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Aim: To analyze the frequency and variables related to inappropriate rivaroxaban dosage in clinical practice and its impact on outcomes after 2 years. Materials & methods: Postauthorization, observational, multicenter study, in which atrial fibrillation patients, treated with rivaroxaban ≥6 months were included. Results: A total of 1421 patients (74.2 ± 9.7 years, CHA 2 DS 2 -VASc 3.5 ± 1.6) were included. Overall, 22.9% received rivaroxaban 15 mg. The proper dose of rivaroxaban was taken by 83.3% (9.7% underdosed, 7.0% overdosed). Older age and renal insufficiency were associated with inadequate rivaroxaban dosage. There was a trend toward higher all-cause mortality among underdosed patients (adjusted hazard ratio 1.39; 95% CI 0.75–2.58), and more bleedings in overdosed patients (2.29 vs 0.80 events/100 patient-years; p = 0.14). Conclusion: In clinical practice, rivaroxaban is properly dosed in most patients.

Nanocomposite engineering of biosensors, biomaterials, and flexible electronics demand a highly tunable synthesis of precursor materials to achieve enhanced or desired properties. However, this process remains limited due to the need for proper synthesis-property strategies. Herein, we report on the ability to synthesize chitosan-gold nanocomposite thin films (CS/AuNP) with tunable properties by chemically reducing HAuCl

Background Coronavirus disease 2019 is a systemic entity, where cardiac involvement has been described. The echocardiogram is a diagnostic tool that describes myocardial damage with good certainty. Objectives Determine which echocardiographic parameters are predictors of mortality. Analyze if there is a difference in clinical, laboratory and echocardiographic variables in terms of patients who died versus those who survived. Investigate the cut-off point of the echocardiographic parameters that is best associated with mortality. Methods Prospective, analytical, comparative study. Patients admitted to the hospital with Coronavirus 2019 infection. Clinical, laboratory and echocardiographic variables will be assessed. The association with three-month mortality of the different variables will be determined. We used ROC-curves for the best cut-off associated with mortality. The association with three-month mortality was analized using Cox regression, unadjusted analysis of the variables was performed, as well as adjusted analysis for age and gender. Results 84 patients were included, a mortality of 29% was documented. Significant differences were found in the left atrial volumen index, the E/e', the proportion of dilatation of the right ventricle and diastolic dysfunction. Tricuspid annulus anterior systolic excursion (TAPSE), pulmonary artery acceleration time (PAA), tricuspid regurgitation velocity (TRV), pulmonary artery systolic pressure (PASP), left ventricular longitudinal strain (LVGLS), of the left atrium (LAGLS) and the right ventricular free wall longitudinal strain (RVFWLS). Right ventricular dilation, right ventricular shortening fraction, TAPSE, PASP, TRV, LVGLS, LAGLS, and RVFWLS were associated with mortality. Conclusion Right ventricular dilation, right ventricular shortening fraction, TAPSE, PASP, TRV, LVGLS, LAGLS, and RVFWLS are the echocardiographic parameters that were associated with three-month mortality. Funding Acknowledgement Type of funding sources: None. Table 2

SP is funded by the Royal Society. This work was supported by an Action Medical Research Action/The Chief Scientist Office (CSO), Scotland grant (GN2614) and a Cunningham Trust grant to SP and SJP. Support to the analysis was provided by the St Andrews Bioinformatics Unit funded by the Wellcome Trust [grant 105621/Z/14/Z]. Assessment of the Aston cohort was supported by funding from The Waterloo Foundation to JBT and SP [797–1720]. Analysis of the discovery pedigree was supported by the University of Kansas grant (NIH:NIDCD 5 R01 DC001803). Analysis of the York cohort was funded by Wellcome Trust Programme Grant 082036/B/07/Z. DFN is currently supported by Oxford Brookes University funds, the Leverhulme Trust and the British Academy. This work was, in part, completed while DFN was at the Wellcome Trust Centre for Human Genetics, Oxford as an MRC Career Development Fellow (G1000569/1). We would like to thank the members of all teams who collected the data and the families who participated. At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N = 360) compared to cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N = 42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N = 1825; minimum p = 0.002 for nonword reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level. Publisher PDF

Background: The phase III Monaleesa-2, Monaleesa-3 and Monaleesa-7 trials have shown significantly improved PFS for the combination ribociclib + ET vs ET + placebo in pre-, peri-, and postmenopausal women with HR+/HER2–, first and second line aBC. The Compleement-1 trial is a phase IIIb, single-arm, open-label, international study to assess the safety and efficacy of ribociclib + letrozole in men and women who have not received prior ET for HR+, HER2– ABC [J Clin Oncol 36, 2018 (suppl; abstr 1056)]. Methods: 526 patients with HR+, HER2– ABC, ≤1 line of prior CT, and no prior ET for aBC were enrolled in the Compleement-1trial in Spain from April 2017 to January 2018. Patients received ribociclib (600 mg/day, 3 weeks on/1 week off) + letrozole (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6 mg subcutaneous implant every 28 days). The primary objective was safety and tolerability. Here we report on a sub-analysis from the Spanish population of Compleement-1 trial including baseline characteristics and early safety results for the first patients enrolled who completed at least 56 days of follow-up or discontinued before the cut-off date (3rd Oct 2017). Results: One hundred fifty four patients constituted the analytical cohort for this sub-analysis. Demographics and baseline characteristics: median age was 52 years (range 24-82); 1% of patients were male, 31.8% female pre-menopausal and 67.5% female post-menopausal; 44.2% vs 38.3% of patients had visceral disease vs bone only disease; 49.9% patients had ≥2 metastatic sites; and 34.4% of patients presented as de novo stage IV. The median exposure for study treatment was 1.8 months (range 0.8-1.8). The grade 3/4 events reported >1% included neutropenia (50%), increased GGT levels (3.2%), leukopenia (1.3%), and increased ALT (1.3%). QTcF prolongation >480ms based on ECG data was reported in 1.2% patients. Median dose intensity for ribociclib was 600mg/day (range 476.5-600); 11% of patients required one dose reduction (8.4% due to AEs), 59.7% had at least one dose interruption (57.1% due to AEs) and 9.7% were permanently discontinued (4.5% due to AEs). Conclusions: Preliminary safety results from this Compleement-1 sub-analysis including Spanish population are consistent with previous data presented from Monaleesa-2, Monaleesa-3, Monaleesa-7 and Compleement-1. These data support the predictable and manageable safety profile of ribociclib in combination with letrozole. Clinical trial information: NCT02941926 Citation Format: Salvador J, Ciruelos EM, Prat A, Jiménez-Rodríguez B, de la Cruz L, Martínez N, Villanueva Vázquez R, de Toro R, Antón A, Moreno F, Alvarez I, Gavila J, Quiroga V, Vicente E, de la Haba J, González-Santiago S, Díaz N, Barnadas A, Cantos Sánchez de Ibargüen B, Delgado JI, Bellet M, Gimeno A, Sanz S, Martin M. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC) with no prior endocrine therapy (ET) for ABC: CompLEEment-1 trial, preliminary results from Spanish population [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-17.

We report efficient high harmonic generation and control in glass devices fabricated by femtosecond laser micromachining. This work paves the way to microfluidic HHG beamlines for X-ray spectroscopy with attosecond resolution.

We demonstrate efficient high-order harmonic generation in fused-silica chips fabricated by femtosecond laser micromachining. This work provides a route toward the miniaturization of HHG beamlines and the implementation of X-ray spectroscopy with attosecond temporal resolution.

We report efficient high harmonic generation and control in glass chips fabricated by femtosecond laser micromachining. This work paves the way for the implementation of microfluidic HHG beamlines for X-ray spectroscopy with attosecond resolution.

We demonstrate efficient high-order harmonic generation in fused-silica chips fabricated by femtosecond laser micromachining. This work provides a route toward the miniaturization of HHG beamlines and the implementation of X-ray spectroscopy with attosecond temporal resolution.

Prostate cancer (PCa) is the second leading cause of cancer deaths in the United States alone. An emerging area of cancer therapeutics is the combination of the standard-of-care treatment with natural products. Andrographolide, a labdane diterpenoid and the main bioactive component of the medicinal plant Andrographis paniculata, has shown a wide range of therapeutic potential, including cancer. Previous studies from our laboratory have demonstrated that Andrographolide induces a DNA damage response, including ATM gene upregulation, involving cell growth suppression, cell cycle arrest, and apoptosis in PCa in vitro. The ATM gene is an important regulator of p53 and is consider a master switch for the p53-family member p63. The p63 is a natural marker of the basal lamina in the normal prostate, while its expression is lost in 99% of prostatic adenocarcinomas. Like p53, the p63 protein is implicated in tumor suppression and inhibition of metastasis, and also plays a role in energy metabolism. In this study, we aim to (1) determine the role of Andrographolide on the expression of p63, and (2) determine the bioenergetics profile of PCa cells. Androgen-dependent (22Rv1) and androgen-independent (PC3) PCa cell lines were treated with Andrographolide (25µM) for 24 h and 48 h. The gene expression of TP63 was assessed by real-time quantitative PCR (RT-qPCR). At the protein level, the expression of p63 was evaluated by immunofluorescence. The bioenergetics profile was performed using the Agilent Seahorse XF Real-Time ATP Rate Assay to determine the ATP production from glycolysis and mitochondria in living PC3 and 22Rv1 PCa cells. RT-PCR analysis showed a significant upregulation of the TP63 gene with a fold-change of 2.2 (p< 0.05) and immunofluorescence analysis showed an increase in expression of p63 protein with a fold-change of 1.8 (p< 0.05) in 22Rv1 cells treated with Andrographolide. The bioenergetics profile of PC3 cells, 48 h after Andrographolide treatment, revealed a shift in the cytoplasmic to mitochondrial ATP production rate from 54.4% to 72.6% and from 45.6% to 27.4%, respectively. Similar results were obtained in 22Rv1 cells. These results confirmed that Andrographolide induces the expression of the tumor protein p63 in androgen-dependent 22Rv1 PCa cells and alters the bioenergetics profile of both PC3 and 22Rv1 PCa cells. Our findings suggest a novel mechanism in which Andrographolide promotes the expression of p63 as in normal cells, and transforms the bioenergetics by increasing glycolytic-ATP. Citation Format: Jesus Sosa, María Sánchez Vázquez, Sylvette Ayala-Peña, Carlos Torres Ramos, Magaly Martínez Ferrer. Altered bioenergetics profile in prostate cancer cells treated with andrographolide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2459.

Recycling systems are a challenging problem from the control viewpoint due to their detrimental effects. This paper proposes a simple way to stabilize and control a class of high-order recycling systems with time delays, internal instability and possible complex conjugate poles. The strategy proposes P / PI / PD / PID -like delayed controllers. Conditions to guarantee the stability of the controlled closed-loop system are stated. The performance of the proposed strategy is illustrated by numerical simulation.

Highlights • Intimal sarcoma is an extremely rare group. • Intimal sarcoma of large veins even rarer information and case reports are limited. • Unique case in the medical literature and the best current evidence in the biological behavior and the response of the multiple options of treatment in this type of tumors., Introduction Intimal sarcoma is an extremely rare group of undifferentiated pleomorphic sarcoma arising from the intimal layer of vessels accounting for only 1% of all sarcomas, intimal sarcoma of large veins are even less common. Cases presentation We present two cases of intima sarcoma, one originated form the basilar vein and the other from the cephalic vein, the first one was treated with surgery and postoperative chemotherapy followed by Radiotherapy (RT), the second case was treated with isolated limb perfusion followed by marginal resection and RT. Both patients progressed to the lungs in a short time, the first case was treated with metastasectomy of the lung and is without evidence of disease 7 months after surgery; the second case treated with isolated limb perfusion has stable disease. Discussion Intimal sarcoma are very aggressive tumors, with a high metastatic potential, the two patients progressed to lung in a short time (2 months) after local treatment. Both cases exhibit good response to chemotherapy and metastasectomy with a disease – free period of 7 months. Conclusion We propose that given the aggressive behavior of these tumors, they should be treated with chemoradiotherapy postoperative, either by systemic chemotherapy or isolated limb perfusion for the limp sparing surgery in this histology.

There is a growing need for scientific studies and tools that allow the evaluation of the effects at an affective level of some non-pharmacological therapies for people with dementia such as the creative therapeutic dance.To explore the validity and reliability of the Profile of Mood States (POMS) in people with dementia and to analyse the possible differences in the scores of the participants before and after sessions of creative therapeutic dance.POMS was administered to 36 people with dementia before and after four group sessions of creative therapeutic dance. To verify the construct validity, PANAS and STAXI-2 were also administered.The POMS presented a good internal consistency for each factor and an excellent one for the total scale. The temporal stability was medium-high. Convergent validity results support construct validity. After the creative therapeutic dance sessions, POMS factors tension, depression and confusion were reduced, while vigour increased significantly. There was no effect on fatigue and anger.The validity and reliability of POMS have been demonstrated in a population with dementia. Creative therapeutic dance can offer emotional benefits for people with dementia.Propiedades psicometricas del Profile of Mood States (POMS) en personas con demencia y su aplicacion en la evaluacion de los efectos de la danza creativa terapeutica.Introduccion. Existe una creciente necesidad de estudios cientificos e instrumentos que permitan evaluar los efectos en el plano afectivo de algunas terapias no farmacologicas para personas con demencia, como la danza creativa terapeutica. Objetivos. Determinar la validez y fiabilidad del Profile of Mood States (POMS) en personas con demencia y analizar las posibles diferencias en las puntuaciones de los participantes antes y despues de sesiones de danza creativa terapeutica. Pacientes y metodos. El POMS se administro a 36 personas con demencia antes y despues de cuatro sesiones grupales de danza creativa terapeutica. Para comprobar la validez de constructo se administraron dos cuestionarios autoinformados (PANAS y STAXI-2). Resultados. El POMS presento una buena consistencia interna para cada factor y excelente para la escala total. La estabilidad temporal fue media-alta. Los resultados de validez convergente apoyan la validez de constructo. Despues de las sesiones de danza creativa terapeutica, los factores tension, depresion y confusion del POMS se redujeron, mientras que el factor vigor aumento significativamente. No hubo ningun efecto sobre la fatiga y la colera. Conclusiones. Se ha demostrado la validez y fiabilidad del POMS en una poblacion con demencia. La danza creativa terapeutica puede ofrecer beneficios emocionales para personas con demencia.

Whispering gallery mode (WGM) resonators are promising optical structures for microfluidic label-free bio-sensors mainly due to their high sensitivity, but from a practical point of view they present numerous constraints that make their use in real laboratory diagnosis application difficult. Herein we report on a monolithic lab on a chip fabricated by a hybrid femtosecond laser micromachining approach, for label-free biosensing. It consists of a polymer WGM microresonator sensor integrated inside a glass microfluidic chip, presenting a refractive index change sensitivity of 61 nm per RIU. The biosensing capabilities of the device have been demonstrated by exploiting the biotin-streptavidin binding affinity, obtaining a measurable minimum surface density increase of 67 x 10(3) molecules per mu m(2).

Background Benefit derived from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients (pt) with hormone-receptor–positive HER2 negative early breast cancer. The 21-gene recurrence-score (RS) assay Oncotype DX, provide prognostic and predictive information. Results of the TAYLORx study have confirmed that most of patients with negative node status and RS > 25 can avoid CT without increasing their risk of relapse. However, pt 20 showed benefit with CT. Methods Aim: To analyse the impact of age using RS test to change the indication of adjuvant CT and the relationship between different clinical pathological factors and the RS value. We analysed 240 cases out of 251 RS test performed in the 3 ICO Centers during 2017-2018. We compared the adjuvant treatment initially planned according to institutional protocol with the treatment given after RS in the total cohort and in pt Results CT was indicated in all pt before knowing the RS results. Only 46 pt (19%) received CT after RS results. 14 out of 88 pt 25 ( 25 in a multivariate analysis. Table . 209P Age median (range) 53 (19-76) Tumor size median 15 mm Histological grade G1 23% G2 69.7% G3 4.4% Progesterone receptor ≤20% 21% >20% 78% Ki67 median (p25-75) 20 (13,28) ≤14 27% 14-25 41% >25% 31% Nodal status pN0 57% pN1mic 15% pN1a 27% Conclusions 82% of pt of our series could avoid CT, however this proportion change after TAYLORx results in younger patients. Today 75% of these pt would had avoided CT. Ki67 > 25% and Progesterone Receptor ≤20% were the only pathological factors associated with an increased risk of RS > 25. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

In this paper we consider a quantum waveguide that consists of three strata ∏0 = {(x, x 3) ∈ ℝ3 : x 3 < 0}, ∏0,h = {(x, x 3) ∈ ℝ3 : 0 < x 3 < h }, ∏ h = {(x, x 3) ∈ ℝ3 : x 3 > h }, where x = (x 1, x 2) ∈ ℝ2. A potential of the form q = qr + qs is established in this structure, where qr is a regular bounded potential depending on only the coordinate x 3, and qs is the singular potential qs = α 1 δ (x 3) + β 1 δ´ (x 3) + α 2 δ (x 3 – h) + β 2 δ´ (x 3 – h) with support at the planes x 3 = 0 and x 3 = h. The Green’s function of the waveguide is constructed as an expansion involving the eigenfunctions and generalized eigenfunctions of an auxiliary one-dimensional Schrödinger operator. The asymptotic analysis of the Green’s function is carried out by means of the stationary phase method. This gives the leading contribution of the Green’s function far from the point source. Finally some numerical examples are considered for the application of the present analysis.

Background Haemophilia is an X-linked hereditary bleeding disorder caused by deficiency in coagulation factor VIII (FVIII), in haemophilia A (HA), and factor IX in haemophilia B (HB). They are classified as severe, moderate or mild, depending on the level of coagulation factor deficiency. Men are affected clinically by the disease, and women, who are carriers, usually remain asymptomatic. HA is more common than HB (from 80% to 85% of all cases). Their bleeding complications primarily affect the musculoskeletal system. Hemarthrosis is the major hemophilia-related complication, responsible for a particularly debilitating chronic arthropathy, in the long term, affecting mainly the load joints (knees, ankles and elbows). In addition to clotting factor concentrates, usually prescribed by the haematologist, The management of acute hemarthrosis and chronic arthropathy requires a close collaboration with rheumatologists. This collaboration is the key to effectively preventing hemarthrosis, managing acute joint bleeding episodes, assessing joint function, and actively treating chronic arthropathy. Objectives To analyse the clinical characteristics, extent of joint involvement and associated comorbidity of a cohort of patients with hemophilic arthropathy. Methods This is a retrospective study, carried out in the Haemophilia Unit of our hospital (regional reference), in patients with moderate to severe haemophilia A and B, with hemophilic arthropathy, seen in consultation with episodes of joint bleeding (2007–2017). Severity of haemophilia was defined based on determined by the percentage of FC activity (VIII and IX), moderate from 1% to 5%, severe Results We included 88 patients (87 men and 1 symptomatic carrier woman with decreased levels of factor VIII), mean age 31±17 years. HA (severe 56%, moderate 26%), HB (severe 14%, moderate 1%). The target joint: knee 51%, followed by ankle 26%, elbow 13% and other 7% (5 shoulders and 2 wrists). In 61 patients, magnetic resonance imaging (MRI) was performed: synovial hypertrophy 9%, hemosiderin deposits (in acute stage of joint bleeding) 2% and structural alteration (erosions and subchondral cysts, loss of focal cartilage) 68%. A radioisotope synoviorthesis was made to 18 patients: 12 with sulfide 186 Re colloidal (5 ankles, 4 knees, 2 elbows) and 6 with 90 Y colidal citrate (4 knees, 3 ankles), having a decrease of 74% (range 59%–100%) in the number of hemarthrosis in the 3 subsequent months. Total knee replacement was needed in 13% of the patients (7 with HCV liver disease and in 6 HCV liver disease and coexistence with HIV). They have infection due to HCV 33%, HIV 25% and HBV 6%. Conclusions This study highlights the extent of joint damage in haemophiliac patients as well as the high comorbidity of HCV and HIV infections. The experience of a monographic Haemophilia consultation, with the participation of different specialties (being fundamental the rheumatologist), benefits the multidisciplinary approach of these patients, being the results obtained in our series concordant with the described in the literature. Disclosure of Interest None declared

Background In patients with haemophilia, the development of inhibitors to factor VIII/IX (Haemophilia A and B, HA/HB), prevents adequate replacement therapy and results in increased risk of serious bleeding episodes, poor control of joint bleeding, and progressive, debilitating joint disease. Objectives To describe, according to the Arnold-Hilgartner scale (AHRS), the radiological findings in a cohort of hemophilic arthropathy (HArth) patients and to analyse the relationship that may exist between the degree of joint involvement and HA/HB, severity, age and presence or absence of inhibitor. Methods This is a retrospective study, carried out in the Haemophilia Unit of our hospital, in patients with HArth (2007–2017). Severity of haemophilia: percentage of coagulation factor (CF) activity, moderate (1%–5%) and severe For the study of the association of the type and degree of haemophilia; and the presence of inhibitor, with the level in the AHRS, a linear model was used. The significance in this regard of the linear contrasts of interest was studied using F tests, defining the first species error at 0.05. Results We included 88 patients. Characteristics of the patients in the attached chart. No significant association was detected between the type and severity of haemophilia with the development of inhibitor. The results of the linear model only showed association (p=0.01) between the severity of haemophilia and AHRS, patients with moderate haemophilia presented a least square mean for the AHRS of 2.6 (0.3), whereas the serious ones had a value of 3.4 (0.2). The least squared means for patients with HA and HB were 2.9 (0.2) and 3.1 (0.4) respectively, the contrast did not reach statistical significance (p>0.1), and the same occurred between patients who had generated or not inhibitor 2.8 (0.2) Vs 3.1 (0.3). Apart from the severity of haemophilia, the other factor that showed a significant and significant effect (p Conclusions Contrary to what has been observed in other studies, in our cohort it does not seem that the presence of inhibitor or the type of haemophilia has a negative effect on the severity of the radiological findings. The age and severity of haemophilia do seem to influence the radiological stage. Disclosure of Interest None declared

Background The greater morbidity of the patient with haemophilia is due to hemarthrosis. The treatment is based on the administration of deficient coagulation factor (FC). The treatment is divided into prophylactic (TP) and on demand (AD). Prophylaxis consists in the administration of FC in order to maintain adequate levels of factor to prevent or reduce spontaneous bleeding and AD is the application of the factor when there is clinical evidence of bleeding. The TP is the recommended treatment in severe haemophilia, plasma and recombinant concentrates are used, safe and effective, but with a short half-life, which requires frequent intravenous infusions, being a barrier to compliance. Another drawback of the current treatment in haemophilia A (HA) is that up to 30% develop inhibitor (antibodies that neutralise the activity of a CF). New subcutaneous drugs (NSD) have begun to be used in clinical trials, such as: Emicizumab: Bispecific anti–IXa/X monoclonal antibody. Concizumab: Anti–TFPI antibody. This new therapeutic strategy can have implications both from a clinical and economic point of view. Objectives To analyse the different treatment regimens and their economic implications in a cohort of patients with hemophilic arthropathy (HA). Evolution of hemarthroses in patients with AH after starting treatment with NSD in the clinical trial phase. Methods Retrospective descriptive study, in the Haemophilia Unit of our hospital(regional reference), in patients with AH (Haemophilia A and moderate-severe B), followed in consultation with episodes of joint bleeding, from January 2007 to October 2017. Gravity of the haemophilia determined by the percentage of FC activity (VIII and IX), moderate from 1% to 5%, severe Results We included 89 patients (88 men and 1 carrier woman), mean age 31±17 years, HA (severe 56%, moderate 26%), HB (severe 15%, moderate 1%). 17% develop inhibitor (10 severe HA, 3 moderate HA, 3 severe HB). Treatment on demand 44% and prophylaxis 38%. Replacement therapy: FC VIII (44% severe HA, 22% moderate HA), FC IX (11% severe HB, 1% moderate HB), recombinant active factor VII (rFVIIa) (2 patients with severe HB with inhibitor). In treatment with monoclonal antibody (patients currently in Clinical Trial): 15% Emicizumab, of these 4 are with inhibitor (2 severe HA, 1 moderate HA, 1 severe HB and 1% Concizumab (severe 1HB with inhibitor). The number of hemarthros was analysed 1 year before the administration of NFS until now, achieving a statistically significant reduction in the rate of joint bleeding of 86% (p Conclusions The majority of patients with severe and moderate haemophilia are on demand treatment, despite existing recommendations. It can also be said that there are drugs in the research phase that may involve a paradigm shift in the therapeutic approach of patients with haemophilia, which will allow more personalised treatment, to achieve better joint protection and a better quality of life. Disclosure of Interest None declared

Background In Spain luminal metastatic Breast Cancer accounts for more than 3000 deaths yearly. Ribociclib+letrozole has shown efficacy on prolonging progression free survival (PFS) vs placebo+letrozol in two phase 3 trials. However, data on efficacy and tolerability is lacking for a broader population. We present interim data from CompLEEment-1, an ongoing, open-label, phase 3b trial evaluating ribociclib+letrozole as first-line endocrine therapy in an expanded population of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Methods Patients treated with ≤1 line of prior chemotherapy and no prior endocrine therapy for advanced disease received ribociclib 600 mg/day (3-weeks-on/1week-off) + letrozole (2.5 mg/day; plus monthly goserelin or leuprolide in men and premenopausal women). The primary objective was safety and tolerability. Here we report a sub-analysis of CompLEEment-1 for the Spanish population. Results 526 patients were evaluated over a median follow-up of 10.3 months. Baseline characteristics indicated a diverse population with median age of 55.6 years (range 24-85); 0.8% of patients were male, 34.6% female pre-menopausal and 64.6% female post-menopausal. 71% had visceral metastasis, in 8 cases at the CNS. 55.9% had measurable disease at baseline. The rate of all-grade and grade ≥ 3 treatment-related adverse events (AEs) was 98.5% and 70.0%, respectively. Treatment-related serious AEs occurred in 12.2% of patients. All-grade and grade ≥ 3 AEs leading to ribociclib discontinuation occurred in 13.7% and 8.2% of patients, respectively. Rates of ≥ 3 AEs of special interest (AESI) were 59.5% for neutropenia, 6.8% for increased alanine aminotransferase, 4.8% for increased aspartate aminotransferase, and 0.6% for QTcF prolongation. Patient health-related quality of life was maintained versus baseline. Conclusions Initial results from the Spanish cohort in CompLEEment-1 are consistent with previous data showing efficacy and a manageable safety profile of ribociclib plus letrozole as a first-line treatment option in a diverse group of patients with HR+, HER2– ABC. Acknowledgement: Dr. J. Gavila-Gregori, Dr. M.J. Martinez-Serrano and Dr. M. Perello contributed equally to this study. Clinical trial identification NCT02941926. Legal entity responsible for the study Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure E.M. Ciruelos: Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Speaker and ad.board honoraria: Pfizer. R. Villanueva Vazquez: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche. F. Moreno: Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy: MSD. I. Alvarez: Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. S. Gonzalez-Santiago: Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): AstraZeneca. A. Barnadas: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Genomic Health; Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre. B. Cantos: Research grant / Funding (institution), Study enrollment: Fundacion para la Investigacion del Hospital Puerta de Hierro de Majadahonda; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene; Advisory / Consultancy: AstraZeneca. M. Bellet Ezquerra: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Lilly. M. Martin: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Taiho Oncology; Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Puma. N. Martinez: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.

Gorham-Stout disease is a rare disorder characterized by proliferation of lymphatic and vascular channels within bone resulting in osteolysis. A 53-year-old man with Gorham-Stout disease involving the left maxilla underwent previous treatment including radiation therapy and intralesional chemotherapeutic injections. He later presented with anemia, facial pain, weight loss, and nasal cavity hemorrhage. CT imaging demonstrated a mass centered within the right maxillary sinus with locoregional involvement. PET/CT showed prominent FDG activity involving the mass centered in the right maxillary sinus with low-grade avidity involving the contralateral maxilla in regions of treated Gorham-Stout disease. Biopsy of the mass confirmed radiation-induced sarcoma.

Cellular mechanical properties constitute good markers to characterize tumor cells, to study cell population heterogeneity and to highlight the effect of drug treatments. In this work, we describe the fabrication and validation of an integrated optofluidic chip capable of analyzing cellular deformability on the basis of the pressure gradient needed to push a cell through a narrow constriction. We demonstrate the ability of the chip to discriminate between tumorigenic and metastatic breast cancer cells (MCF7 and MDA-MB231) and between human melanoma cells with different metastatic potential (A375P and A375MC2). Moreover, we show that this chip allows highlighting the effect of drugs interfering with microtubule organization (paclitaxel, combretastatin A-4 and nocodazole) on cancer cells, which leads to changes in the pressure-gradient required to push cells through the constriction. Our single-cell microfluidic device for mechanical evaluation is compact and easy to use, allowing for an extensive use in different laboratory environments.

The development of a 6-wheel remote controlled prototype robot is shown. The robot has two radiation detectors, a 1.5”x1.5” NaI scintillation detector and another Hyper Pure Germanium detector to identify radioactive sources. The robot has a 50Km away in line of sight. The purpose of the robot is to use it as a remotely operated unmanned vehicle for radiological monitoring and search for radioactive sources in case of emergencies. A robot trajectory map with the sampled points of radiological measurements is shown. The map is obtained from geographical-coordinates data of the GPS. A remote visual monitoring station is used for scenario incorporates the radiation data through an On Screen Display module.

This paper presents the analytical controllable workspace boundaries of a crane-type cable-based robot with purely translational motions. The underconstrained cable robot is composed of eight cables which support the weight of a mobile platform, restricting its motions into the vertical plane of a static platform. The analytic equations are developed so that its workspace fulfills the tensionable condition for a given set of minimum and maximum tension limits. The all-tensionable workspace is obtained by analyzing slackness conditions with constant orientation of the mobile platform and by solving the all-positive cable tension redundancy. The minimum two-norm cable tension formulation results in a quadratic equation which admits a minimum value by equaling its derivative to zero.

We present a cost-effective and highly-portable plastic prototype that can be interfaced with a cell phone to implement an optofluidic imaging cytometry platform. It is based on a PMMA microfluidic chip that fits inside an opto-mechanical platform fabricated by a 3D printer. The fluorescence excitation and imaging is performed using the LED and the CMOS from the cell phone increasing the compactness of the system. A custom developed application is used to analyze the images and provide a value of particle concentration.

Introduccion. Existe una creciente necesidad de estudios cientificos e instrumentos que permitan evaluar los efectos en el plano afectivo de algunas terapias no farmacologicas para personas con demencia, como la danza creativa terapeutica. Objetivos. Determinar la validez y fiabilidad del Profile of Mood States (POMS) en personas con demencia y analizar las posibles diferencias en las puntuaciones de los participantes antes y despues de sesiones de danza creativa terapeutica. Pacientes y metodos. El POMS se administro a 36 personas con demencia antes y despues de cuatro sesiones grupales de danza creativa terapeutica. Para comprobar la validez de constructo se administraron dos cuestionarios autoinformados (PANAS y STAXI-2). Resultados. El POMS presento una buena consistencia interna para cada factor y excelente para la escala total. La estabilidad temporal fue media-alta. Los resultados de validez convergente apoyan la validez de constructo. Despues de las sesiones de danza creativa terapeutica, los factores tension, depresion y confusion del POMS se redujeron, mientras que el factor vigor aumento significativamente. No hubo ningun efecto sobre la fatiga y la colera. Conclusiones. Se ha demostrado la validez y fiabilidad del POMS en una poblacion con demencia. La danza creativa terapeutica puede ofrecer beneficios emocionales para personas con demencia.

Two-dimensional transition-metal dichalcogenide materials have recently attracted great attention from the scientific community due to their interesting properties such as the presence of an energy band gap and the support of spin-polarized states. In particular, monolayer molybdenum disulfide has a structure with no inversion symmetry and, thus, presents a large spin-splitting of the top valence bands. This latter fact makes it favorable for studies of optical spin injection, a phenomenon that, under incidence of circularly polarized light, creates spin-polarized electrons in the conduction bands. Here, we perform a theoretical study of the one-photon optical spin and current injection on transition-metal dichalcogenide monolayers of molybdenum disulfide. In particular, we present calculations for spectra of the degree of spin polarization, which are calculated in a full-band structure scheme employing density functional theory; besides the so-called quasiparticle GW approximation is applied for the calculation of the band gap energy correction. Our results show 100% of spin polarization of the electrons for the one monolayer structure at the K valley. The degree of spin polarization also presents a net maximum value at the direct energy band gap at K as the number of monolayers increases.

Road transport is the second largest producer of greenhouse gases within the European Union. This project, Energy Efficient VEhicles for Road Transport (EE-VERT) targets a 10-12% reduction in fuel consumption and CO2 generation for conventional vehicles with only minimal changes. Hybrid Electric Vehicles (HEVs) and Full Electric Vehicles (EVs) offer good CO2 savings but their market penetration is slow, therefore conventional vehicles will play a significant role for the foreseeable future. Despite improvements in modern conventional vehicles, a considerable amount of energy is wasted due to the lack of an overall on-board energy management strategy. Electrification of auxiliary systems and operating them only when needed promises energy and efficiency gains, but there is an additional need for a coordinated approach to the generation, distribution and use of energy. EE-VERT offers a solution to bridge the gap in the market between present conventional vehicles and HEVs/EVs. The central EE-VERT concept is the electrification of auxiliary systems and supplying their energy from energy sources such as recuperated braking energy, waste heat recovery or solar cells, as part of an overall energy management strategy. The conventional car uses a 14V network and the EE-VERT concept retains the majority of this to minimise additional costs. However, to achieve improved efficiency and power, the generator operates at 40V. To connect the elements to the standard electrical system a new architecture has been devised that works with 40V and 14V levels. The main components of the 40V network are a new generator based on the claw pole technology with integrated permanent magnets, a Li-Ion battery system and a DC/DC converter with multiple inputs (MIPEC) for interfacing between the two voltage levels and the additional energy sources such as the solar panel. The available generator power during recuperation is up to 11kW. The efficiency of the new generator is above 80% in the low range of speed while in the high range of speed the efficiency is still above 70%. The MIPEC efficiency is around 94%. The simulation work indicates that average fuel savings of 10% for real life driving cycles and up to 17% when the start and stop functionality is applied to real life urban cycles are possible and that real life urban driving cycles benefit the most from the EE-VERT concept. The final phases of the project work on the Test Bench and with the demonstrator car will confirm the potential fuel saving benefits of the EE-VERT concept.

During the last decade there has been a great development in nanoscience and nanotechnology. The technology of nanostructures synthesis and characterization has grown rapidly and optical spectroscopy has become a very useful characterization technique, since it provides information on the structural, electronic, optical and dynamical properties of materials. Nanostructures have unique physical properties that are different from bulk materials. A wealth of interesting and new phenomena are associated with nanometer-sized structures, such as size-dependent emission or excitation, metallic and semiconductor behavior, etc. Here we present an overview of the linear optical response of one-dimensional silicon nanostructures. In particular, we make a theoretical study of the effects of the size and shape of one-dimensional silicon structures on the absorption spectrum, focusing on the calculation of the linear optical response of clean and hydrogen-adsorbed armchair (6,6) silicon nanotubes. We discuss the changes of the absorption spectrum of silicon nanowires with different diameters and analyze the behavior of the band gap as we go from bulk silicon to one-dimensional silicon nanostructures with nanometer-size diameters.

A fiber laser sensor, which consists of two coupled cavities based on three fiber Bragg gratings (two of them acting as sensing elements) and is interrogated via the longitudinal mode beating frequency, is presented. The two resonant cavities have lengths of 4250 m and 4297 m, respectively. Their beating frequency is of the order of 24 kHz, and its shift as a function of the variation of the period of one (or both) of the sensing gratings, induced by strain or temperature changes, can be measured by a radio-frequency analyzer. The system is suitable for long-distance sensing with high spatial resolution and high sensitivity.