Dynamic curvature sensing using time expanded ΦOTDR.

Shape sensing can be accomplished using optical fiber sensors through different interrogation principles such as fiber Bragg gratings, optical frequency-domain reflectometry (OFDR), or optical time-domain reflectometry (OTDR). These techniques are either not entirely distributed, have poor performance in dynamic sensing, or are only valid for few-meter-long fibers. Here, we present a system able to perform distributed curvature sensing with a range of 125 m, 10-cm resolution, and a sampling rate of 50 Hz. This is done by interrogating three cores of a multi-core fiber (MCF) with the novel, to the best of our knowledge, time-expanded phase-sensitive (TE-Φ)OTDR technique. This system fills a performance gap in fiber shape sensors, opening the door to applications in civil engineering, medicine, or seismology.

Analytical reference framework to analyze non-COVID-19 events.

BACKGROUND: The COVID-19 pandemic has disrupted the healthcare system, leading to delays in detection of other non-COVID-19 diseases. This paper presents ANE Framework (Analytics for Non-COVID-19 Events), a reliable and user-friendly analytical forecasting framework designed to predict the number of patients with non-COVID-19 diseases. Prior to 2020, there were analytical models focused on specific illnesses and contexts. Then, most models have focused on understanding COVID-19 behavior. There is a lack of analytical frameworks that enable disease forecasting for non-COVID-19 diseases. METHODS: The ANE Framework utilizes time series analysis to generate forecasting models. The framework leverages daily data from official government sources and employs SARIMA models to forecast the number of non-COVID-19 cases, such as tuberculosis and suicide attempts. RESULTS: The framework was tested on five different non-COVID-19 events. The framework performs well across all events, including tuberculosis and suicide attempts, with a Mean Absolute Percentage Error (MAPE) of up to 20% and the consistency remains independent of the behavior of each event. Moreover, a pairwise comparison of averages can lead to over or underestimation of the impact. The disruption caused by the pandemic resulted in a 17% gap (2383 cases) between expected and reported tuberculosis cases, and a 19% gap (2464 cases) for suicide attempts. These gaps varied between 20 and 64% across different cities and regions. The ANE Framework has proven to be reliable for analyzing several diseases and exhibits the flexibility to incorporate new data from various sources. Regular updates and the inclusion of new associated data enhance the framework's effectiveness. CONCLUSIONS: Current pandemic shows the necessity of developing flexible models to be adapted to different illness data. The framework developed proved to be reliable for the different diseases analyzed, presenting enough flexibility to update with new data or even include new data from different databases. To keep updated on the result of the project allows the inclusion of new data associated with it. Similarly, the proposed strategy in the ANE framework allows for improving the quality of the obtained results with news events.

Optical fiber point sensors based on forward Brillouin scattering.

Forward Brillouin scattering interactions support the sensing and analysis of media outside the cladding boundaries of standard fibers, where light cannot reach. Quantitative point-sensing based on this principle has yet to be reported. In this work, we report a forward Brillouin scattering point-sensor in a commercially available, off-the-shelf multi-core fiber. Pump light at the inner, on-axis core of the fiber is used to stimulate a guided acoustic mode of the entire fiber cross-section. The acoustic wave, in turn, induces photoelastic perturbations to the reflectivity of a Bragg grating inscribed in an outer, off-axis core of the same fiber. The measurements successfully analyze refractive index perturbations on the tenth decimal point and distinguish between ethanol and water outside the centimeter-long grating. The measured forward Brillouin scattering linewidths agree with predictions. The acquired spectra are unaffected by forward Brillouin scattering outside the grating region. The results add point-analysis to the portfolio of forward Brillouin scattering optical fiber sensors.

Polycystic ovarian syndrome: signs and feedback effects of hyperandrogenism and insulin resistance.

Polycystic ovary syndrome (PCOS) is a disease whose diagnosis is based on the detection of hyperandrogenism (HA) and ovulatory dysfunction. Women with PCOS frequently develop insulin resistance (IR), which generates a metabolic condition that involves a decrease in the action of insulin at the cellular level and is linked to compensatory hyperinsulinemia (HI). In PCOS, the ovary remains sensitive to the action of insulin. Additionally, it has been observed that the main effect of insulin in the ovary is the stimulation of androgen synthesis, resulting in HA, one of the fundamental characteristics of the PCOS. In this sense, the excess of androgens favors the development of IR, thus perpetuating the cycle of IR-HI-HA, and therefore PCOS. Moreover, mitochondrial dysfunction is present in PCOS patients and is a common feature in both IR and HA. This review places electron transfer as a key element in HA and IR development, with emphasis on the relationship between androgen biosynthesis and mitochondrial function. Indeed, metformin has been involved in repair mitochondrial dysfunction, decrease of oxidative stress, reduction of androgens levels and the enhancing of insulin sensitivity. Therefore, we propose that treatment with metformin could decrease HI and consequently HA, restoring, at least in part, the metabolic and hormonal disorders of PCOS.

Multicore optical fiber shape sensors suitable for use under gamma radiation.

We have designed and implemented a fiber optic shape sensor for high-energy ionizing environments based on multicore optical fibers. We inscribed two fiber Bragg gratings arrays in a seven-core optical fiber. One of the arrays has been inscribed in a hydrogen-loaded fiber and the other one in an unloaded fiber in order to have two samples with very different radiation sensitivity. The two samples were coiled in a metallic circular structure and were exposed to gamma radiation. We have analyzed the permanent radiation effects. The radiation-induced Bragg wavelength shift (RI-BWS) in the hydrogen-loaded fiber is near ten times higher than the one observed for the unloaded fiber, with a maximum wavelength shift of 415 pm. However, the use of the multiple cores permits to make these sensors immune to RI-BWS obtaining a similar curvature error in both samples of approximately 1 cm without modifying the composition of the fiber, pre-irradiation or thermal treatment.

Sampled true time delay line operation by inscription of long period gratings in few-mode fibers.

We propose and experimentally demonstrate distributed microwave photonics signal processing over a few-mode fiber link by implementing 4-sample true time delay line operation. The inscription of a set of long period gratings at specific locations along the few-mode fiber allows the excitation of the higher-order modes while adjusting the individual sample group delays and amplitudes that are required for sampled true time delay line behavior. Since solely the injection of the fundamental mode at the few-mode fiber input is required, we render this signal processing system independent of any preceding fiber link that may be required in addition to distribute the signal. We experimentally validate the performance of the implemented true time delay line when applied to radiofrequency signal filtering.

Steroid hormones and pregnancy.

Pregnancy is associated with physiological adjustments in order to allow adequate growth and fetal development. In particular, steroids are necessary to maintain in balance numerous functions during gestation. Steroidogenesis in the maternal, placental and fetal compartments and the biological effects of progestins and estrogens that play a pivotal role before and during pregnancy are described. Although it is well-known that androgens are considered as substrate for estrogens biosynthesis, their biosynthesis and functionality in placental and other tissues have been questioned. As compared with healthy pregnancy, steroid hormones levels have been found altered in complicated pregnancies and hormonal treatments have been used is some pathologies. Therefore, the aim of this work was to review the biosynthesis, function and regulation of progestins, androgens and estrogens during gestation. Furthermore, steroid hormones concentrations during healthy and complicated pregnancy as well hormonal therapies for the prevention of miscarriages and preterm deliveries are discussed in the present review.

Few-mode fiber true time delay lines for distributed radiofrequency signal processing.

We report, for the first time to our knowledge, distributed radiofrequency signal processing built upon true time delay operation on a step-index few-mode fiber. Two 3-sample configurations with different time delay properties are implemented over the same 60-meter 4-LP-mode fiber link. The inscription of a long period grating at a specific fiber position converts part of the LP01 mode into the LP02, permitting sample time delay engineering. Delay line performance is experimentally demonstrated when applied to radiofrequency signal filtering, example of fiber-distributed processing functionality exhibiting one order or magnitude gain in terms of compactness.

Characterization of a FBG sensor interrogation system based on a mode-locked laser scheme.

This paper is focused on the characterization of a fiber Bragg grating (FBG) sensor interrogation system based on a fiber ring laser with a semiconductor optical amplifier as the gain medium, and an in-loop electro-optical modulator. This system operates as a switchable active (pulsed) mode-locked laser. The operation principle of the system is explained theoretically and validated experimentally. The ability of the system to interrogate an array of different FBGs in wavelength and spatial domain is demonstrated. Simultaneously, the influence of several important parameters on the performance of the interrogation technique has been investigated. Specifically, the effects of the bandwidth and the reflectivity of the FBGs, the SOA gain, and the depth of the intensity modulation have been addressed.

Tilted fiber Bragg gratings in multicore optical fibers for optical sensing.

We have inscribed a tilted fiber Bragg grating (TFBG) in selected cores of a multicore optical fiber. The presence of the TFBG permits to couple light from the incident-guided mode to the cladding modes and to the neighbor cores, and this interaction can be used for optical sensing. We measured different magnitudes: strain, curvature magnitude and direction, and external refractive index. The curvature results show a linear dependence of the maximum crosstalk with the curvature magnitude with a sensitivity of 2.5 dB/m-1 as the curvature magnitude increases and at the same time a wavelength shift of 70 pm/m-1. Changes in the external refractive index gradually vanish the cladding modes resonances and the crosstalk between the different cores, obtaining a reduction of the 90% of the optical spectra integral area for refractive indexes between 1.398 and 1.474.

Multicore fiber-Bragg-grating-based directional curvature sensor interrogated by a broadband source with a sinusoidal spectrum.

A simple, spectral-drift-insensitive interrogation scheme for a multicore fiber Bragg grating (FBG)-based directional curvature sensor is proposed. The basic principle is to transform the wavelength shift of FBGs into the reflected power variation, which is accomplished by utilizing a broadband source with a sinusoidal spectrum. The closed-form expression of the relationship between the reflected power of the FBG and the corresponding peak wavelength is derived for the first time, to the best of our knowledge; therefore, the peak wavelength of the FBG can be precisely interrogated by using a single photodiode. The experimental results show that, with respect to conventional wavelength measurement by an optical spectrum analyzer, the demodulated wavelength error by our proposed interrogation scheme is within ±20 pm. The proposed scheme is further extended to interrogate the direction and curvature using a multicore FBG-based curvature sensor; the interrogated curvature with an error less than 8% is achieved.

Strategies for the quality assessment of the health care service providers in the treatment of Gastric Cancer in Colombia.

BACKGROUND: While, at its inception in 1993, the health care system in Colombia was publicized as a paradigm to be copied across the developing world, numerous problems in its implementation have led to, what is now, an inefficient and crisis-ridden health system. Furthermore, as a result of inappropriate tools to measure the quality of the health service providers, several corruption scandals have arisen in the country. This study attempts to tackle this situation by proposing a strategy for the quality assessment of the health service providers (Entidades Promotoras de Salud, EPS) in the Colombian health system. In particular, as a case study, the quality of the treatment of stomach cancer is analyzed. METHODS: The study uses two complementary techniques to address the problem. These techniques are applied based on data of the treatment of gastric cancer collected on a nation-wide scale by the Colombian Ministry of Health and Welfare. First, Data Envelopment Analysis (DEA) and the Malmquist Index (MI) are used to establish the most efficient EPS's within the system, according to indicators such as opportunity indicators. Second, sequential clustering algorithm, related to process mining a field of data mining, is used to determine the medical history of all patients and to construct typical care pathways of the patients belonging to efficient and inefficient EPS's. Lastly, efforts are made to identify traits and differences between efficient and inefficient EPS's. RESULTS: Efficient and inefficient EPS were identified for the years 2010 and 2011. Additionally, a Malmquist Index was used to calculate the relative changes in the efficiency of the health providers. Using these efficiency rates, the typical treatment path of patients with gastric cancer was found for two EPSs: one efficient and another inefficient. Finally, the typical traits of the care pathways were established. CONCLUSIONS: Combining DEA and process mining proved to be a powerful approach understanding the problem and gaining valuable insight into the inner workings of the Colombian Health System, especially in terms of the treatment process performed by health care providers in critical illnesses such as cancer. However, no sufficiently compelling results were found to establish the contribution of such a combination to evaluate the quality in the delivery of health services.

Time and frequency pump-probe multiplexing to enhance the signal response of Brillouin optical time-domain analyzers.

A technique to enhance the response and performance of Brillouin distributed fiber sensors is proposed and experimentally validated. The method consists in creating a multi-frequency pump pulse interacting with a matching multi-frequency continuous-wave probe. To avoid nonlinear cross-interaction between spectral lines, the method requires that the distinct pump pulse components and temporal traces reaching the photo-detector are subject to wavelength-selective delaying. This way the total pump and probe powers launched into the fiber can be incrementally boosted beyond the thresholds imposed by nonlinear effects. As a consequence of the multiplied pump-probe Brillouin interactions occurring along the fiber, the sensor response can be enhanced in exact proportion to the number of spectral components. The method is experimentally validated in a 50 km-long distributed optical fiber sensor augmented to 3 pump-probe spectral pairs, demonstrating a signal-to-noise ratio enhancement of 4.8 dB.

In vivo dual targeting of the oncogenic Ether-à-go-go-1 potassium channel by calcitriol and astemizole results in enhanced antineoplastic effects in breast tumors.

BACKGROUND: The oncogenic ether-à-go-go-1 potassium channel (EAG1) activity and expression are necessary for cell cycle progression and tumorigenesis. The active vitamin D metabolite, calcitriol, and astemizole, a promising antineoplastic drug, target EAG1 by inhibiting its expression and blocking ion currents, respectively. We have previously shown a synergistic antiproliferative effect of calcitriol and astemizole in breast cancer cells in vitro, but the effect of this dual therapy in vivo has not been studied. METHODS: In the present study, we explored the combined antineoplastic effect of both drugs in vivo using mice xenografted with the human breast cancer cell line T-47D and a primary breast cancer-derived cell culture (MBCDF). Tumor-bearing athymic female mice were treated with oral astemizole (50 mg/kg/day) and/or intraperitoneal injections of calcitriol (0.03 µg/g body weight twice a week) during 3 weeks. Tumor sizes were measured thrice weekly. For mechanistic insights, we studied EAG1 expression by qPCR and Western blot. The expression of Ki-67 and the relative tumor volume were used as indicators of therapeutic efficacy. RESULTS: Compared to untreated controls, astemizole and calcitriol significantly reduced, while the coadministration of both drugs further suppressed, tumor growth (P < 0.05). In addition, the combined therapy significantly downregulated tumoral EAG1 and Ki-67 expression. CONCLUSIONS: The concomitant administration of calcitriol and astemizole inhibited tumor growth more efficiently than each drug alone, which may be explained by the blocking of EAG1. These results provide the bases for further studies aimed at testing EAG1-dual targeting in breast cancer tumors expressing both EAG1 and the vitamin D receptor.

Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: a potential new therapeutic approach.

BACKGROUND: Approximately 30% of breast tumors do not express the estrogen receptor (ER) α, which is necessary for endocrine therapy approaches. Studies are ongoing in order to restore ERα expression in ERα-negative breast cancer. The aim of the present study was to determine if calcitriol induces ERα expression in ER-negative breast cancer cells, thus restoring antiestrogen responses. METHODS: Cultured cells derived from ERα-negative breast tumors and an ERα-negative breast cancer cell line (SUM-229PE) were treated with calcitriol and ERα expression was assessed by real time PCR and western blots. The ERα functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were assessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-à-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical analyses were determined by one-way ANOVA. RESULTS: Calcitriol was able to induce the expression of a functional ERα in ER-negative breast cancer cells. This effect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly, the calcitriol-induced ERα restored the response to antiestrogens by inhibiting cell proliferation. In addition, calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell proliferation regulators CCND1 and EAG1. CONCLUSIONS: Calcitriol induced the expression of ERα and restored the response to antiestrogens in ERα-negative breast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic strategy in ERα-negative breast cancer patients.

In Vitro Human Endometrial Cells and In Vivo Rat Model Studies Suggest That Ulipristal Acetate Impacts Endometrial Compatibility for Embryo Implantation.

BACKGROUND: Ulipristal acetate (UPA) and levonorgestrel are used as emergency hormonal contraceptives. Although both are highly effective in preventing pregnancy, UPA shows efficacy even when taken up to 120 h after unprotected sexual intercourse. AIMS: To investigate whether the mechanism of UPA's contraceptive action involves post-fertilization effects. METHODS: In vitro and in vivo studies using cultured human endometrial cells and a pre-clinical rat model. RESULTS: Endometrial cells treated with UPA showed changes in the expression of receptivity gene markers and a significant decrease in trophoblast spheroids attached to the cultured cells. In addition, administration of UPA to female unmated rats decreased the expression of implantation-related genes in the endometrium and inhibited the number of implantation sites in the mated group compared to the non-treated group. CONCLUSIONS: These results support that UPA as an emergency contraceptive might have post-fertilization effects that may affect embryo implantation.

Transcriptional landscape of human trophoblast cells treated with calcitriol and TGF-ß1.

Calcitriol and transforming growth factor beta 1 (TGF-ß1) are unrelated molecules that regulate biological processes according to the genetic target, cell type, and context. Several studies have shown independent effects of calcitriol and TGF-ßs on the placenta, but there is no information regarding the impact of their combination on these cells. Therefore, this study analyzed the effects of calcitriol, TGF-ß1, and their combination in primary cultures of human trophoblast cells using a whole genome expression microarray. Data analysis revealed a set of differentially expressed genes induced by each treatment. Enrichment pathway analysis identified modulatory effects of calcitriol on genes related to metabolic processes such as vitamin D, steroid, and fat-soluble vitamins as well as antimicrobial and immune responses. In relation to TGF-ß1, the analysis showed a few differentially expressed genes that were mainly associated with the neutrophil immune response. Lastly, the analysis revealed that the combination of calcitriol and TGF-ß1 up-regulated genes involving both immunologic processes and the biosynthesis of unsaturated fatty acids, eicosanoids, and lipoxins, among others. In contrast, pathways down-regulated by the combination were mostly associated with the catabolic process of acylglycerols and peptides, PPAR signaling pathway, cellular response to low-density lipoprotein stimulus, renin angiotensin system and digestion, mobilization and transport of lipids. Consistent with these results, the combined treatment on human trophoblast cells induced the accumulation of intracellular neutral lipid droplets and stimulated both gene and protein expression of 15-hydroxyprostaglandin dehydrogenase. In conclusion, the results revealed that differentially expressed genes induced by the combination modified the transcriptional landscape compared to each treatment alone, mainly altering the storage, activity and metabolism of lipids, which might have an impact on placental development.

Effects of calcitriol upon TGF-ßs and their receptors in trophoblast cells.

Calcitriol levels increase during pregnancy, contributing to the hormonal and immunological balance, but its deficiency has been associated with problems during this period. Meanwhile, transforming growth factors-ß (TGF-ßs) play an important role in the maintenance of fetal-maternal immune tolerance; however, exacerbated concentrations of this growth factor are associated with complicated pregnancies. Therefore, we studied the effects of calcitriol on TGF-ßs and their receptors in trophoblast cells. Term placentas from uncomplicated pregnancies after cesarean sections were used for cell cultures. Basal gene expression and the effect of calcitriol upon TGF-ß1, TGF-ß2, TGF-ß3, and their receptors TGF-ßR1 and TGF-ßR2 were assessed using real-time PCR from trophoblast cells. The presence of TGF-ß1, 2, 3, and TGF-ßR1 were evaluated by immunofluorescence, and the protein abundance and secretion of TGF-ß1 were assessed by Western blot and ELISA, respectively. Basal gene expression of TGF-ß1 in trophoblast from term placentas was higher than TGF-ß2 and TGF-ß3, while TGF-ßR2 was higher than TGF-ßR1. The presence and cellular localization of TGF-ß1, 2, 3, and TGF-ßR1 were detected in the cytoplasm of syncytiotrophoblast, with TGF-ß1 showing the highest intensity. Calcitriol significantly inhibited gene expression of TGF-ß1, TGF-ß2, and TGF-ßR1. Likewise, calcitriol decreased the secretion and abundance of TGF-ß1. In conclusion, results indicate that calcitriol is a regulator of TGF-ßs in cultured trophoblast cells from term placentas and therefore may be an important player in the development of healthy pregnancies.

Associations between insulin-like growth factor I, vascular endothelial growth factor and its soluble receptor 1 in umbilical serum and endothelial cells obtained from normotensive and preeclamptic pregnancies.

The aim of this study was to investigate the associations between insulin-like growth factor I (IGF-I) with vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in umbilical serum and to study the effects of IGF-I upon sFlt-1 synthesis in human umbilical vein endothelial cells (HUVEC) in normotensive (NT) and preeclamptic (PE) pregnancies. As compared with the NT group, umbilical serum IGF-I and VEGF levels were lower in the PE group, while sFlt-1 concentrations were higher. Levels of sFlt-1 correlated with IGF-I in the NT group and with VEGF in the PE group. Basal concentration of sFlt-1 in HUVEC culture media was higher in the PE group. IGF-I stimulated sFlt-1 synthesis only in the NT group. In summary, umbilical serum sFlt-1 is associated with IGF-I in normotensive pregnancy and with VEGF in preeclampsia. IGF-I stimulates sFlt-1 synthesis in endothelial cells in normotensive but not in PE pregnancies.

Time-frequency analysis of long fiber Bragg gratings with low reflectivity.

A new technique to investigate the spatial distribution of the reflection spectrum along fabricated long weak fiber Bragg gratings (FBG) is experimentally demonstrated, together with its potential applications for distributed fiber sensing and broadband signal processing. A short pulsed coherent light signal is launched into a FBG and the signal frequency is scanned through the FBG reflection spectrum. When the pulse duration is set much shorter than the transit time through the grating a time-resolved reflected signal can be obtained for each signal frequency. It informs about the distribution of the refractive index periodic perturbation along the entire FBG length, hence the uniformity or frequency chirp information of the fabricated FBG. This technique has been implemented to demonstrate a distributed temperature sensing system with high spatial resolution and to also realize a robust all-fiber tunable delay line for broadband signals.