ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.

BACKGROUND: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts. METHODS: We developed ClinPrior, a novel method for the analysis of WES/WGS data that ranks candidate causal variants based on the patient's standardized phenotypic features (in Human Phenotype Ontology (HPO) terms). The algorithm propagates the data through an interactome network-based prioritization approach. This algorithm was thoroughly benchmarked using a synthetic patient cohort and was subsequently tested on a heterogeneous prospective, real-world series of 135 families affected by hereditary spastic paraplegia (HSP) and/or cerebellar ataxia (CA). RESULTS: ClinPrior successfully identified causative variants achieving a final positive diagnostic yield of 70% in our real-world cohort. This includes 10 novel candidate genes not previously associated with disease, 7 of which were functionally validated within this project. We used the knowledge generated by ClinPrior to create a specific interactome for HSP/CA disorders thus enabling future diagnoses as well as the discovery of novel disease genes. CONCLUSIONS: ClinPrior is an algorithm that uses standardized phenotype information and interactome data to improve clinical genomic diagnosis. It helps in identifying atypical cases and efficiently predicts novel disease-causing genes. This leads to increasing diagnostic yield, shortening of the diagnostic Odysseys and advancing our understanding of human illnesses.

Experiencia SEFAC Semana Sin Humo 2021 / Experience SEFAC Smoke-free Week 2021

JUSTIFICACIÓN: para el Día Mundial Sin Tabaco, Fundación SEFAC y SEFAC, realizaron su campaña “Semana Sin Humo 2021”, en redes sociales dirigida tanto a Farmacéuticos Comunitarios como a pacientes, para concienciar a ambos de que el farmacéutico comunitario puede ayudar de manera eficaz a dejar de fumar. Objetivos: -Potenciar y dar herramientas que empoderen a los farmacéuticos comunitarios para realizar el consejo breve a través de videos cortos formativos e informativos.-Informar, promover y dar a conocer entre los pacientes la oportunidad del cese tabáquico que de manera accesible y profesional pueden hacer en la farmacia comunitaria.MATERIAL Y MÉTODOS: se editaron 6 videos cortos realizados por FC del grupo de Respiratorio y Tabaquismo de SEFAC, difundidos en las redes sociales (Twitter e Instagram) durante la “Semana Sin Humo 2021”, 4 dirigidos a farmacéuticos comunitarios y 2 a pacientes.RESULTADOS: durante la duración de la campaña, los videos tuvieron un total de 3167 visualizaciones, con una media de 527,8 por video. Los dirigidos a los farmacéuticos comunitarios tuvieron una media de 488 visualizaciones, frente a 607,5 los de los pacientes. Contenido del vídeo. Visualizaciones. Las 5As del consejo breve para ayudar a dejar de fumar en farmacia comunitaria 880 'Semana sin humo': cinco razones para dejar de fumar 665 Intervención según el tipo de paciente fumador 425¿Qué tratamientos pueden encontrarse en la farmacia comunitaria? 550Caso práctico: intervención breve en cesación tabáquica 291 Guía de actuación farmacéutica a pie de mostrador: la terapia sustitutiva con nicotina 356 TOTAL3.167 (AU)

Upconversion thermometry: a new tool to measure the thermal resistance of nanoparticles.

The rapid evolution in luminescence thermometry in the last few years gradually shifted the research from the fabrication of more sensitive nanoarchitectures towards the use of the technique as a tool for thermal bioimaging and for the unveiling of properties of the thermometers themselves and of their local surroundings, for example to evaluate heat transport at unprecedented small scales. In this work, we demonstrated that KLu(WO4)2:Ho3+,Tm3+ nanoparticles are able to combine controllable heat release and upconversion thermometry permitting to estimate its thermal resistance (in air), a key parameter to model the heat transfer at the nanoscale.

Anisotropic enhancement of Yb3+ luminescence by disordered plasmonic networks self-assembled on RbTiOPO4 ferroelectric crystals.

Increasing Yb3+ absorption efficiency is currently desired in a number of applications including bio-imaging, photovoltaics, near infrared driven photocatalysis or ultra-short pulsed solid-state lasers. In this work, silver nanoparticles, which are connected forming disordered networks, have been self-assembled on Yb3+ doped RbTiOPO4 crystals to produce a remarkable enhancement of Yb3+ absorption, and hence in the photoluminescence of this ion. The results are interpreted taking into account the near-field response of the plasmonic networks, which display strong amplification of the electric field at the maximum of Yb3+ excitation at around 900 nm, together with the anisotropic character of the Yb3+ transitions in RbTiOPO4. We show that in the near field regime, the scattering of the plasmonic networks produces additional polarization field components to those of the incident field, which allows access to the largest transition dipolar moment of Yb3+ ions in RbTiOPO4. As a result, a much more efficient route for Yb3+ excitation takes place at the immediacy of the plasmonic networks. This work provides fundamental insights for improving the optical properties of rare earth ions by the suitable design of metallic nanoparticle arrangements, and constitutes a promising step towards the development of new multifunctional solid-state lasers.

Sub-Femto-g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results.

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1 fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15} g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3) fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5 mHz we observe a low-frequency tail that stays below 12 fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

Sub-nanosecond Yb:KLu(WO4)2 microchip laser.

A diode-pumped Yb:KLu(WO4)2 microchip laser passively Q-switched by a Cr4+:YAG saturable absorber generated a maximum average output power of 590 mW at 1031 nm with a slope efficiency of 55%. The pulse characteristics were 690 ps/47.6 µJ at a pulse repetition frequency of 12.4 kHz. The output beam had an excellent circular profile with M2<1.05. Yb:KLu(WO4)2 is very promising for ultrathin sub-ns microchip lasers.

Passive Q-switching of a Tm,Ho:KLu(WO4)2 microchip laser by a Cr:ZnS saturable absorber.

A diode-pumped Tm,Ho:KLu(WO4)2 microchip laser passively Q-switched with a Cr:ZnS saturable absorber generated an average output power of 131 mW at 2063.6 nm with a slope efficiency of 11% and a Q-switching conversion efficiency of 58%. The pulse characteristics were 14 ns/9 µJ at a pulse repetition frequency of 14.5 kHz. With higher modulation depth of the saturable absorber, 9 ns/10.4 µJ/8.2 kHz pulses were generated at 2061.1 nm, corresponding to a record peak power extracted from a passively Q-switched Tm,Ho laser of 1.15 kW. A theoretical model is presented, predicting the pulse energy and duration. The simulations are in good agreement with the experimental results.

Benefits of Silica Core-Shell Structures on the Temperature Sensing Properties of Er,Yb:GdVO4 Up-Conversion Nanoparticles.

We studied the temperature-dependent luminescence of GdVO4 nanoparticles co-doped with Er(3+) (1 mol %) and Yb(3+) (20 mol %) and determined their thermal sensing properties through the fluorescence intensity ratio (FIR) technique. We also analyzed how a silica coating, in a core-shell structure, affects the temperature sensing properties of this material. Spectra were recorded in the range of biological temperatures (298-343 K). The absolute sensitivity for temperature determination calculated for the core-shell nanoparticles is double the one calculated for bare nanoparticles, achieving a thermal resolution of 0.4 K. Moreover, silica-coated nanoparticles show good dispersibility in different solvents, such as water, DMSO, and methanol. Also, they show good luminescence stability without interactions with solvent molecules. Furthermore, we also observed that the silica coating shell prevents progressive heating of the nanoparticles during prolonged excitation periods with the 980 nm laser, preventing effects on their thermometric applications.

Nefrectomía laparoscópica de donante vivo: experiencia de 75 casos consecutivos / Live donor laparoscopic nephrectomy: experience in 75 cases

Background: Live Donor Laparoscopic Nephrectomy (LDLN) has substantial benefits when compared with open nephrectomy such as shorter hospital stay, prompt return to work, less post-operative pain, better cosmetic results, less blood loss and less surgical wound infections. It is the mode of choice for safely harvesting a kidney for organ transplantation. Aim: To describe the surgical results of LDLN in a pioneer renal transplant center in Chile. Material and Methods: Review of clinical records of 75 subjects aged 27 to 60 years (37 males) subjected to a LDLN in a public hospital between 1998 and 2013. Information about clinical and surgical data and perioperative complications was retrieved. Results: No subject died. All kidneys were satisfactorily implanted in their receptors. The mean operative time was 116 minutes. Mean hospital stay was 1.6 days, warm ischemia time was 6.8 minutes, and cold ischemia time was 31.5 minutes. Operative adverse events occurred in 8 percent. The conversion and reoperation rates were 4 and 1.3 percent, respectively. Among receptors, 1.5 percent evolved with Acute Tubular Necrosis and 2.2 percent required graft excision. Conclusions: LDLN is a safe and pioneering surgical technique in Chile. Its results are satisfactory and comparable to those obtained with classic lumbotomy.

Introducción: El trasplante renal es en la actualidad el tratamiento de elección de la Insuficiencia Renal Crónica Terminal. La Nefrectomía Laparoscópica del Donante Vivo (NLDV) tiene ventajas sustanciales en relación a la Nefrectomía Clásica. Entre estas se destacan una menor estancia hospitalaria, pronto regreso a la actividad laboral, disminución del dolor post-operatorio, mejores resultados cosméticos, menor pérdida de volumen sanguíneo y una disminución de infecciones de heridas operatorias, consolidándose como la primera prioridad como forma de obtener un órgano para trasplante renal. El presente trabajo tiene como objetivo mostrar la casuística y complicaciones en el Hospital Barros Luco-Trudeau (HBLT), como centro pionero en NLDV en nuestro país. Material y Método: Estudio retrospectivo de corte transversal. Se realiza una revisión de registros clínicos de 75 NLDV realizadas entre 1998-2013, seleccionando datos demográficos, clínicos y quirúrgicos de donantes y receptores, con un especial énfasis en relación a complicaciones peri-operatorias. Resultados: Sin mortalidad. Todos los riñones fueron implantados satisfactoriamente en sus respectivos receptores. Cirugía con duración promedio de 116 min, estadía hospitalaria promedio de 1,6 días, isquemia caliente promedio de 6,8 min e isquemia fría promedio de 31,5 min. Incidentes operatorios 8 por ciento y 4 por ciento conducentes a conversión. Tasa de reoperación de 1,3 por ciento. En cuanto a receptores, un 1,5 por ciento desarrolla Necrosis Tubular Aguda. 2,2 por ciento requiere transplantectomía. Discusión: La NLDV representa una técnica segura, que ha llegado a constituir el 100 por ciento de las nefrectomías de donantes vivos realizadas durante los últimos tres años. Los resultados son satisfactorios y plenamente comparables a los resultados obtenidos por lumbotomía clásica y de otros centros de alto volumen laparoscópico a nivel internacional.

Er:Yb:NaY2F5O up-converting nanoparticles for sub-tissue fluorescence lifetime thermal sensing.

Non-contact thermometry is essential in biomedical studies requiring thermal sensing and imaging with high thermal and spatial resolutions. In this work, we report the potential use of Er:Yb:NaYF4 and Er:Yb:NaY2F5O up-conversion nanoparticles as thermal sensors by means of lifetime based luminescent thermometry. We demonstrate how Er:Yb:NaY2F5O nanocrystals present a higher thermal sensitivity than the Er:Yb:NaYF4 ones and that their lifetime thermal coefficient is comparable to those corresponding to other nano-sized luminescent systems already used for high resolution lifetime fluorescence thermal sensing. We evaluate the potential use of Er:Yb:NaY2F5O nanoparticles as lifetime based thermal probes by providing the first experimental evidence on sub-tissue lifetime fluorescence thermal sensing by using up-conversion nanoparticles in an ex vivo experiment.

White light upconversion in Yb-sensitized (Tm, Ho)-doped KLu(WO4)2 nanocrystals: the effect of Eu incorporation.

Monoclinic Yb-sensitized (Tm, Ho)-doped KLu(WO4)2 nanocrystals of ~100 nm size have been synthesized by the modified Pechini sol-gel method. Their diode laser near-infrared (~980 nm) excited upconversion emission properties have been characterized at power densities in the range 30-355 W cm(-2). Bright white light composed of blue ~475 nm, green ~540 nm, and red ~650 nm emissions, corresponding to Tm(3+ 1)G4 → (3)H6, Ho(3+ 5)S2, (5)F4 → (5)I8, and Ho(3+ 5)F5 → (5)I8 electronic transitions, respectively, was generated by adjusting the Yb, Tm, and Ho contents in KLu(WO4)2 nanocrystalline samples. Chromaticity coordinates of the emitted white light can be tuned by modifying the excitation power density. The effect of Tm and Ho on the luminescence dynamics has been described by analyzing the upconverted emission intensity dependence on the excitation power, as well as from Stokes and decay time measurements. The effect on upconversion properties of further codoping with Eu in these (Tm, Ho, Yb)-doped KLu(WO4)2 nanocrystals has also been studied.

Channel waveguides on RbTiOPO4 by Cs+ ion exchange.

In this Letter we report Cs(+) ion exchange channel waveguides on RbTiOPO(4) (RTP) for what we believe is the first time. A Ti channel mask was fabricated on an RTP substrate by conventional photolithography. The ion exchange process was carried out in a CsNO(3) melt, and the channels produced ranged from 6 to 11 µm in width. The near-field pattern of the modes was recorded, and type II second harmonic generation in waveguide regime was obtained, producing 512.5 nm green light. The optical characterization shows optical losses of 3.8 dB/cm.

Efficient Type II phase-matching second-harmonic generation in Ba:Yb:Nb:RbTiOPO4/RbTiOPO4 waveguides.

Efficient Type II phase-matching second-harmonic generation of a 1125 nm fundamental beam has been obtained using Ba:Yb:Nb:RbTiOPO(4)/RbTiOPO(4) waveguides grown by liquid phase epitaxy. The refractive indices of the epitaxial layer have been measured at different wavelengths, and the Sellmeier coefficients of the chromatic dispersion curves have been obtained. The phase-matching curve shows that the Ba(2+) doping in RbTiOPO(4) contributes to increase the phase-matching range until 900 nm. The measured effective refractive indices of the propagation modes agree well with the theoretical calculations.

Broad emission band of Yb3+ in the nonlinear Nb:RbTiOPO4 crystal: origin and applications.

By means of micro-structural and optical characterization of the Yb:Nb:RbTiOPO(4) crystal, we demonstrated that the broad emission band of Yb(3+) in these crystals is due to the large splitting of the ytterbium ground state only, and not to a complex multisite occupation by the ytterbium ions in the crystals. We used this broad emission band to demonstrate wide laser tuning range and generation of femtosecond laser pulses. Passive mode-locked laser operation has been realized by using a semiconductor saturable absorber mirror, generating ultra short laser pulses of 155 fs, which were very stable in time, under Ti:sapphire laser pumping at 1053 nm.

Synthesis and characterization of KTiOPO4 nanocrystals and their PMMA nanocomposites.

KTiOPO(4) (KTP) nanocrystals have been synthesized by the modified Pechini method using ethylenediaminetetraacetic acid (EDTA) and ethylene glycol (EG) as chelating and sterification agents, respectively. Orthorhombic KTP has been obtained by calcination at 1073 K for several hours. Differential thermal and thermogravimetric (DTA-TG) analyses have been used to study the optimized heat treatment used on the precursor powder to obtain KTP nanocrystals. X-ray powder diffraction (XRD) studies on the thermally treated precursor powders indicated that nanocrystals began to crystallize at 923 K. Nanocrystals with a size dispersion distribution that fit to a lognormal function centered at 25 nm were observed by electronic microscopy. KTP nanocomposites were prepared by embedding nanocrystals in poly(methyl methacrylate) (PMMA). The photoinduced second-order susceptibility parameter and the piezo-optical coefficient were measured for the KTP nanocomposites. The optimal conditions for the generation of the frequency-doubled second harmonic generation were recorded at 391 K, and at a fundamental laser wavelength of 1064 nm and under additional treatment by polarized UV light, provided the maximum value obtained of 3.23 pm V(-1). The piezo-optical coefficients were recorded at room temperature under photoinduced treatment by a UV laser beam; the maximum value achieved was 0.673 x 10(-14) m(2) N(-1) at a pump-probe delaying time of 160 s.

Coherence length of the KY(WO4)2 single crystal.

Potassium yttrium tungstate is a monoclinic crystal with space group C2/c. The specific X-ray investigations presented in this article determine the coherence scattering length for this crystal. The scattering profiles were obtained using a Philips MRD X-ray diffractometer. The Williamson-Hall method was used to determine the coherence scattering length and internal stresses.

Crystal growth, spectroscopic characterization, and eye-safe laser operation of erbium- and ytterbium-codoped KLu(WO4)2.

Erbium (Er)- and Ytterbium (Yb)-codoped monoclinic KLu(WO4)2 single crystals were grown by top seeded solution growth-slow cooling method for several different doping concentrations. Growth parameters have been optimized to obtain macrodefect-free single crystals. Er energy levels involved in the 4I13/2-->4I15/2 were determined by 6 K polarized optical absorption. The maximum emission cross section for this electronic transition has been evaluated, being 2.85x10(-20) cm2 for E||Nm at 1535 nm. Laser oscillation in the 1.5 microm range was obtained by pumping the Yb ion at 980 nm and sensitizing Er. The maximum output power achieved was 152 mW, with 1.2% slope efficiency.

Isquemia sintomática en accesos vasculares parahemodiálisis / Symptomatic ischemia of hemodialysis vascular access

El objetivo de este estudio es dar a conocer nuestra experiencia en el manejo de pacientes con isquemia sintomática severa asociada a los accesos vasculares para hemodiálisis (AVHD). Entre Enero de 2000 y Junio del 2005 se construyeron 1926 accesos vasculares para hemodiálisis en 1537 pacientes en el Servicio de Cirugía del Hospital Barros Luco Trudeau, seleccionando aquellos pacientes que fueron manejados por presentar elementos de isquemia sintomática severa. El grupo está constituido por 18 pacientes, 9 (50 por ciento) hombres y 9 (50 por ciento) mujeres, 14 (78 por ciento) diabéticos. La edad promedio fue de 61 años. El diagnóstico se hizo en base a la anamnesis, examen físico y laboratorio no invasivo. En algunos casos se realizó eco doppler y angiografía. La incidencia encontrada es 1,17 por ciento, correspondiendo 61,1 por ciento a diabéticos mayores de 60 años y 16,7 por ciento a no diabéticos menores de 60 años (p< 0,05). Se presentó en 1,1 por ciento de los pacientes con AVHD nativo y 1,93 por ciento con AVHD protésico (ns). Las manifestaciones aparecieron en el post operatorio inmediato en 7 (39 por ciento) pacientes y en forma tardía en 11 (61 por ciento). La etiología fue enfermedad arterial oclusiva en 13 casos (72,2 por ciento), mecanismo de robo arterial en 3 (16,7 por ciento) y estenosis funcional en 2 (11,5 por ciento). El manejo consistió en revascularización en 8 casos (44,5 por ciento) y cierre de la fístula mas instalación de catéter tunelizado en 10 (55,5 por ciento). Al término del seguimiento, 15 (83,3 por ciento) presentaban regresión completa de los síntomas y 3 (16,7 por ciento) presentaban secuelas. La isquemia sintomática es una complicación poco frecuente, que puede presentarse tanto en forma precoz como tardía especialmente en pacientes diabéticos mayores de 60 años o con enfermedad vascular periférica, pudiendo significar la pérdida del acceso o dejar secuelas invalidantes. Son importantes las medidas de prevención.

Background: Symptomatic ischemia occurs in 1 to 8 percent of hemodialysis vascular accesses and may result in its loss. Aim: To report our experience in the management of patients with severe symptomatic ischemia associated to a vascular access for hemodialysis. Material and methods: All patients operated for a severe ischemia associated to a hemodialysis vascular access, between 2000 and 2005, were included in this study. Results: Of a total of 1926 vascular accesses, symptomatic ischemia was diagnosed in 18 patients (9 males) aged between 27 and 84 years. Fourteen (78 percent) were diabetic. Thus, the incidence of severe ischemia was 1.2 percent. It appeared in 1.1 percent of native and 1.9 percent of prosthetic vascular accesses. Clinical manifestations appeared in the early postoperative period in seven patients (39 percent). In the rest, they appeared more than 30 days after the procedure. Surgical treatment consisted in revascularization in eight patients (45 percent) and closure of fistula and installation of a tunneled catheter in 10 (55 percent). At the end of follow up, 15 patients (83 percent) had a complete regression of symptoms and three (17 percent) had sequelae. Conclusions: Symptomatic vascular access ischemia occurs in 1.2 percent of procedures, is much more common among diabetics and can be successfully managed in 80 percent of cases.

Growth, spectroscopy and laser operation of Yb:KGd(PO(3))(4) single crystals.

Macrodefect-free single crystals of Yb-doped KGd(PO(3)), a noncentrosymmetric laser host which possesses second-order nonlinear susceptibility, were grown using the top seeded solution growth slow-cooling (TSSG-SC) technique, reaching a maximum ytterbium concentration in the crystal of approximately 3.2x10(20) at/cm(3). In order to evaluate the potential for self-frequency doubling, the dispersion of the refractive indices of KGd(PO(3))(4) was studied and Sellmeier equations were constructed which are valid in the visible and near-infrared. The Stark splitting of the two electronic states of ytterbium was determined from absorption and emission measurements at room and low temperatures, and this allowed to compute the emission cross sections at room temperature. The fluorescence decay time is quite long, 1.22+/-0.01 ms. Laser generation in the 1 mum range is demonstrated with this new Yb host for the first time. Although the maximum output power achieved, of the order of 100 mW, was limited by the available crystal size and doping level, the more than 55% slope efficiency obtained with this first sample is rather promising for the future.

Passively mode-locked Yb:KLu(WO4)2 oscillators.

We demonstrate passive mode locking based on the novel monoclinic double tungstate crystal Yb:KLu(WO4)2. We report the shortest pulses ever produced with an Yb-doped tungstate laser using a semiconductor saturable absorber. A pulse duration of 81 fs has been achieved for an average power of 70 mW at 1046 nm. We compare the performance of the polarization oriented parallel to the Nm- and Np-crystallo-optic axes. Results in the femtosecond and picosecond regime are presented applying either Ti:sapphire or diode laser pumping. The great potential of Yb:KLu(WO4)2 as an active medium for ultrashort pulses is demonstrated for the first time, to our knowledge.