Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study / Elevada heterogeneidad en el diagnóstico y tratamiento a largo plazo en la enfermedad de Wilson: resultados de un estudio multicéntrico español

There is uncertainty regarding Wilson's disease (WD) management. Objectives: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. Methods: Data on WD patients followed at 32 Spanish hospitals were collected. Results: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. Conclusions: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored. (AU)

Existe incertidumbre con respecto al manejo de la enfermedad de Wilson (EW). Objetivos: Evaluar, en un estudio de cohorte retrospectivo español multicéntrico, si el abordaje de la EW es homogéneo entre los centros. Métodos: Se recogieron datos sobre pacientes con EW seguidos en 32 hospitales españoles. Resultados: Un total de 153 casos, 58% hombres, 20,6 años al diagnóstico, 69,1% presentación hepática, fueron seguidos durante 15,5 años. Se objetivaron resultados discordantes en parámetros de laboratorio no invasivos en el 39,8%. La concentración intrahepática de cobre fue patológica en el 82,4%. Las pruebas genéticas solo se realizaron en el 56,6% con resultados positivos en el 83,9%. Un diagnóstico definitivo de EW (puntuación de Leipzig ≥4) se confirmó retrospectivamente en el 92,5% de los casos. Los agentes quelantes fueron la terapia inicial estándar (75,2%) con modificaciones frecuentes (57%), particularmente hacia zinc de mantenimiento. La normalización enzimática no se logró en un tercio, más comúnmente en el contexto de un cumplimiento deficiente, ausencia de mutaciones genéticas y/o presencia de factores de riesgo cardiometabólicos. Aunque sin alcanzar significación estadística, observamos diferencias entre hombres y mujeres en el número de casos, edad en el momento del diagnóstico y la respuesta bioquímica. Conclusiones: De este estudio multicéntrico que incluye centros de referencia pequeños y grandes se desprende una heterogeneidad significativa en el diagnóstico y manejo de los pacientes con EW. La incorporación de pruebas genéticas ha mejorado el diagnóstico. Las diferencias de sexo deben explorarse más a fondo en estudios futuros. (AU)

Spontaneously ruptured hepatocellular carcinoma on non-cirrhotic liver: A prospective case series.

BACKGROUND AND AIMS: Spontaneous ruptured hepatocellular carcinoma is an uncommon complication, and there are scarce data about non-cirrhotic patients. Tumor treatment is not standardized and the risk of peritoneal dissemination is unclear. AIM: we analyzed the treatment and survival in patients with rHCC on non-cirrhotic liver. METHODS: One hundred and forty-one non-cirrhotic patients with hepatocellular carcinoma diagnosed by histology were included in a multicenter prospective registry (2018-2022). Seven of them (5%) presented with hemoperitoneum due to spontaneous rupture. RESULTS: Liver disease was associated in three patients (42.9%). A single nodule was detected in three cases (42.9%). One patient had vascular invasion and none extrahepatic spread. Initial hemostatic therapy and sequential treatment was individualized. Patients with single nodule were treated: resection (one case) with recurrence at 4 months treated with TACE and sorafenib. TACE/TAE followed by surgery (two cases) one in remission 43 months later, the other had liver recurrence at 18 months and was transplanted. Patients with multiple lesions were treated: TAE/emergency surgery and subsequent systemic therapy (two cases), one received lenvatinib (1-year survival) and the other sorafenib (5-month survival). TAE and surgery with subsequent systemic therapy (one case). Initial hemostatic surgery, dying on admission (one case). No patient developed intraperitoneal metastasis. All patients with multiple lesions died by tumor. The 3-year survival rate was 42.9%. CONCLUSIONS: Initial hemostasis was achieved in all patients by TAE/TACE or surgery. Subsequent treatment was individualized, based on tumor characteristics, regardless of rupture. Long-time remission could be achieved in single nodule patients.

Un paciente con fiebre Q en el medio rural / A patient with Q fever in the rural setting

La fiebre Q es una zoonosis poco conocida de distribución global, con una incidencia de 3 casos por cada 100.000 habitantes/año. La principal fuente de contagio son las ovejas, bovinos y caprinos por inhalación de aerosoles de vísceras o materiales contaminados: estiércol, orina, lana, ropa. Un diagnóstico precoz es fundamental para una intervención eficaz, evitando complicaciones crónicas, aquí el papel del médico de atención primaria es clave para lograr este objetivo.(AU)

Q fever is a little-known globally distributed zoonosis, with an incidence of three cases per 100.000 inhabitants/year. The main source of contagion is sheep, cattle and goats by inhalation of aerosols from viscera or contaminated materials: manure, urine, wool or clothing. Early diagnosis is essential for an effective intervention. This avoids chronic complications. The role of the primary care provider is key to attaining this goal.(AU)

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.

Uso de técnicas no farmacológicas para favorecer el estado emocional durante la aplicación del método Ponseti en pacientes pediátricos con pie equino varo congénito en Bogotá, Colombia / Non-pharmacological techniques to improve emotional state while using the Ponseti method in pediatric patients with congenital talipes equinovarus in Bogotá, Colombia

Introducción. Durante la aplicación del método Ponseti (MP), el niño puede mostrar incomodidad, tensión muscular o movimientos corporales que hacen del procedimiento una experiencia desagradable y estresante para pacientes, familiares y personal de salud.Objetivos. Describir los desenlaces de la aplicación de técnicas no farmacológicas (TNF) para el favorecer el estado emocional durante la atención estándar de pacientes con pie equino varo congénito (PEVC) tratados con el MP, el nivel de satisfacción del paciente y su familia con la atención recibida y la calidad de la atención en salud, y evaluar los posibles factores asociados al éxito de la aplicación de las TNF. Metodología. Estudio observacional descriptivo realizado en una cohorte de 21 niños atendidos en una clínica Ponseti de Bogotá (Colombia) entre febrero y noviembre de 2021. Las TNF se aplicaron en dos esquemas diferenciados por los sentidos estimulados. Los datos se describen usando medidas de tendencia central y de dispersión (prueba de Shapiro-Wilk), y la asociación exploratoria entre tener éxito en los esquemas de TNF y las variables se determinó con la prueba de chi-cuadrado (p≥0,05).Resultados. La mediana de edad fue 4,5 meses y el primer esquema de TNF fue exitoso en el 66,67% de los pacientes (97 consultas). El nivel de satisfacción de los cuidadores fue alto (86,07%). El equipo sanitario reportó que el procedimiento fue "extremadamente fácil" o "muy fácil" (86,07%-88,52%). Se identificaron como posibles factores asociados explor-atoriamente al éxito del primer esquema de TNF el sexo, antecedente de tratamiento con MP, y nivel de satisfacción del cuidador con la atención recibida.Conclusión. Las TNF mejoran el estado psicoemocional del niño, facilitando la aplicación del MP y aumentando la satisfacción del cuidador y del equipo sanitario con las sesiones de tratamiento

Introduction: Children may show discomfort, muscle tension or body movements while using the Ponseti method (PM), making the procedure an unpleasant and stressful experience for patients, family members, and health care personnel. Objectives: To describe the outcomes achieved following the use of non-pharmacological techniques (NPT) for emotional support when providing standard care to patients with congenital talipes equinovarus (CTEV) treated with the PM, as well as the level of patient and family satisfaction with the care received and the quality of health care, and to evaluate the possible factors associated with the success of the use of NPT.Methodology: Descriptive observational study conducted in a cohort of 21 children treated in a Ponseti clinic in Bogotá (Colombia) between February and November 2021. NPT were implemented in two schemes differentiated by the senses stimulated. Data are described using measures of central tendency and dispersion (Shapiro-Wilk test), and the exploratory association between having success with the NPT schemes and the variables was determined using the chi-square test (p≥0.05). Results: The median age was 4.5 months, and the first NPT scheme was successful in 66.67% of patients (97 consultations). The level of caregiver satisfaction was high (86.07%). The healthcare team reported that the procedure was "extremely easy" or "very easy" (86.07%-88.52%). Possible factors exploratorily associated with the success of the first NPT scheme were identified as gender, history of treatment with the PM, and level of caregiver satisfaction with the care received.Conclusion: NPT improve the psychoemotional state of the child, facilitating PM implementation, and increasing caregiver and healthcare team satisfaction with the treatment sessions

Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Library searched up to 13 May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. OUTCOME AND MEASURES: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. RESULTS: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. CONCLUSIONS: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. STUDY REGISTRATION: ClinicalTrials.gov NCT04045938.

Modular microring laser cavity sensor.

We propose and experimentally demonstrate a modular microring laser (MML) cavity for sensing applications. The proposed MML permits much more design freedom compared with a traditional simple ring cavity by decoupling the performance parameters into several regions in the cavity. Thus, the different biosensor performance parameters can be optimized semi-independently limiting the need for trade-offs on the design of the biosensing device. The first generation MML has been fabricated and tested. A fiber-to-fiber slope efficiency of up to 1.2%, a temperature coefficient of 1.35 GHz/K and a 3σ limit of detection (LOD) of 3.1 × 10-7 RIU without averaging and 6.0 × 10-8 RIU with a 60 s averaging, has been measured for the MML sensor, which is a record-low LOD in on-chip ring cavity optical sensors. Further optimization is possible, capitalizing on the key advantage of the MML concept, namely the potential for designing the laser cavity to achieve the desired optimization goals.

Clinical Characteristics and Outcome of Drug-Induced Liver Injury in the Older Patients: From the Young-Old to the Oldest-Old.

Older patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥ 65 years) were categorized according to age: "young" (< 65 years); "young-old" (65-74 years); "middle-old" (75-84 years); and "oldest-old" (≥ 85 years). All elderly groups had an increasingly higher comorbidity burden (P < 0.001) and polypharmacy (P < 0.001). There was a relationship between jaundice and hospitalization (P < 0.001), and both were more prevalent in the older age groups, especially in the oldest-old (88% and 69%, respectively), and the DILI episode was more severe (P = 0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin-clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cutoff point for increased odds of cholestatic DILI was 65 years. Older patients had increased non-liver-related mortality (P = 0.030) as shown by the predictive capacity of the Model for End-Stage Liver Disease score (odds ratio (OR) = 1.116; P < 0.001), and comorbidity burden (OR = 4.188; P = 0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs, other than amoxicillin-clavulanate, with increased non-liver-related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.

Redeposition-Free Deep Etching in Small KY(WO4)2 Samples.

KY(WO4)2 is a promising material for on-chip laser sources. Deep etching of small KY(WO4)2 samples in combination with various thin film deposition techniques is desirable for the manufacturing of such devices. There are, however, several difficulties that need to be overcome before deep etching of KY(WO4)2 can be realized in small samples in a reproducible manner. In this paper, we address the problems of (i) edge bead formation when using thick resist on small samples, (ii) sample damage during lithography mask touchdown, (iii) resist reticulation during prolonged argon-based inductively coupled plasma reactive ion etching (ICP-RIE), and (iv) redeposited material on the feature sidewalls. We demonstrate the etching of 6.5 µm deep features and the removal of redeposited material using a wet etch procedure. This process will enable the realization of waveguides both in ion-irradiated KY(WO4)2 as well as thin KY(WO4)2 membranes transferred onto glass substrate by bonding and subsequent polishing.

Lapping and Polishing of Crystalline KY(WO4)2: Toward High Refractive Index Contrast Slab Waveguides.

Rare-earth ion-doped potassium yttrium double tungstate, RE:KY(WO4)2, is a promising candidate for small, power-efficient, on-chip lasers and amplifiers. Thin KY(WO4)2onglass layers with thicknesses ranging between 0.9 and 1.6 m are required to realize on-chip lasers based on high refractive index contrast waveguides operating between 1.55 and 3.00 µm. The crystalline nature of KY(WO4)2 makes the growth of thin, defect-free layers on amorphous glass substrates impossible. Heterogeneous integration is one of the promising approaches to achieve thin KY(WO4)2onglass layers. In this process, crystal samples, with a thickness of 1 mm, are bonded onto a glass substrate and thinned down with an extensive lapping and polishing procedure to the desired final thickness. In this study, a lapping and polishing process for KY(WO4)2 was developed toward the realization of integrated active optical devices in this material.

High index contrast photonic platforms for on-chip Raman spectroscopy.

Nanophotonic waveguide enhanced Raman spectroscopy (NWERS) is a sensing technique that uses a highly confined waveguide mode to excite and collect the Raman scattered signal from molecules in close vicinity of the waveguide. The most important parameters defining the figure of merit of an NWERS sensor include its ability to collect the Raman signal from an analyte, i.e. "the Raman conversion efficiency" and the amount of "Raman background" generated from the guiding material. Here, we compare different photonic integrated circuit (PIC) platforms capable of on-chip Raman sensing in terms of the aforementioned parameters. Among the four photonic platforms under study, tantalum oxide and silicon nitride waveguides exhibit high signal collection efficiency and low Raman background. In contrast, the performance of titania and alumina waveguides suffers from a strong Raman background and a weak signal collection efficiency, respectively.

Al2O3:Yb3+ integrated microdisk laser label-free biosensor.

Whispering gallery mode resonator lasers hold the promise of an ultralow intrinsic limit of detection. However, the widespread use of these devices for biosensing applications has been hindered by the complexity and lack of robustness of the proposed configurations. In this work, we demonstrate biosensing with an integrated microdisk laser. Al2O3doped with Yb3+ was utilized because of its low optical losses as well as its emission in the range 1020-1050 nm, outside the absorption band of water. Single-mode laser emission was obtained at a wavelength of 1024 nm with a linewidth of 250 kHz while the microdisk cavity was submerged in water. A limit of detection of 300 pM (3.6 ng/ml) of the protein rhS100A4 in urine was experimentally demonstrated, showing the potential of the proposed devices for biosensing.

High optical gain in erbium-doped potassium double tungstate channel waveguide amplifiers.

We report on the optical-gain properties of channel waveguides patterned into lattice-matched KGdxLuyEr1-x-y(WO4)2 layers grown onto undoped KY(WO4)2 substrates by liquid phase epitaxy. A systematic investigation of gain is performed for five different Er3+ concentrations in the range of 0.75 to 10at.% and different pump powers and signal wavelengths. In pump-probe-beam experiments, relative internal gain, i.e., signal enhancement minus absorption loss of light propagating in the channel waveguide, is experimentally demonstrated, with a maximum value of 12 ± 5 dB/cm for signals at the peak-emission wavelength of 1534.7 nm.

Factores pronósticos y predictivos en gliomas de alto grado. Experiencia en nuestro centro / Prognostic and predictive factors in high-grade gliomas. Experience at our institution

Objetivo: Describir y analizar los factores predictivos y pronósticos en gliomas de alto grado respecto a supervivencia global (SG) en nuestro centro. Material y método: Desde noviembre drl 2010 hasta agosto del 2014 se incluyó prospectivamente a todos los pacientes diagnosticados de glioma grado III (GIII) o IV (GIV), excepto oligodendrogliomas, oligoastrocitomas e infratentoriales. Todos se trataron con cirugía y quimioradioterapia adyuvante. Análisis estadístico mediante el método de Kaplan-Meier considerando significativo un valor de p ?? 0,05. Resultados: Se estudió a 89 pacientes (18 GIII y 71 GIV). Edad media=60 años; el 55% hombres. El Karnofsky medio fue del 80%. La localización más frecuente (38%) fue frontal. El 65% realizó resección parcial. Se administró quimioterapia completa al 74% y radioterapia completa al 83%. La media de SG fue 26,8±8,3 meses en GIII y 12,5±1 mes en GIV; 72 habían fallecido al terminar el estudio. El 40% de los pacientes tenía MGMT-metilada, el 7% IDH1-mutado y el 47% EGFR-amplificado. Las variables estadísticamente significativas para SG fueron: GIII (p=0,020), edad ?? 70 (p=0,040), ?? 65 (p=0,013) y ?? 60 años (p=0,003), Karnofsky ≥ 70% (p=0,029), resección total (p=0,001), radioterapia completa (p=0,000), MGMT-metilada (p=0,042), IDH1-mutado (p=0,007) y EGFR-no amplificado (p=0,034). Los subgrupos GIII y GIV fueron analizados de manera independiente. En el GIII, el único biomarcador significativo para la SG fue IDH1-mutado y en el GIV la MGMT-metilada (p=0,023). La edad ≥ 70 años es significativa en el GIII (p=0,040) pero no para el GIV (p=0,166). Conclusiones: Los datos están en la línea de estudios anteriores, salvo la edad, que parece no decisiva en el GIV

Objective: To describe and analyse predictive and prognostic factors of overall survival (OS) in high-grade gliomas at our institution. Material and method: All patients diagnosed with grade III (GIII) or grade IV (GIV) gliomas (excluding oligodendrogliomas, oligoastrocytomas or infratentorial gliomas) were prospectively included from November 2010 to August 2014. All were treated with surgery followed by adjuvant radiochemotherapy. The Kaplan-Meier method was used for the statistical analysis, considering a P value ??.05 to be significant. Results: 89 patients were studied (18 GIII and 71 GIV). The average age was 60 years and 55% were men. The mean Karnofsky score was 80%. The most common location was the frontal lobe (38%). A total of 65% were partial resections. Complete chemotherapy was administered to 74% and complete RT to 83% of patients. Mean OS was 26.8±8.3 months for GIII and 12.5±1 month for GIV. 72 had died by the end of this study. A total of 40% of patients had MGMT methylation, 7% IDH1 mutation and 47% EGFR amplification. Statistically significant variables for OS were: GIII (P=.020), age ??70 years (P=.040), ??65 years (P=.013) and ??60 years (P=.003), Karnofsky ≥70% (P=.029), complete radiotherapy (P=.000), complete resection (P=.001), MGMT methylation (P=.042), IDH1 mutation (P=.007) and EGFR non-amplification (P=.034). Additionally, GIII and GIV subgroups were independently analysed. In GIII, the only significant biomarker for OS was IDH1 mutation, while in GIV, MGMT methylation (P=.023) was significant. Age ≥70 years old was a significant factor in the GIII-subgroup (P=.040) but not for GIV (P=.166). Conclusions: Data are in line with previous studies, with the exception of age, which does not appear to be significant in GIV

[Prognostic and predictive factors in high-grade gliomas. Experience at our institution]. / Factores pronósticos y predictivos en gliomas de alto grado. Experiencia en nuestro centro.

OBJECTIVE: To describe and analyse predictive and prognostic factors of overall survival (OS) in high-grade gliomas at our institution. MATERIAL AND METHOD: All patients diagnosed with grade iii (GIII) or grade iv (GIV) gliomas (excluding oligodendrogliomas, oligoastrocytomas or infratentorial gliomas) were prospectively included from November 2010 to August 2014. All were treated with surgery followed by adjuvant radiochemotherapy. The Kaplan-Meier method was used for the statistical analysis, considering a P value ˂.05 to be significant. RESULTS: 89 patients were studied (18 GIII and 71 GIV). The average age was 60 years and 55% were men. The mean Karnofsky score was 80%. The most common location was the frontal lobe (38%). A total of 65% were partial resections. Complete chemotherapy was administered to 74% and complete RT to 83% of patients. Mean OS was 26.8±8.3 months for GIII and 12.5±1 month for GIV. 72 had died by the end of this study. A total of 40% of patients had MGMT methylation, 7% IDH1 mutation and 47% EGFR amplification. Statistically significant variables for OS were: GIII (P=.020), age ˂70 years (P=.040), ˂65 years (P=.013) and ˂60 years (P=.003), Karnofsky ≥70% (P=.029), complete radiotherapy (P=.000), complete resection (P=.001), MGMT methylation (P=.042), IDH1 mutation (P=.007) and EGFR non-amplification (P=.034). Additionally, GIII and GIV subgroups were independently analysed. In GIII, the only significant biomarker for OS was IDH1 mutation, while in GIV, MGMT methylation (P=.023) was significant. Age ≥70 years old was a significant factor in the GIII-subgroup (P=.040) but not for GIV (P=.166). CONCLUSIONS: Data are in line with previous studies, with the exception of age, which does not appear to be significant in GIV.

Low-loss, broadband and high fabrication tolerant vertically tapered optical couplers for monolithic integration of Si3N4 and polymer waveguides.

A low-loss, broadband and high fabrication tolerant optical coupler for the monolithic integration of Si3N4 and polymer waveguides is designed and experimentally demonstrated. The coupler is based on the adiabatic vertical tapering of the Si3N4 waveguides. Low-loss operation is experimentally verified at both 976 and 1460-1635 nm wavelengths. Measured losses per coupler are as low as 0.12 and 0.14 dB at 976 and 1550 nm, respectively, and below 0.2 dB at both wavelengths for lateral misalignments between the Si3N4 and polymer waveguides up to 1.0 µm.

Temperature-dependent absorption and emission of potassium double tungstates with high ytterbium content.

We study the spectroscopic properties of thin films of potassium ytterbium gadolinium double tungstates, KYb0.57Gd0.43(WO4)2, and potassium ytterbium lutetium double tungstates, KYb0.76Lu0.24(WO4)2, specifically at the central absorption line near 981 nm wavelength, which is important for amplifiers and lasers. The absorption cross-section of both thin films is found to be similar to those of bulk potassium rare-earth double tungstates, suggesting that the crystalline layers retain their spectroscopic properties albeit having >50 at.% Yb3+ concentration. The influence of sample temperature is investigated and found to substantially affect the measured absorption cross-section. Since amplifiers and lasers typically operate above room temperature due to pump-induced heating, the temperature dependence of the peak-absorption cross-section of the KYb0.57Gd0.43(WO4)2 is evaluated for the sample being heated from 20 °C to 170 °C, resulting in a measured reduction of peak-absorption cross-section at the transitions near 933 nm and 981 nm by ~40% and ~52%, respectively. It is shown that two effects, the change of Stark-level population and linewidth broadening due to intra-manifold relaxation induced by temperature-dependent electron-phonon interaction, contribute to the observed behavior. The effective emission cross-sections versus temperature have been calculated. Luminescence-decay measurements show no significant dependence of the luminescence lifetime on temperature.