the dye was used (ethanol), as long as that solvent did not swell the carrier particle, PS. No leaching of dyes from the beads was observed during long-term (2 years) storage in water.

Non-DLVO silica interaction forces in NMP-water mixtures. I. A symmetric system.

Despite the success of DLVO theory, there exist numerous examples of interactions that do not follow its predictions. One prominent example is the interaction between hydrophilic surfaces in mixtures of water with another polar, associating solvent. Interactions of such surfaces are still poorly understood yet play a key role in a wide variety of processes in nature, biology, and industry. The interaction forces between a silica sphere and a glass plate in N-methyl-2-pyrrolidone (NMP)-water binary mixtures were measured using the AFM technique. The interactions in pure NMP and pure water agreed qualitatively with DLVO theory. In contrast, the addition of NMP to water drastically altered the interactions, which no longer followed DLVO predictions. An unusually strong, long-range (50-80 nm), multistepped attractive force was observed on the approach of hydrophilic surfaces in the NMP concentration range of 30-50 vol %, where the adhesive pull-off force was also maximized. The maximum attractive force was observed at an NMP concentration near 30 vol %, consistent with the formation of a strong hydrogen-bonded complex between NMP and water near the solid surface. The analysis of force profiles, zeta potentials, solution viscosity, and contact angles suggests that attraction arises from the bridging of surface-adsorbed macrocluster layers known to form on hydrophilic surfaces in mixtures of associating liquids.