Meningoencephalitis caused by Non-O1, non-O139 Vibrio cholerae in an infant from southern Spain.

Non-O1, non-O139 Vibrio cholerae (NOVC) is an emergent pathogen that mainly causes gastroenteritis. Also, it causes ear, wound infections, and bacteremia but the nervous system is rarely affected. We report on a case of NOVC meningoencephalitis in an infant that recovered after antimicrobial therapy but later presented neurologic sequelae.

Assessment of surface and electrical properties of the TiO2@zeolite hybrid materials.

Degradation of pollutants in aqueous medium is of high interest due to the impact on environment and human health, therefore, design and study of the physico-chemical properties of photocatalysts for water remediation are of major significance. Among properties of photocatalyst, those related to the surface and electrical mechanism are crucial to the photocatalyst´s performance. Here we report the chemical and morphological characteristics of TiO2@zeolite photocatalyst by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) respectively, and a coherent electrical conduction mechanism was proposed based on data obtained from assisted laser impedance spectroscopy (ALIS), in which the zeolite was synthesized from recycled coal fly ash. The results obtained by SEM and XPS verified the presence of spherical particles of TiO2 anatase with presence of Ti3+ state. ALIS results showed that impedance of the entire system increases when the amount of TiO2 increases and the samples with lower capacitive performance allowed a larger transfer of the charges between the solid-liquid interface. All results showed that higher photocatalytic performance of TiO2 growth over hydroxysodalite with 8.7 wt% and 25 wt% of TiO2 can be explained in terms of the morphology of TiO2 and the interactions between substrate-TiO2 mainly.

Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Etiology of avascular necrosis of the hip and shoulder. Screening for Gaucher disease.

INTRODUCTION: Avascular necrosis (AON) of the hip and shoulder is a little studied disease and the predisposing risk factors for its development are not well known. A high percentage of patients are diagnosed with idiopathic osteonecrosis. This study aims to investigate the prevalence of potential etiological factors for AON and to screen for Gaucher disease among patients with idiopathic AON. MATERIAL AND METHODS: This retrospective, single-center, observational study was conducted on patients who had at least one episode of AON of the hip or shoulder at the Hospital de Poniente (Almería, Spain) from January 2010 to December 2019. Clinical and analytical data were collected. Patients whose medical record described no etiological factors for this disease were screened for Gaucher disease. RESULTS: The study sample consisted of 81 patients, of whom 58 were male. The mean age at presentation of AON was 45.9 years. They presented with unilateral hip necrosis (n=43), bilateral hip necrosis (n=34), bilateral hip and unilateral shoulder necrosis (n=3), and unilateral shoulder necrosis (n=1). The most frequent potential etiological factors were smoking (46.9%) and obesity (17.3%). Screening for Gaucher disease was performed in ten patients, all of whom tested negative. CONCLUSIONS: In our study population, the main potential etiological factors the onset of AON of the shoulder or hip were smoking and obesity. A high percentage of patients were diagnosed with idiopathic AON. We believe that a more exhaustive study of less frequent risk factors should be carried out in these cases.

COVID-19 impact on nurses in Spain: a considered opinion survey.

AIM: To survey nurses' opinions about their work conditions at the onset of the COVID-19 pandemic in Spain. BACKGROUND: For the Spanish General Council of Nursing (the Consejo General de Enfermería de España), it was essential to have information on nursing workforce conditions and nurses' preparedness to wear protective measures at the pandemic's onset. The coronavirus outbreak was believed to have started in China and rapidly spread as a global pandemic requiring policies and actions for planning emergency healthcare delivery. METHODS: A cross-sectional survey was conducted online. Data were collected during April 2020 and covered social demography, working conditions, training, availability of personal protective equipment, and nurses' health conditions, including the impact of COVID-19. FINDINGS: From all national territories in Spain, 11 560 registered nurses from different services completed the questionnaire. Findings indicated that the lack of personal protective equipment was a crucial issue, as well as service planning and organization, and 80.2% reported high or very high psychological impact of COVID-19. Alarmingly, 29.5% of the nurses reported COVID-19 symptoms. Of these 23.3% had been tested, and 30.2% were confirmed as being positive to the virus. The nurses deemed proper preparedness for emergencies and disasters as a significant concern. CONCLUSION: Nurses' responses showed evidence of health services deficiencies as a source of damage to their capacity to provide safe patient care and protect themselves and their families' health. The working conditions of the nurses are at critical levels and are unacceptable. The study results provide evidence regarding the necessity of suitable planning and actions being taken to enable safe patient care and safety for nurses. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Our survey gathered nurses' views at the pandemic's onset. The evidence gathered is being used to advise policymakers and nursing organizations to take actions to control public health risks to populations. It is necessary that more investment in growing nursing workforce expertise and health infrastructure for pandemic and epidemic emergencies is provided.

Impact assessment of the incorporation of the rotavirus vaccine in the province of San Luis - Argentina.

Rotavirus (RV) is the main cause of acute gastroenteritis (AGE) in young children. The San Luis province of Argentina introduced RV vaccination in May 2013. We estimate vaccine impact (RVI) using real-world data. Data on all-cause AGE cases and AGE-related hospitalisations for San Luis and the adjacent Mendoza province (control group) were obtained and analysed by interrupted time-series methods. Regardless of the model used for counterfactual predictions, we estimated a reduction in the number of all-cause AGE cases of 20-25% and a reduction in AGE-related hospitalisations of 55-60%. The vaccine impact was similar for each age group considered (<1 year, <2 years and <5 years). RV vaccination was estimated to have reduced direct medical costs in the province by about 4.5 million pesos from May 2013 to December 2014. Similar to previous studies, we found a higher impact of RV vaccination in preventing severe all-cause AGE cases requiring hospitalisation than in preventing all-cases AGE cases presenting for medical care. An assessment of the economic value of RV vaccination could take other benefits into account in addition to the avoided medical costs and the costs of vaccination.

Estimation of the real burden of invasive meningococcal disease in Argentina.

Among the different existing types of bacterial meningitis, the one caused by Neisseria meningitidis is the main presentation of invasive meningococcal disease (IMD). IMD is a significant public health concern and has a reported incidence rate in Argentina of 0.44 cases per 100 000 inhabitants in 2015. However, the actual incidence is thought to be higher as passive surveillance systems neither report nor identify 100% of all cases. The aim of this study is to develop an estimation of the burden of IMD in Argentina closer to reality by adjusting/correcting several limitations observed in the surveillance data available. A retrospective observational study has been performed using four Argentinean national databases recording the number of IMD cases and deaths, serogroups of N. meningitidis and ages, between 2007 to 2016. The reported data were adjusted to account for underreporting and to also integrate the cases missed due to well-known limitations associated with the diagnosis of N. meningitidis detection methods. Data were further analysed by serogroups of N. meningitidis and by age groups. After these adjustments, the potential numbers of IMD cases and IMD-related deaths are estimated to be 3.1 and 1.9 higher than reported, respectively. The study corrects the previous underestimation of the disease burden and provides expectedly more robust estimates aligned with international evidence and highlights the importance of active surveillance, with high-quality methods, for a better definition of preventive strategies against IMD in Argentina.

Ventral tegmental area astrocytes orchestrate avoidance and approach behavior.

The ventral tegmental area (VTA) is a heterogeneous midbrain structure, containing neurons and astrocytes, that coordinates behaviors by integrating activity from numerous afferents. Within neuron-astrocyte networks, astrocytes control signals from distinct afferents in a circuit-specific manner, but whether this capacity scales up to drive motivated behavior has been undetermined. Using genetic and optical dissection strategies we report that VTA astrocytes tune glutamatergic signaling selectively on local inhibitory neurons to drive a functional circuit for learned avoidance. In this circuit, astrocytes facilitate excitation of VTA GABA neurons to increase inhibition of dopamine neurons, eliciting real-time and learned avoidance behavior that is sufficient to impede expression of preference for reward. Loss of one glutamate transporter (GLT-1) from VTA astrocytes selectively blocks these avoidance behaviors and spares preference for reward. Thus, VTA astrocytes selectively regulate excitation of local GABA neurons to drive a distinct avoidance circuit that opposes approach behavior.

Preequilibrium Asymmetries in the

The physical properties of neutrons emitted from neutron-induced fission are fundamental to our understanding of nuclear fission. However, while state-of-the-art fission models still incorporate isotropic fission neutron spectra, it is believed that the preequilibrium prefission component of these spectra is strongly anisotropic. The lack of experimental guidance on this feature has not motivated incorporation of anisotropic neutron spectra in fission models, though any significant anisotropy would impact descriptions of a fissioning system. In the present work, an excess of counts at high energies in the fission neutron spectrum of ^{239}Pu is clearly observed and identified as an excess of the preequilibrium prefission distribution above the postfission neutron spectrum. This excess is separated from the underlying postfission neutron spectrum, and its angular distribution is determined as a function in incident neutron energy and outgoing neutron detection angle. Comparison with neutron scattering models provides the first experimental evidence that the preequilibrium angular distribution is uncorrelated with the fission axis. The results presented here also impact the interpretation of several influential prompt fission neutron spectrum measurements.

[Installed Capacity Perception Survey for the Training of Residents Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico]. / Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte.

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.

INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

Comparative study between Plate-Graff, Plate-Cage and peek cage in cervical spine fusion.

OBJECTIVE: To compare results of Plate-Graff, Plate-Cage and PEEK cage in patients with cervical stenosis. MATERIAL AND METHODS: Prospective, with before and after intervention and comparative study. From January 2005 to October 2011 we included 37 patients (male: 48.6%, female: 51.4%) post-surgery by anterior approach; 3 groups via: Group I, arthrodesis with Plate-Graff n = 12 (M 41.7%, F 58.3%) with 22 levels, group II, Plate-Cage n = 11 (M 63.6% 36.4% F) 19 levels, group III, PEEK cage, n = 14 (M 0% F 50%) with 25 levels. Functional assessment pre- and postoperative with neck disability index (NDI) and visual analogue scale for pain (VAS). The radiological assessment with X-rays only. Descriptive statistics were obtained. Wilcoxon method use according to data distribution, non parametric tests of ranges with sign of Kruskal-Wallis for comparison between more than two groups, and significance level with p 0.05. We used the statistical package SPSS version 15. RESULTS: The majority of patients was found between the sixth and eighth decade of life. At one year of follow up the NDI and pain with VAS shown improvement with statistical difference in three groups (p = 0.001). However, the radiographic measurements per year of follow-up showed a significant improvement of segmental lordosis (p = 0.02) only in patients with Plate-Graff. CONCLUSIONS: Using the graft offers best clinical and radiographic results compared with the Plate Cage and box peek to one year of follow-up.

OBJETIVO: Comparar resultados de placa-injerto, caja-placa y caja-PEEK, en pacientes con conducto cervical estrecho. MATERIAL Y MÉTODOS: Estudio prospectivo, en panel antes y después, de intervención y comparativo. De Enero de 2005 a Octubre de 2011, muestra de 37 pacientes (masculino: 48.6%, femenino: 51.4%) postoperados por vía anterior; formando tres grupos: grupo I, artrodesis con placa-injerto n = 12 (M 41.7%, F 58.3%) con 22 niveles; grupo II, caja-placa n = 11 (M 63.6%, F 36.4%) con 19 niveles; grupo III, caja-PEEK, n = 14 (M 50%, F 50%) con 25 niveles. La evaluación funcional pre- y postoperatoria mediante la escala de discapacidad cervical y escala visual análoga de dolor. La evaluación radiológica con radiografías de columna cervical. Se obtuvo estadística descriptiva. De acuerdo con la distribución de los datos se usaron pruebas no paramétricas de rangos con signo de Wilcoxon, y Kruskal-Wallis para comparación entre más de dos grupos. Con nivel de significancia de p0.05. Se utilizó el paquete estadístico SPSS versión 15. RESULTADOS: La mayoría de los pacientes se encontró entre la sexta y octava década de la vida. Al año de postoperados el índice de discapacidad cervical y mejoría del dolor con EVA mostraron mejoría con diferencia estadística en los tres grupos (p = 0.001). Sin embargo, las mediciones radiográficas al año de seguimiento mostraron una mejoría significativa de la lordosis segmentaria (p = 0.02) sólo en pacientes operados con placa-injerto. CONCLUSIONES: El uso de la placa-injerto ofrece mejores resultados clínicos y radiográficos en comparación con la caja-placa y caja-PEEK, al año de seguimiento.

Diagnosing slipped capital femoral epiphysis amongst various medical specialists.

PURPOSE: To evaluate sensitivity, specificity and accuracy of a radiographic slipped capital femoral epiphysis (SCFE)-diagnosis among medical specialists. METHODS: Three paediatricians, three paediatric radiologists and three paediatric orthopaedic surgeons completed two rounds of a survey of anteroposterior and frog-leg lateral radiographs of patients with a diagnosis of SCFE (25), femoroacetabular impingement (four), Legg-Calvé-Perthes (11) or no hip pathology (ten). Intra- and interobserver agreement among specialties regarding the diagnosis of a SCFE were assessed using Cohen's kappa coefficient (κ). Diagnostic accuracy of SCFE relative to the benchmark, a combination of the radiographic diagnosis based on Klein's line, clinical symptoms and surgical treatment, was assessed computing sensitivity, specificity and accuracy. RESULTS: Intraobserver agreement between the surveys was moderate among paediatricians (κ-range, 0.44 to 0.52), moderate to almost perfect among orthopaedic surgeons (κ-range, 0.79 to 0.88) and almost perfect among paediatric radiologists (κ-range, 0.83 to 1.00). Interobserver agreement for survey 1 and 2 was slight among paediatricians (mean κ, 0.19), substantial among orthopaedic surgeons (mean κ, 0.77) and almost perfect among paediatric radiologists (mean κ, 0.86). Sensitivity of SCFE-diagnosis was high among radiologists and orthopaedic surgeons (88% to 100% for both specialties), but lower for paediatricians (24% to 76%). Specificity was high among radiologists and orthopaedic surgeons (72% to 84%), however, variable among paediatricians (56% to 80%). Accuracy of a SCFE-diagnosis was highest in radiologists (84% to 92%), followed by orthopaedic surgeons (80% to 88%) and paediatricians (48% to 78%). CONCLUSION: SCFE can be detected on radiographs by different medical specialties. Intra- and interobserver agreement, specificity, sensitivity and accuracy for radiographic SCFE-diagnosis amongst paediatric radiologists and orthopaedic surgeons are better than that of general paediatricians. LEVEL OF EVIDENCE: II.

Effects of Mn supplementation in late-gestating and lactating red deer (Cervus elaphus hispanicus) on milk production, milk composition, and calf growth.

This study describes the effects of Mn supplementation of 20 late-gestating and lactating Iberian red deer (Cervus elaphus hispanicus) females (hinds) fed a balanced diet on milk production and milk composition over the lactation period. Body weight of their calves at birth and at weaning was also evaluated. In addition, the effect of lactation stage was studied. For these purposes, 2 groups of hinds, one composed by 12 individuals (experimental) and the other by 8 individuals (control) were compared. Experimental hinds were s.c. injected weekly with Mn (2 mg Mn/kg BW) from day 140 of gestation until the end of lactation (week 18; forced weaning by physical separation). Control hinds were injected with a physiological saline solution with the same volume and at the same frequency as the experimental group. Serum Mn content of hinds was assessed just before the first Mn injection and at week 10 of lactation to assess whether the injected Mn increased Mn concentrations in blood. No differences were observed for BW of calves at birth but calves whose mothers were injected with Mn tended (P = 0.07) to have greater gain of BW from birth to weaning in proportion of BW at birth compared to calves from control hinds. In addition, supplementation with Mn increased (P ≤ 0.05) daily milk production by 10.2%, milk fat content by 11.2%, and total fat yield by 17.8%. Also, milk from hinds supplemented with Mn had more Ca (P < 0.001) and P (P < 0.05) than milk from control hinds. Manganese supplementation did not influence Mn serum content when blood was analyzed at week 10 of lactation, but increased the Mn content of milk by 18.3% (P < 0.001). Lactation stage affected (P < 0.001) fat, protein, lactose, and DM. Their contents increased as lactation proceeded, and protein was substituted by fat. Therefore, results suggest that Mn supplementation of hinds is recommended, even when they are fed a balanced diet, to increase milk production and the content of fat, Ca, P, and Mn of milk.

Clinical and epidemiological characteristics of intestinal parasite infection by Blastocystis hominis. / Características clínicas y epidemiológicas de la parasitación intestinal por Blastocystis hominis.

OBJECTIVES: Blastocystis hominis (B. hominis) is one of the most common intestinal parasites isolated in humans. The parasite can cause gastrointestinal symptoms or, in most cases, remain asymptomatic. There are issues concerning the parasite's pathogenic character. The aim of this study was to analyse the clinical and epidemiological characteristics of the parasite infection by B. hominis, with or without other parasitic co-infections. PATIENTS AND METHODS: An observational retrospective study was conducted of B. hominis isolates in faeces from October 2004 to March 2016 in a tropical medicine unit. We reviewed all patients with a parasite infection, exclusively or not by B. hominis. RESULTS: We studied 3070 patients, 570 (18%) of whom were diagnosed with B. hominis infection, which was the only isolate in 245 (43%) of the 570 patients. A total of 325 (57%) patients presented other parasitic co-infections (Entamoeba histolytic or Entamoeba dispar, Strongyloides stercoralis, hookworm and Schistosoma spp.). The main symptom was abdominal pain (41.8%). In 31.2% of cases, the parasite was detected in the imported diseases screening of asymptomatic patients. Of those who underwent treatment with metronidazole, 78.2% improved. The parasite was neutralised in 82.6% of the patients. CONCLUSIONS: Parasite infection by B. hominis is one of the most common diseases in our tropical medicine unit. Most patients are asymptomatic, or their symptoms can be attributed to other parasite infections. In those cases in which symptoms persist without being able to attribute them to other causes, a specific treatment is recommended.

Lithospheric folding by flexural slip in subduction zones as source for reverse fault intraslab earthquakes.

Subduction requires the permanent generation of a bend fold in the subducting slab which mechanics is not well understood. Lithospheric bending of subducting slabs was traditionally considered to be accommodated by orthogonal flexure, generating extensional outer rise earthquakes responsible of the external arc elongation during folding. Here we explore the possibility of lithospheric flexure being accommodated through simple shear deformation parallel to the slab (folding by flexural slip) and evaluate this process as source of earthquakes. The seismicity predicted by flexural slip dominated slab bending explains a significant amount of intermediate earthquakes observed in subduction zones with different degrees of coupling. This mechanism predicts the generation of intraslab thrust earthquakes with fault planes subparallel to the slab top. Being the orientations of the fault planes the same for the interface thrust earthquakes and the flexural-slip intraslab earthquakes, the amount of seismic moment liberated by the interface could be significantly lower than considered before. This proposed seismic source should be taken into account in models and hazard studies of subduction zones. Determining the seismic generating processes in subduction zones and their characteristics is a fundamental issue for the correct assessment of the associated seismic and tsunami risk.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

Numerical modeling of fiber specklegram sensors by using finite element method (FEM).

Although experimental advances in the implementation and characterization of fiber speckle sensor have been reported, a suitable model to interpret the speckle-pattern variation under perturbation is desirable but very challenging to be developed due to the various factors influencing the speckle pattern. In this work, a new methodology based on the finite element method (FEM) for modeling and optimizing fiber specklegram sensors (FSSs) is proposed. The numerical method allows computational visualization and quantification, in near field, of changes of a step multi-mode fiber (SMMF) specklegram, due to the application of a uniformly distributed force line (UDFL). In turn, the local modifications of the fiber speckle produce changes in the optical power captured by a step single-mode fiber (SSMF) located just at the output end of the SMMF, causing a filtering effect that explains the operation of the FSSs. For each external force, the stress distribution and the propagations modes supported by the SMMF are calculated numerically by means of FEM. Then, those modes are vectorially superposed to reconstruct each perturbed fiber specklegram. Finally, the performance of the sensing mechanism is evaluated for different radius of the filtering SSMF and force-gauges, what evidences design criteria for these kinds of measuring systems. Results are in agreement with those theoretical and experimental ones previously reported.