Simultaneous bilateral dual mobility total hip arthroplasty dislocation in a patient with hepatic encephalopathy: A case report

Luxació; Mobilitat dual; Encefalopatia hepàticaDislocación; Movilidad dual; Encefalopatía hepáticaDislocation; Dual mobility; Hepatic encephalopathyIntroduction and importance Dislocation is a severe complication after total hip arthroplasty (THA). It is one of the most common reasons for failure and revision surgery. This is the first case of a documented simultaneous bilateral dual mobility (DM) THA dislocation. Case presentation A forty-nine-year-old man presented with bilateral hip pain, immobility and deformity. X-ray images demonstrated simultaneous bilateral posterior THA dislocation. Previously, the patient had presented atraumatic dislocations recurrently. When he was thoroughly re-interrogated, he complained of uncontrolled and generalized muscle contractions, which were compatible with myoclonus due to hepatic encephalopathy (HE). Multidisciplinary treatment was performed satisfactorily to control myoclonus symptomatology and to prevent dislocation. Clinical discussion Patient’s most important risk factor was a neuromuscular disorder, which we initially gave little notice and undervalued. HE is a serious but reversible syndrome, observed in patients with liver dysfunction. It leads to a wide spectrum of neuropsychiatric abnormalities. Management is based on prevention of episodes, avoiding the underlying triggers. Due to the high risk for dislocation of our patient, we decided to use DM cups bilaterally. This system has demonstrated lower rates of dislocation. Conclusion This case report reminds us that a careful evaluation through meticulous history and physical examination are mandatory when faced with recurrent instability. Furthermore, prevention of dislocation is vastly preferable to treating this challenging complication. High-risk patients should be identified, and appropriate surgical approach, technique and implants have to be collectively used to reach a strategy that mitigates and ideally prevents dislocation

Phase I/II study of the LAG-3 inhibitor ieramilimab (LAG525) ± anti-PD-1 spartalizumab (PDR001) in patients with advanced malignancies

Combination; Drug therapy; ImmunotherapyCombinació; Teràpia farmacològica; ImmunoteràpiaCombinación; Terapia farmacológica; InmunoterapiaBackground Lymphocyte-activation gene 3 (LAG-3) is an inhibitory immunoreceptor that negatively regulates T-cell activation. This paper presents preclinical characterization of the LAG-3 inhibitor, ieramilimab (LAG525), and phase I data for the treatment of patients with advanced/metastatic solid tumors with ieramilimab ±the anti-programmed cell death-1 antibody, spartalizumab. Methods Eligible patients had advanced/metastatic solid tumors and progressed after, or were unsuitable for, standard-of-care therapy, including checkpoint inhibitors in some cases. Patients received ieramilimab ±spartalizumab across various dose-escalation schedules. The primary objective was to assess the maximum tolerated dose (MTD) or recommended phase II dose (RP2D). Results In total, 255 patients were allocated to single-agent ieramilimab (n=134) and combination (n=121) treatment arms. The majority (98%) had received prior antineoplastic therapy (median, 3). Four patients experienced dose-limiting toxicities in each treatment arm across various dosing cohorts. No MTD was reached. The RP2D on a 3-week schedule was declared as 400 mg ieramilimab plus 300 mg spartalizumab and, on a 4-week schedule (once every 4 weeks; Q4W), as 800 mg ieramilimab plus 400 mg spartalizumab; tumor target (LAG-3) suppression with 600 mg ieramilimab Q4W was predicted to be similar to the Q4W, RP2D schedule. Treatment-related adverse events (TRAEs) occurred in 75 (56%) and 84 (69%) patients in the single-agent and combination arms, respectively. Most common TRAEs were fatigue, gastrointestinal, and skin disorders, and were of mild severity; seven patients experienced at least one treatment-related serious adverse event in the single-agent (5%) and combination group (5.8%). Antitumor activity was observed in the combination arm, with 3 (2%) complete responses and 10 (8%) partial responses in a mixed population of tumor types. In the combination arm, eight patients (6.6%) experienced stable disease for 6 months or longer versus six patients (4.5%) in the single-agent arm. Responding patients trended towards having higher levels of immune gene expression, including CD8 and LAG3, in tumor tissue at baseline. Conclusions Ieramilimab was well tolerated as monotherapy and in combination with spartalizumab. The toxicity profile of ieramilimab in combination with spartalizumab was comparable to that of spartalizumab alone. Modest antitumor activity was seen with combination treatment.This study was sponsored by Novartis Pharmaceuticals Corporation and preliminary results were previously presented at ASCO 2018

Time Expansion in Distributed Optical Fiber Sensing

Distributed optical fiber sensing (DOFS) technology has recently experienced an impressive growth in various fields including security, structural monitoring and seismology, among others. This expansion has been accompanied by a speedy development of the technology in the last couple of decades, reaching remarkable performance in terms of sensitivity, range, number of independent sensing points and affordable cost per monitored point as compared with competing technologies such as electrical or point optical sensors. Phase-sensitive Optical Time-Domain Reflectometry (φOTDR) is a particularly interesting DOFS technique, since it enables real-time monitoring of dynamic variations of physical parameters over a large number of sensing points. Compared to their frequency-domain counterparts (OFDR), φOTDR sensors typically provide higher dynamics and longer ranges but significantly worse spatial resolutions. Very recently, a novel φOTDR approach has been introduced, which covers an existing gap between the long range and fast response of φOTDR and the high spatial resolution of OFDR. This technique, termed time-expanded (TE) φOTDR, exploits an interferometric scheme that employs two mutually coherent optical frequency combs. In TE-φOTDR, a probe comb is launched into the fiber under test. The beating of the backscattered light and a suitable LO comb produces a multi-heterodyne detection process that compresses the spectrum of the probe comb, in turn expanding the detected optical traces in the time-domain. This approach has allowed sensing using φOTDR technology with very high resolution (in the cm scale), while requiring outstandingly low detection and acquisition bandwidths (sub-MHz). In this work, we review the fundamentals of TE-φOTDR technology and describe the recent developments, focusing on the attainable sensing performance, the existing trade-offs and open working lines of this novel sensing approach.The work of María R. Fernández-Ruiz and Hugo F. Martins was supported in part by the MCIN/AEI/10.13039/501100011033 and in part by European Union NextGenerationEU»/PRTR under Grants RYC2021-032167-I and RYC2021-035009-I. The work of Miguel SorianoAmat and Vicente Durán was supported in part by MCIN/AEI/10.13039/ 501100011033 and in part by the FSE invierte en tu futuro under Grants PRE-2019-087444 and RYC-2017-23668. This work was supported in part by Comunidad de Madrid and Feder Program under Grant SINFOTON2-CM: S2018/NMT-4326, in part by Generalitat Valenciana under Grant PROMETEO/2020/029, in part by the Universitat Jaume I under Grant UJIB2022-53, in part by the Spanish MCIN/AEI/10.13039/501100011033 and European Union NextGenerationEU/PRTR Program under Grants PSI ref. PLEC2021-007875 and TREMORS ref. CPP2021-008869, in part by the Spanish MCIN/AEI/10.13039/501100011033 and FEDER Una manera de hacer Europa under Grants PID2021-128000OB-C21, PID2021-128000OB-C22, and PID2021-124814NB-C22, and in part by the European Innovation Council under Grant SAFE: ref. 10109899

Time expansion in distributed optical fiber sensing

The work of MRFR and HFM was supported by the MCIN/AEI/10.13039/501100011033 and European Union NextGenerationEU»/PRTR under grants RYC2021-032167-I and RYC2021- 035009-I. The work of MSA and VD was supported by MCIN/AEI/10.13039/ 501100011033 and the FSE invierte en tu futuro under grants PRE-2019- 087444 and RYC-2017-23668, respectively.Distributed optical fiber sensing (DOFS) technology has recently experienced an impressive growth in various fields including security, structural monitoring and seismology, among others. This expansion has been accompanied by a speedy development of the technology in the last couple of decades, reaching remarkable performance in terms of sensitivity, range, number of independent sensing points and affordable cost per monitored point as compared with competing technologies such as electrical or point optical sensors. Phase-sensitive Optical Time-Domain Reflectometry (ϕOTDR) is a particularly interesting DOFS technique, since it enables real-time monitoring of dynamic variations of physical parameters over a large number of sensing points. Compared to their frequency-domain counterparts (OFDR), ϕOTDR sensors typically provide higher dynamics and longer ranges but significantly worse spatial resolutions. Very recently, a novel ϕOTDR approach has been introduced, which covers an existing gap between the long range and fast response of ϕOTDR and the high spatial resolution of OFDR. This technique, termed time-expanded (TE) ϕOTDR, exploits an interferometric scheme that employs two mutually coherent optical frequency combs. In TE-ϕOTDR, a probe comb is launched into the fiber under test. The beating of the backscattered light and a suitable LO comb produces a multi-heterodyne detection process that compresses the spectrum of the probe comb, in turn expanding the detected optical traces in the time-domain. This approach has allowed sensing using ϕOTDR technology with very high resolution (in the cm scale), while requiring outstandingly low detection and acquisition bandwidths (sub-MHz). In this work, we review the fundamentals of TE-ϕOTDR technology and describe the recent developments, focusing on the attainable sensing performance, the existing trade-offs and open working lines of this novel sensing approach.Comunidad de MadridMinisterio de Ciencia e InnovaciónAgencia Estatal de InvestigaciónGeneralitat ValencianaUniversitat Jaume IEuropean Commissio

Time-expanded phase-sensitive optical time-domain reflectometry

Phase-sensitive optical time-domain reflectometry (ΦOTDR) is a well-established technique that provides spatio-temporal measurements of an environmental variable in real time. This unique capability is being leveraged in an ever-increasing number of applications, from energy transportation or civil security to seismology. To date, a wide number of different approaches have been implemented, providing a plethora of options in terms of performance (resolution, acquisition bandwidth, sensitivity or range). However, to achieve high spatial resolutions, detection bandwidths in the GHz range are typically required, substantially increasing the system cost and complexity. Here, we present a novel ΦOTDR approach that allows a customized time expansion of the received optical traces. Hence, the presented technique reaches cm-scale spatial resolutions over 1 km while requiring a remarkably low detection bandwidth in the MHz regime. This approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered light. Random phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme. A comparison of the proposed method with alternative approaches aimed at similar operation features is provided, along with a thorough analysis of the new trade-offs. Our results demonstrate a radically novel high-resolution ΦOTDR scheme, which could promote new applications in metrology, borehole monitoring or aerospace

Time-expanded FOTDR based on Orthogonal Polarization Frequency Comb generation

Phase-sensitive Optical Time-Domain Reflectometry (ΦOTDR) has emerged as an effective and high-performance solution within the realm of Distributed Optical Fiber Sensing (DOFS) technologies, which has promoted its use in an ever-growing number of fields. The challenges arisen by new operation fields demand surpassing the historical trade-offs in this technology, specially aiming for higher resolution without jeopardizing the system simplicity and cost-effectiveness. In this context, time-expanded (TE-)ΦOTDR has been recently proposed as a DOFS solution delivering cm-range resolution with sub-MHz detection and acquisition bandwidths. It is based on the use of an interferometric scheme that employs a dual frequency comb (DFC), consisting of two mutually coherent optical frequency combs with dissimilar repetition rates. In this paper, we present a novel DFC generation scheme for TE-ΦOTDR that exploits the polarization orthogonality. In particular, our approach considerably increases the common path followed by the two frequency combs, thus reducing instability and noise as compared to the conventional generation scheme. Additionally, we employ an IQ modulation scheme with two PRBS generators that increases the scalability of the interrogator while severely reducing its cost and complexity. Results show a reduction in the noise amplitude spectral density especially at low frequency values, which corroborates the stability enhancement of this proposed architecture as compared to the conventional scheme

Common-Path Dual-Comb Spectroscopy Using a Single Electro-Optic Modulator

Dual frequency comb (DFC) spectroscopy using electro-optic comb generators stands out for its flexibility, easy implementation, and low cost. Typically, two combs with different line spacing are generated from a common laser using independent electro-optic comb generators. This approach minimizes the impact of laser phase noise; however, the distinct paths followed by the two combs ultimately limit the attainable signal-to-noise ratio and long-term stability of the system. In this work, a common-path DFC is generated using a single modulator driven by an arbitrary waveform generator, thus enabling a remarkable increase of the system stability (up to 0.8 s of integration time) while maintaining high flexibility. The proposed technique is experimentally validated by implementing a dual frequency comb with 3000 lines, covering an optical bandwidth of 4.5 GHz, and demonstrating an optical-to-radiofrequency compression factor of 7500. Our system is able to measure extremely narrowband optical features (in the MHz range) with an accuracy only limited by the master laser stability

Influencia contextual sobre las creencias y actitudes hacia la menstruación en estudiantes de cuarto y quinto de secundaria de instituciones educativas publicas y privadas de Arequipa

La menstruación es un evento natural que forma parte de la identidad femenina. Por tanto, como todo evento natural los seres humanos formamos creencias y actitudes asociadas a dicho evento. Las actitudes no son universales y se construyen dependiendo del contexto en el cual la persona fue formada y socializada. Las actitudes hacia la menstruación se construyen durante la adolescencia puesto que es durante esta etapa que el evento comienza a ser importante para su vida. Sin embargo, las actitudes en esta etapa también dependen de la socialización de pares, por lo que el pertenecer a instituciones educativas de mujeres, de hombres o mixtas afectaría al resultado de la percepción de la menstruación. Una perspectiva que permite dar sentido a las diferencias actitudinales según el contexto, es el modelo ecológico de Bronfenbrenner (1986). Este punto resulta relevante puesto que percepciones negativas acerca de la menstruación podrían afectar al desenvolvimiento pleno y natural de la mujer en la sociedad actual. Por tanto, el objetivo del presente estudio es determinar las creencias y actitudes en relación con la menstruación que tienen los adolescentes pertenecientes a instituciones educativas privadas y públicas, de tipo diferenciado y mixto en la ciudad de Arequipa. La muestra estuvo conformada por 894 (52% hombres) alumnos de 4to y 5to de secundaria de seis instituciones educativas de la ciudad de Arequipa. Los instrumentos utilizados fueron el Cuestionario de Creencias y Actitudes acerca de la Menstruación (Ramírez ,2003) y una ficha sociodemográfica. Los resultados indican que tanto hombres como mujeres consideran a la menstruación como un evento molesto. Así mismo se encontró que las instituciones educativas públicas y una institución privada masculina, muestran una visión más estereotipada de la menstruación, en comparación a las otras instituciones educativas.Tesi

The nature of the silicaphilic fluorescence of PDMPO

PDMPO (2-(4-pyridyl)-5-((4-(2-dimethylaminoethylaminocarbamoyl)methoxy)phenyl)oxazole), has unique silica specific fluorescence and is used in biology to understand biosilicification. This ‘silicaphilic’ fluorescence is not well understood nor is the response to local environmental variables like solvent and pH. We investigated PDMPO in a range of environments: using UV-vis and fluorescence spectroscopy supported by computational data, (SPARC, molecular dynamics simulations, density functional theory calculations), dynamic light scattering and zeta potential measurements to understand the PDMPO–silica interaction. From absorption data, PDMPO exhibited a pKa of 4.20 for PDMPOH22+ to PDMPOH+ . Fluorescence emission measurements revealed large shifts in excited state pKa* values with different behaviour when bound to silica (pKa* of 10.4). PDMPO bound to silica particles is located in the Stern layer with the dye exhibiting pH dependent depolarising motion. In aqueous solution, PDMPO showed strong chromaticity with correlation between the maximum emission wavelength for PDMPOH+* and dielectric constant (4.8–80). Additional chromatic effects were attributed to changes in solvent accessible surface area. Chromatic effects were also observed for silica bound dye which allow its use as a direct probe of bulk pH over a range far in excess of what is possible for the dye alone (3–5.2). The unique combination of chromaticity and excited state dynamics allows PDMPO to monitor pH from 3 to 13 while also reporting on surface environment opening a new frontier in the quantitative understanding of (bio)silicification

Monitoring of a highly flexible aircraft model wing using time-expanded phase-sensitive OTDR

In recent years, the use of highly flexible wings in aerial vehicles (e.g., aircraft or drones) has been attracting increasing interest, as they are lightweight, which can improve fuel-efficiency and distinct flight performances. Continuous wing monitoring can provide valuable information to prevent fatal failures and optimize aircraft control. In this paper, we demonstrate the capabilities of a distributed optical fiber sensor based on time-expanded phase-sensitive optical time-domain reflectometry (TE-ΦOTDR) technology for structural health monitoring of highly flexible wings, including static (i.e., bend and torsion), and dynamic (e.g., vibration) structural deformation. This distributed sensing technology provides a remarkable spatial resolution of 2 cm, with detection and processing bandwidths well under the MHz, arising as a novel, highly efficient monitoring methodology for this kind of structure. Conventional optical fibers were embedded in two highly flexible specimens that represented an aircraft wing, and different bending and twisting movements were detected and quantified with high sensitivity and minimal intrusiveness