Congenitally deaf children's care trajectories in the context of universal neonatal hearing screening: a qualitative study of the parental experiences

The objective of this study is to examine the early care trajectories of congenitally deaf children from a parental perspective, starting with universal neonatal hearing screenings. The analysis using a three-dimensional care trajectory concept is aimed at developing a basic typology of postscreening care trajectories. Children with severe/profound hearing loss, registered in the Flanders' (Belgium) universal neonatal hearing screening program, born between 1999 and 2001. Thematic content analysis of qualitative data collected retrospectively from participant's parents. Two basic types of care trajectories emerged; based on differences in care-use in the phase of further diagnosis and related parental experiences. Subtypes resulted from events related to cochlear implantation. Five trajectory phases were identified: screening, further diagnosis, care and technology, cochlear implantation, and reduction of care and were characterized by specific parental experiences such as confusion, disbelief, disappointment, and uncertainty. Those experiences relate to care professionals' acts and communication and the child's functional evolution. Early care interventions could benefit from coordinated transition between phases, parent support throughout the care trajectory, and a broad approach to deafness in professionals' communication

Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study

INTRODUCTION: Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. OBJECTIVES: To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. METHODS AND ANALYSIS: This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. ETHICS AND DISSEMINATION: NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal

Experimental study of the sensitivity of a porous silicon ring resonator sensor using continuous in-flow measurements

"© 2017 Optical Society of America. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibited"[EN] A highly sensitive photonic sensor based on a porous silicon ring resonator was developed and experimentally characterized. The photonic sensing structure was fabricated by exploiting a porous silicon double layer, where the top layer of a low porosity was used to form photonic elements by e-beam lithography and the bottom layer of a high porosity was used to confine light in the vertical direction. The sensing performance of the ring resonator sensor based on porous silicon was compared for the different resonances within the analyzed wavelength range both for transverse-electric and transverse-magnetic polarizations. We determined that a sensitivity up to 439 nm/RIU for low refractive index changes can be achieved depending on the optical field distribution given by each resonance/polarization. (C) 2017 Optical Society of America under the terms of the OSA Open Access Publishing AgreementEuropean Commission through the project H2020-644242 SAPHELY; Spanish government through the projects TEC2013-49987-EXP BIOGATE and TEC2015-63838-C3-1-R-OPTONANOSENS; Generalitat Valenciana through the Doctoral Scholarship GRISOLIAP/2014/109.Caroselli, R.; Ponce-Alcántara, S.; Prats-Quílez, F.; Martín-Sánchez, D.; Torrijos-Morán, L.; Griol Barres, A.; Bellieres, LC.... (2017). Experimental study of the sensitivity of a porous silicon ring resonator sensor using continuous in-flow measurements. Optics Express. 25(25):31651-31659. https://doi.org/10.1364/OE.25.031651S31651316592525Estevez, M. C., Alvarez, M., & Lechuga, L. M. (2011). Integrated optical devices for lab-on-a-chip biosensing applications. Laser & Photonics Reviews, 6(4), 463-487. doi:10.1002/lpor.201100025Xu, D. X., Densmore, A., Delâge, A., Waldron, P., McKinnon, R., Janz, S., … Schmid, J. H. (2008). Folded cavity SOI microring sensors for high sensitivity and real time measurement of biomolecular binding. Optics Express, 16(19), 15137. doi:10.1364/oe.16.015137Luchansky, M. S., & Bailey, R. C. (2011). High-Q Optical Sensors for Chemical and Biological Analysis. Analytical Chemistry, 84(2), 793-821. doi:10.1021/ac2029024De Vos, K., Bartolozzi, I., Schacht, E., Bienstman, P., & Baets, R. (2007). Silicon-on-Insulator microring resonator for sensitive and label-free biosensing. Optics Express, 15(12), 7610. doi:10.1364/oe.15.007610Washburn, A. L., Gunn, L. C., & Bailey, R. C. (2009). Label-Free Quantitation of a Cancer Biomarker in Complex Media Using Silicon Photonic Microring Resonators. Analytical Chemistry, 81(22), 9499-9506. doi:10.1021/ac902006pIqbal, M., Gleeson, M. A., Spaugh, B., Tybor, F., Gunn, W. G., Hochberg, M., … Gunn, L. C. (2010). Label-Free Biosensor Arrays Based on Silicon Ring Resonators and High-Speed Optical Scanning Instrumentation. IEEE Journal of Selected Topics in Quantum Electronics, 16(3), 654-661. doi:10.1109/jstqe.2009.2032510Claes, T., Molera, J. G., De Vos, K., Schacht, E., Baets, R., & Bienstman, P. (2009). Label-Free Biosensing With a Slot-Waveguide-Based Ring Resonator in Silicon on Insulator. IEEE Photonics Journal, 1(3), 197-204. doi:10.1109/jphot.2009.2031596Fard, S. T., Donzella, V., Schmidt, S. A., Flueckiger, J., Grist, S. M., Talebi Fard, P., … Chrostowski, L. (2014). Performance of ultra-thin SOI-based resonators for sensing applications. Optics Express, 22(12), 14166. doi:10.1364/oe.22.014166Flueckiger, J., Schmidt, S., Donzella, V., Sherwali, A., Ratner, D. M., Chrostowski, L., & Cheung, K. C. (2016). Sub-wavelength grating for enhanced ring resonator biosensor. Optics Express, 24(14), 15672. doi:10.1364/oe.24.015672YAKOVTSEVA, V., BONDARENKO, V., BALUCANI, M., KAZUCHITS, N., & FERRARI, A. (1999). INTEGRATED OPTICAL WAVEGUIDES BASED ON POROUS SILICON: STATE-OF-THE-ART AND OUTLOOK FOR PROGRESS. Physics, Chemistry and Application of Nanostructures. doi:10.1142/9789812817990_0077Dhanekar, S., & Jain, S. (2013). Porous silicon biosensor: Current status. Biosensors and Bioelectronics, 41, 54-64. doi:10.1016/j.bios.2012.09.045Snow, P. A., Squire, E. K., Russell, P. S. J., & Canham, L. T. (1999). Vapor sensing using the optical properties of porous silicon Bragg mirrors. Journal of Applied Physics, 86(4), 1781-1784. doi:10.1063/1.370968Baratto, C., Faglia, G., Comini, E., Sberveglieri, G., Taroni, A., La Ferrara, V., … Di Francia, G. (2001). A novel porous silicon sensor for detection of sub-ppm NO2 concentrations. Sensors and Actuators B: Chemical, 77(1-2), 62-66. doi:10.1016/s0925-4005(01)00673-6Stefano, L. D., Rotiroti, L., Rea, I., Moretti, L., Francia, G. D., Massera, E., … Rendina, I. (2006). Porous silicon-based optical biochips. Journal of Optics A: Pure and Applied Optics, 8(7), S540-S544. doi:10.1088/1464-4258/8/7/s37Zhang, H., Jia, Z., Lv, X., Zhou, J., Chen, L., Liu, R., & Ma, J. (2013). Porous silicon optical microcavity biosensor on silicon-on-insulator wafer for sensitive DNA detection. Biosensors and Bioelectronics, 44, 89-94. doi:10.1016/j.bios.2013.01.012Kim, K., & Murphy, T. E. (2013). Porous silicon integrated Mach-Zehnder interferometer waveguide for biological and chemical sensing. Optics Express, 21(17), 19488. doi:10.1364/oe.21.019488Rodriguez, G. A., Hu, S., & Weiss, S. M. (2015). Porous silicon ring resonator for compact, high sensitivity biosensing applications. Optics Express, 23(6), 7111. doi:10.1364/oe.23.007111Harraz, F. A. (2014). Porous silicon chemical sensors and biosensors: A review. Sensors and Actuators B: Chemical, 202, 897-912. doi:10.1016/j.snb.2014.06.048Bisi, O., Ossicini, S., & Pavesi, L. (2000). Porous silicon: a quantum sponge structure for silicon based optoelectronics. Surface Science Reports, 38(1-3), 1-126. doi:10.1016/s0167-5729(99)00012-6Bruggeman, D. A. G. (1935). Berechnung verschiedener physikalischer Konstanten von heterogenen Substanzen. I. Dielektrizitätskonstanten und Leitfähigkeiten der Mischkörper aus isotropen Substanzen. Annalen der Physik, 416(7), 636-664. doi:10.1002/andp.19354160705BALILI, R. B. (2012). TRANSFER MATRIX METHOD IN NANOPHOTONICS. International Journal of Modern Physics: Conference Series, 17, 159-168. doi:10.1142/s2010194512008057Pavesi, L. (1997). Porous silicon dielectric multilayers and microcavities. La Rivista del Nuovo Cimento, 20(10), 1-76. doi:10.1007/bf0287737

Integration of hormonal signaling networks and mobile microRNAs is required for vascular patterning in Arabidopsis roots

Peer reviewe

DR9.3 Final report of the JRRM and ASM activities

Deliverable del projecte europeu NEWCOM++This deliverable provides the final report with the summary of the activities carried out in NEWCOM++ WPR9, with a particular focus on those obtained during the last year. They address on the one hand RRM and JRRM strategies in heterogeneous scenarios and, on the other hand, spectrum management and opportunistic spectrum access to achieve an efficient spectrum usage. Main outcomes of the workpackage as well as integration indicators are also summarised.Postprint (published version

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity from a Phase I Study of Simlukafusp Alfa (FAP-IL2v) in Advanced/Metastatic Solid Tumors

Purpose: Simlukafusp alfa [fibroblast activation protein α-targeted IL2 variant (FAP-IL2v)], a tumor-targeted immunocytokine, comprising an IL2 variant moiety with abolished CD25 binding fused to human IgG1, is directed against fibroblast activation protein α. This phase I, open-label, multicenter, dose-escalation, and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/ metastatic solid tumors. Patients and Methods: Participants received FAP-IL2v intravenously once weekly. Dose escalation started at 5 mg; flat dosing (≤25 mg) and intraparticipant uptitration regimens (15/20, 20/25, 20/20/35, and 20/35/35 mg) were evaluated. Primary objectives were dose-limiting toxicities, maximum tolerated dose, recommended expansion dose, and pharmacokinetics. Results: Sixty-one participants were enrolled. Dose-limiting toxicities included fatigue (flat dose 20 mg: n = 1), asthenia (25 mg: n = 1), drug-induced liver injury (uptitration regimen 20/25 mg: n = 1), transaminase increase (20/25 mg: n = 1), and pneumonia (20/35/35 mg: n = 1). The uptitration regimen 15/20 mg was determined as the maximum tolerated dose and was selected as the recommended expansion dose. Increases in peripheral blood absolute immune cell counts were seen for all tested doses [NK cells, 13-fold; CD4+ T cells (including regulatory T cells), 2-fold; CD8+ T cells, 3.5-fold] but without any percentage change in regulatory T cells. Clinical activity was observed from 5 mg [objective response rate, 5.1% (n = 3); disease control rate, 27.1% (n = 16)]. Responses were durable [n = 3, 2.8 (censored), 6.3, and 43.4 months]. Conclusions: FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.</p

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Epidemiology of maxillofacial trauma in the elderly: a European multicenter study

ABSTRACT Introduction: The progressive aging of European population seems to determine a change in the epidemiology, incidence and etiology of maxillofacial fractures with an increase in the frequency of old patients sustaining craniofacial trauma. The objective of the present study was to assess the demographic variables, causes, and patterns of facial fractures in elderly population (with 70 years or more). Materials and Methods: The data from all geriatric patients (70 years or more) with facial fractures between January 1, 2013, and December 31, 2017, were collected. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, etiology, site of facial fractures, synchronous body injuries, Facial Injury Severity Score (FISS). Results: A total of 1334 patients (599 male and 735 female patients) were included in the study. Mean age was 79.3 years, and 66% of patients reported one or more comorbidities. The most frequent cause of injury was fall and zygomatic fractures were the most frequently observed injuries. Falls were associated with a low FISS value (p<.005). Concomitant injuries were observed in 27.3% of patients. Falls were associated with the absence of concomitant injuries. The ninth decade (p <.05) and a high FISS score (p <.005) were associated with concomitant body injuries too. Conclusions: This study confirms the role of falls in the epidemiology of facial trauma in the elderly, but also highlights the frequency of involvement of females, and the high frequency of zygomatic fractures.Peer reviewe

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria.

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves artemisinin-like kill kinetics in vitro with a parasite clearance time of \u3c24 h. A single dose of 30 mg/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance in drug selection studies and a long half-life (T1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials

Gymnemic acids inhibit hyphal growth and virulence in Candida albicans

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine