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The exact incidence of superior mediastinal masses in children is largely unknown. They present as a spectrum of disease ranging from an incidental finding on a Chest X-Ray to being markedly symptomatic with superior vena caval syndrome or obstruction of the upper airways. Lymphomas seem to be the most common causes of superior mediastinal masses in children. We present two cases of confirmed T cell lymphoma in children with superior mediastinal masses. In doing so, we explore a diagnostic approach and visit the complications the physician needs to be aware of when confronted with a child with a superior mediastinal mass.

Thomas HG Bongaerts,1,* Marlieke Ridder,1,2,* Josephina CJ Vermeer-Mens,3 Jeanette J Plukkel,2 Mattijs E Numans,1 Frederike L Büchner1 1Leiden University Medical Center LUMC-Campus the Hague, Department of Public Health and Primary Care, The Hague, the Netherlands; 2Municipal Health Service Rotterdam-Rijnmond, Rotterdam, the Netherlands; 3Erasmus Medical Center, Department of Pathology, Rotterdam, the Netherlands*These authors contributed equally to this workCorrespondence: Thomas HG BongaertsLUMC-Campus the Hague, Department of Public Health and Primary Care, Leiden University Medical Center, Turfmarkt 99, The Hague, 2511 DV, the NetherlandsTel +31 70 800 90 47Email t.h.g.bongaerts@lumc.nlBackground: Many countries organize population-based cervical cancer screening programs (CSP). In the Netherlands, eligible women are invited by mail. Marginalized women living in unstable conditions and homeless women often fail to receive the invitation letter. These women also experience access barriers to regular healthcare. Consequently, despite presumably being at higher risk of developing cervical cancer due to prevalent risk factors, marginalized women are rarely screened for cervical cancer. The aim of the study was to identify the prevalence of (pre)cancerous abnormalities among marginalized women, and subsequently explore invitation approaches to enhance their screening participation.Methods: A cross-sectional intervention study was conducted in Rotterdam, the Netherlands. Between February and May 2019, marginalized women aged 20– 60 years were invited to participate in cervical screening. A participant was considered screen-positive when they tested positive for high-risk human papilloma virus (HR-HPV) and showed cytological abnormalities. Data of the study population were compared with regional data of the Dutch CSP. Various invitation approaches were used to recruit women.Results: Out of 74 included women, 12 participants (16%) were found screen-positive, against 3.4% in women screened by the Dutch CSP. The prevalence ratio for the study population was 4.4 (95% CI 1.9– 8.6) compared with women screened by the Dutch CSP. Using a direct, pro-active approach resulted in participation of 92% of the included women.Conclusion: Marginalized women have an increased risk of (pre)cancerous cervical abnormalities in screening, compared with women screened by the Dutch CSP. A direct pro-active approach was the most effective to stimulate screening participation. Enhancement of screening uptake for this population needs special effort.Keywords: cervical cancer, screening participation, marginalized women, Netherlands

Few data exist on health-related quality of life (QoL) in patients with metastatic pancreatic cancer (mPC) receiving first-line chemotherapy (Awad L ZE, Mesbah M Boston, MA. Applying survival data methodology to analyze quality of life data, in Mesbah M, Cole BF, Ting Lee M-L (eds): Statistical Methods for Quality of Life Studies: Design, Measurements and Analysis. Kluwer Academic Publishers 2002). The QOLIXANE study is a prospective, noninterventional, multicenter substudy of the Platform for Outcome, Quality of Life and Translational Research on Pancreatic Cancer (PARAGON) registry, which evaluated QoL in patients with mPC receiving first-line gemcitabine and nab-paclitaxel chemotherapy in real-life setting. QoL was prospectively measured via EORTC QLQ-C30 questionnaires at baseline and every month thereafter. Therapy and efficacy parameters were prospectively collected. Main objectives were the rate of patients without deterioration of Global Health Status/QoL (GHS/QoL) at 3 and 6 months. Six hundred patients were enrolled in 95 German study sites. Median progression-free survival was 5.9 months (95% confidence interval [CI], 5.2-6.3). Median overall survival (OS) was 8.9 months (95% CI, 7.9-10.2), while median time to deterioration of GHS/QoL was 4.7 months (95% CI, 4.0-5.6). With a baseline GHS/QoL score of 46 (SD, 22.8), baseline QoL of the patients was severely impaired, in most cases due to loss in role functioning and fatigue. In the Kaplan-Meier analysis, 61% and 41% of patients had maintained GHS/QoL after 3 and 6 months, respectively. However, in the QoL response analysis, 35% and 19% of patients had maintained (improved or stable) GHS/QoL after 3 and 6 months, respectively, while 14% and 9% had deteriorated GHS/QoL with the remaining patients being nonevaluable. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a hazard ratio of 0.86 (P < .0001). Patients with mPC have poor QoL at baseline that deteriorates within a median of 4.7 months. Treatment with gemcitabine and nab-paclitaxel is associated with maintained QoL in relevant proportions of patients. However, overall, results remain poor, reflecting the aggressive nature of the disease.

Nintedanib is a triple angiokinase inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-3 and platelet-derived growth factor receptor-a/-b. Thereby, it targets angiogenic escape mechanisms. The trial TyRosine kinase Inhibitor for the treatment of Chemorefractory Colorectal Cancer (TRICC-C) trial evaluates the addition of nintedanib to mFOLFOX6 (fluorouracil, folinic acid and oxaliplatin) in patients with metastatic colorectal cancer (mCRC). TRICC-C is a randomised controlled, double-blinded, phase II trial in mCRC patients that received a first-line non-oxaliplatin containing chemotherapy. Patients received mFOLFOX6 + nintedanib (F + N) (2 × 200 mg p.o./d, d1-d14) or mFOLFOX6 + placebo (F + P), in a 1:1 ratio. Primary endpoint was median progression free survival (mPFS) and secondary overall response rate (ORR), overall survival (OS) and safety. Fifty-three patients (27 F + N; 26 F + P) were randomised between 12/2012 and 5/2016 (scheduled n = 180). The trial was terminated prematurely due to slow accrual. The trial did not reach its primary endpoint but mPFS, median overall survival (mOS) and disease control rate (DCR) were numerically higher in the F + N arm compared to the F + P arm; however, the difference was not significant (mPFS: F + P: 4.6 months vs F + N: 8.1 months; HR 0.65; 95% CI 0.32-1.30; P = .2156; mOS: F + P: 9.9 months vs F + N: 17.1 months; HR 1.03, 95% CI 0.48-2.23; P = .9387; DCR: F + P: 50% vs F + N: 66,7%; P = .2709). Toxicity was moderate and only different for neutropenia (F + P: 11.5%, F + N: 19.2%) and gastrointestinal disorders (F + P: 65.4%, F + N: 84.6%). Final results show safety and a nonsignificant trend towards improved PFS and DCR for the combination of mFOLFOX6 + nintedanib in the second-line therapy of mCRC.

The authors propose a glove with pressure sensitive fingertips and muscle tension detection of the thumb to aid in the physiotherapy of infants, children and adults according to Vojta. The therapy has to be carried out at home by the parents of children with cerebral palsy, or other movement disturbances up to 4 times per day. Often, parents struggle to carry out the practices because of insecurities regarding the therapy’s proper application. The presented glove is tailored towards the specific needs of Vojta therapy, e.g. flexibility and small sensor size, and can help parents gather objective data on their therapy application at home. It has been tested in multiple therapy sessions on adult probands and seems to be a suitable tool to support parents and therapists in training alike. Additionally, the results of the accompanied therapy sessions provide arguments against what the critics have often cited about the painfulness of the therapy.

OBJECTIVES To investigate the intracochlear position of the latest Cochlear Nucleus 532 electrode array compared with the straight Nucleus 522 and the precurved 512 arrays and determine the effect of the electrode-modiolus distance on electrically evoked compound action potential, C-levels, electrically evoked stapedius reflex thresholds (ESRTs), and impedances. METHODS Postoperative high-resolution cone beam computational tomography images of 30 patients with Cochlear Nucleus 532, 522, and 512 implants were evaluated using the Comet (Cochlea Measurement Tool) program to determine the distance between the 22 individual electrode contacts and the medial wall. ESRTs were documented intraoperatively and electrophysiological as well as psychophysical parameters were measured at multiple time points including the first fitting after the initial activation. RESULTS The electrode-modiolus distance in perimodiolar arrays is uniformly small across the array, whereas in a straight electrode carrier it varies significantly along the length of the array. Electrically evoked compound action potential thresholds and C-levels are larger with increased distance to the modiolus. Impedances and stapedius reflex thresholds do not differ significantly between the arrays. Our results show that the electrode position has a significant effect on both electrophysiological and psychophysical parameters, while impedances and ESRTs are not impacted. CONCLUSION Novel tools can be used in the evaluation of high resolution cone beam computational tomography images to determine individual electrode-modiolus distances after cochlear implantation. The results of this study suggest that the correlations between electrode-modiolus distance and electrophysiological and psychophysical parameters are not sufficiently strong to adjust CI-fitting based on imaging data.

BackgroundAn efficient diagnostic pathway and early stage diagnosis for cancer patients is widely pursued. This study aims to chart the duration of the diagnostic pathway for patients with symptomatic oesophageal and gastric cancer, to identify factors associated with long duration and to assess the association of duration with tumour stage at diagnosis.MethodsThis was a retrospective cohort study, using electronic health records of six routine primary care databases covering about 640,000 patients, partly linked to the Netherlands Cancer Registry. Symptomatic patients with oesophageal and gastric cancer (2010-2015) that presented in primary care were included. Duration of four diagnostic intervals was determined: patient interval; first symptoms to primary care consultation, primary care interval; consultation to referral, secondary care interval; referral to diagnosis, and the diagnostic interval; consultation to diagnosis. Characteristics associated with 'long duration' (>= P75 duration) were assessed using log-binomial regression. Median durations were stratified for tumour stages.ResultsAmong 312 symptomatic patients with upper gastrointestinal cancer, median durations were: patient interval: 29 days (interquartile interval 15-73), primary care interval: 12 days (interquartile interval 1-43), secondary care interval: 13 days (interquartile interval 6-29) and diagnostic interval: 31 days (11-74). Patient interval duration was comparable for patients with and without alarm symptoms. Absence of cancer-specific alarm symptoms was associated with 'long duration' of primary care interval and secondary care interval: relative risk 5.0 (95% confidence interval 2.7-9.1) and 2.1 (95% confidence interval 1.3-3.7), respectively. Median diagnostic interval duration for local stage disease was 51 days (interquartile interval 13-135) versus 27 days (interquartile interval 11-71) for advanced stage (p = 0.07).ConclusionIn the diagnostic pathway of upper gastrointestinal cancers, the longest interval is the patient interval. Reducing time to diagnosis may be achieved by improving patients' awareness of alarm symptoms and by diagnostic strategies which better identify cancer patients despite low suspicion.

We show that machine learning methods, in particular, extreme trees and neural networks (NNs), provide strong statistical evidence in favor of bond return predictability. NN forecasts based on macroeconomic and yield information translate into economic gains that are larger than those obtained using yields alone. Interestingly, the nature of unspanned factors changes along the yield curve: stock- and labor-market-related variables are more relevant for short-term maturities, whereas output and income variables matter more for longer maturities. Finally, NN forecasts correlate with proxies for time-varying risk aversion and uncertainty, lending support to models featuring both channels.

The metal–organic interface between polycrystalline gold and hexafluorotetracyanonaphthoquinodimethane (F6TCNNQ) was investigated by photoelectron spectroscopy with the focus on the charge transfer characteristics from the metal to the molecule. The valence levels, as well as the core levels of the heterojunction, indicate a full electron transfer and a change in the chemical environment. The changes are observed in the first F6TCNNQ layers, whereas for further film growth, only neutral F6TCNNQ molecules could be detected. New occupied states below the Fermi level were observed in the valence levels, indicating a lowest unoccupied molecular orbital (LUMO) occupation due to the charge transfer. A fitting of the spectra reveals the presence of a neutral and a charged F6TCNNQ molecules, but no further species were present.

Purpose Hearing performance data was collected from a large heterogeneous group of subjects implanted with the Cochlear™ Nucleus® CI532 with Slim Modiolar Electrode, for the purposes of postmarket clinical follow-up. Data was analysed for factors which may predict postoperative speech recognition scores. Methods Data was collected retrospectively from five German clinics for 159 subjects from March 2017 to August 2018. Hearing thresholds and recognition scores for monosyllabic words in quiet and sentences in noise were measured preoperatively and at 3 and 6 months postoperatively. Results There was a mean gain of 44% points (95% CI 39–49%) at 6 months in monosyllable scores in quiet for implanted ears. Preoperative hearing thresholds in implant ears increased systematically with decreasing age; however, younger subjects had better baseline monosyllable scores with hearing aids compared with older subjects. Baseline performance alone explained 14% of the variation in postoperative scores. Residual hearing was preserved on average to within 22 dB at 250 Hz and 30 dB at 500 Hz of preoperative levels. Conclusions In a large and varied cohort of routinely treated hearing-impaired adults, speech recognition with the CI532 for German monosyllabic words in quiet at 6 months was equivalent to performance reported at one year or more in other published studies. Although younger subjects had poorer preoperative pure-tone thresholds, they had better preoperative word recognition scores compared with older subjects, and also had higher post implant scores. Further research is required to identify if this phenomenon is just applicable to German health system assessment and referral practices.

To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa. Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both. Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p

Today's use of large-scale industrial robots is enabling extraordinary achievement on the assembly line, but these robots remain isolated from the humans on the factory floor because they are very powerful, and thus dangerous to be around. In contrast, the soft robotics research community has proposed soft robots that are safe for human environments. The current state of the art enables the creation of small-scale soft robotic devices. In this article we address the gap between small-scale soft robots and the need for human-sized safe robots by introducing a new soft robotic module and multiple human-scale robot configurations based on this module. We tackle large-scale soft robots by presenting a modular and reconfigurable soft robotic platform that can be used to build fully functional and untethered meter-scale soft robots. These findings indicate that a new wave of human-scale soft robots can be an alternative to classic rigid-bodied robots in tasks and environments where humans and machines can work side by side with capabilities that include, but are not limited to, autonomous legged locomotion and grasping.

Context Contemporary resource management paradigms within the developed world build on an understanding of human agency as ontologically distinct from the mode of existence of plants and animals. Because of this perspective, which gives priority to human agency, policies typically take their point of departure with human societies and associated ecosystems deemed of particular value. Objectives As an alternative to this worldview, social theorists have introduced what is known as “flat ontology”, where all beings are bestowed equal rights to negotiate their existence. To explore the implications of introducing such an understanding into landscape management, a participatory planning process for water allocation was developed and tested in a case study in the Eerste River Catchment in South Africa. Methods The planning process was mediated using the approach “politics of nature” (PoN), which aims to operationalize flat ontology to renegotiate water allocation based on the needs of all beings instead of the desire of a subset of humans. PoN allowed participants to playfully co-develop a common ontology and value-set. Data documenting these processes were collected digitally and analysed. Results Results indicate that the approach engendered a rethinking of key relationships between human agency and ecosystem functionality, illustrating a potential for PoN-approaches to be deployed for governance of complex landscapes. Conclusions On the basis of experiments using PoN-methodology in the context of watershed management, it is discussed how the introduction of a flat ontology in landscape research, could inspire new ways of designing and intervening with collaborative resource management processes. Supplementary Information The online version contains supplementary material available at 10.1007/s10980-021-01374-9.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a huge challenge for contemporary healthcare systems. Apart from widely reported acute respiratory distress syndrome (ARDS), the virus affects many other systems inducing a vast number of symptoms such as gastrointestinal, neurological, dermatological, cardiovascular, and many more. Currently it has also been hypothesized that the virus might affect female and male reproductive systems; SARS-CoV-2 infection could also have a role in potential disturbances to human fertility. In this article, we aimed to review the latest literature regarding the potential effects of SARS-CoV-2 infection on female and male reproductive systems as well as fertility, in general.

ObjectivesFocusing attention on one speaker in a situation with multiple background speakers or noise is referred to as auditory selective attention. Decoding selective attention is an interesting line of research with respect to future brain-guided hearing aids or cochlear implants (CIs) that are designed to adaptively adjust sound processing through cortical feedback loops. This study investigates the feasibility of using the electrodes and backward telemetry of a CI to record electroencephalography (EEG).ApproachThe study population included 6 normal-hearing (NH) listeners and 5 CI users with contralateral acoustic hearing. Cortical auditory evoked potentials (CAEP) and selective attention were recorded using a state-of-the-art high-density scalp EEG and, in the case of CI users, also using two CI electrodes as sensors in combination with the backward telemetry system of these devices (iEEG).Main resultsThe peak amplitudes of the CAEPs recorded with iEEG were lower and the latencies were higher than those recorded with scalp EEG. In the selective attention paradigm with multi-channel scalp EEG the mean decoding accuracy across subjects was 92.0 and 92.5% for NH listeners and CI users, respectively. With single-channel scalp EEG the accuracy decreased to 65.6 and to 75.8% for NH listeners and CI users, respectively, and was above chance level in 9 out of 11 subjects. With the single-channel iEEG, the accuracy for CI users decreased to 70% and was above chance level in 3 out of 5 subjects.SignificanceThis study shows that single-channel EEG is suitable for auditory selective attention decoding, even though it reduces the decoding quality compared to a multi-channel approach. CI-based iEEG can be used for the purpose of recording CAEPs and decoding selective attention. However, the study also points out the need for further technical development for the CI backward telemetry regarding long-term recordings and the optimal sensor positions.

Aims: Image-defined risk factors (IDRFs) in neuroblastoma predict surgical complications and management outcomes. As there is a lack of data regarding the association of IDRFs with clinical and pathological factors, this study evaluated the prognostic value of IDRFs to predict neuroblastoma survival outcomes. Materials and methods: This was a retrospective study including 345 patients and reviewed diagnostic imaging for 20 IDRFs, pleural effusions and ascites. The IDRFs were grouped into five `primary IDRFs' cohorts with vascular encasement, involvement of multiple body compartments, organ infiltration, airway obstruction and intraspinal extension. The association between clinical, histopathological and biological characteristics of neuroblastoma and management was evaluated. Results: More patients without IDRFs had operations compared with patients with IDRFs, with a trend towards significance (64.4% versus 35.6%, P = 0.082). Patients with multiple compartment tumour involvement (P = 0.003) and organ infiltration (P < 0.001) had a higher risk of surgical complications. The 5-year overall survival of the group with more than one IDRF was 0.0% and those with pleural effusions or ascites 6.7%, associated with the worst outcome (P = 0.005). The total number of IDRFs was not predictive of the metastatic remission rate (P = 0.585) or overall survival (P = 0.142), with no conclusive association found between IDRF groups and clinical or biological markers. Conclusions: Patients with more than one IDRF had the shortest survival time, whereas those with pleural effusions and ascites at diagnosis had a poor outcome. Standardised reporting of IDRFs is crucial for predicting prognosis. (C) 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background and Objectives:Early identification of child mental health problems (MHPs) is important to provide adequate, timely treatment. Dutch preventive youth healthcare monitors all aspects of a child's healthy development. We explored the usefulness of their electronic health records (EHRs) in scientific research and aimed to develop prediction models for child MHPs.Methods:Population-based cohort study with anonymously extracted electronic healthcare data from preventive youth healthcare centers in the Leiden area, the Netherlands, from the period 2005–2015. Data was analyzed with respect to its continuity, percentage of cases and completeness. Logistic regression analyses were conducted to develop prediction models for the risk of a first recorded concern for MHPs in the next scheduled visit at age 3/4, 5/6, 10/11, and 13/14 years.Results:We included 26,492 children. The continuity of the data was low and the number of concerns for MHPs varied greatly. A large number of determinants had missing data for over 80% of the children. The discriminatory performance of the prediction models were poor.Conclusions:This is the first study exploring the usefulness of EHRs from Dutch preventive youth healthcare in research, especially in predicting child MHPs. We found the usefulness of the data to be limited and the performance of the developed prediction models was poor. When data quality can be improved, e.g., by facilitating accurate recording, or by data enrichment from other available sources, the analysis of EHRs might be helpful for better identification of child MHPs.

Against the background of increasing numbers of indications for Cochlea implants (CIs), there is an increasing need for a CI outcome prediction tool to assist the process of deciding on the best possible treatment solution for each individual patient prior to intervention. The hearing outcome depends on several features in cochlear structure, the influence of which is not entirely known as yet. In preparation for surgical planning a preoperative CT scan is recorded. The overall goal is the feature extraction and prediction of the hearing outcome only based on this conventional CT data. Therefore, the aim of our research work for this paper is the preprocessing of the conventional CT data and a following segmentation of the human cochlea. The great challenge is the very small size of the cochlea in combination with a fairly bad resolution. For a better distinction between cochlea and surrounding tissue, the data has to be rotated in a way the typical cochlea shape is observable. Afterwards, a segmentation can be performed which enables a feature detection. We can show the effectiveness of our method compared to results in literature which were based on CT data with a much higher resolution. A further study with a much larger amount of data is planned.

This paper addresses the carbon co-doping of Ce-doped garnets, an efficient scintillation material and white light phosphor. The composition and the optical and scintillation properties of carbon-c...

Background Disease clustering is a growing public health concern and is increasingly linked to adverse socioeconomic conditions. Few population-based studies have focussed on interaction between non-communicable diseases. In this cross-sectional study, we examine clustering of, and synergistic interactions between, frequently occurring non-communicable diseases in Katwijk, a former fishing village in the Netherlands. Additionally, our study identifies contextual variables associated with these clusters of non-communicable diseases. Methods In a survey among adults (>19 years) living in the former fishing village Katwijk, Netherlands, were asked about non-communicable diseases, psychological distress, self-rated health scores and contextual factors, eg, socio-demographic, psychosocial and health behavior characteristics. Interaction was measured on the additive and the multiplicative scale. We used generalized ordered logistic regression analysis to examine associations with contextual variables. Results Three disease clusters were found to be most prevalent among the study participants (n=1408). Each cluster involved a combination of frequently occurring conditions in this population: psychological distress (n=261, 19%), cardiometabolic diseases (n=449, 32%) and musculoskeletal pain (n=462, 33%). These three diseases interact synergistically on the additive scale to increase the odds of reporting a low self-rated health. None of the disease clusters showed a statistically significant positive interaction on a multiplicative scale. Multiple contextual factors were associated with these disease clusters, including gender, loneliness, experiencing financial stress, and a BMI≥30. Conclusion Our findings imply that psychological distress, cardiometabolic diseases and musculoskeletal pain synergistically interact, leading to a much lower self-rated health than expected. Several contextual factors are related to this interaction emphasizing the importance of a multicomponent, ecological approach.

The measurement of the electrically evoked compound action potential (ECAP) in cochlear implant (CI) patients is widely used to provide evidence of a functioning electrode-nerve interface, to confirm proper location of the electrode array and to program the sound processor. In patients with an auditory brainstem implant (ABI), a likewise versatile measurement would be desirable. The ECAP measurement paradigm “Alternating Polarity” was utilized to record responses via the implanted ABI electrode array placed on the cochlear nucleus. Emphasizing on the different location of stimulation and recording, these responses are called local evoked potentials (LEP). LEP measurements were conducted during the clinical routine in 16 ABI patients (12 children and 4 adults), corresponding to 191 electrode contacts. A retrospective analysis of these data revealed, that LEP responses were observed in 64.9% of all measured electrode contacts. LEP responses predicted auditory perception with a sensitivity of 90.5%. False-positive rate was 33.7%. Objective LEP thresholds were highly significantly (p < 0.001) correlated both to behavioral thresholds (Pearson’s r = 0.697) and behavioral most comfortable levels (r = 0.840). Therefore, LEP measurements have the potential to support fitting in ABI patients.

Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = −1.96 per increase of one point in the ALSFRS-R score, p < 0.001). “Limb-onset” ALS (lALS) was associated with a better QoL than “bulbar-onset” ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = −7.60, p = 0.001), being tracheostomized (β = −14.80, p = 0.004) and using non-invasive ventilation (β = −5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care., publishedVersion

Hybrid metallic nanoparticles encapsulated in oxide shells are currently intensely studied for plasmonic applications in sensing, medicine, catalysis, and photovoltaics. Here, we introduce a method for the synthesis of Au@Ag@SiO$_2$ cubes with a uniform silica shell of variable and adjustable thickness in the nanometer range; and we demonstrate their excellent, highly reproducible, and tunable optical response. Varying the silica shell thickness, we could tune the excitation energies of the single nanoparticle plasmon modes in a broad spectral range between 2.55 and 3.25\,eV. Most importantly, we reveal a strong coherent coupling of the surface plasmons at the silver-silica interface with the whispering gallery resonance at the silica-vacuum interface leading to a significant field enhancement at the encapsulated nanoparticle surface in the range of 100\,\% at shell thicknesses $t\,$$\simeq\,$20\,nm. Consequently, the synthesis method and the field enhancement open pathways to a widespread use of silver nanoparticles in plasmonic applications including photonic crystals and may be transferred to other non-precious metals.

Purpose The aim of the World Health Organization-International Paediatric Oncology Society is to improve childhood cancer survival in low- and middle-income countries to 60% by 2030. This can be achieved using standardised evidence-based national treatment protocols for common childhood cancers. The aim of the study was to describe the development and implementation of the SACCSG NB-2017 neuroblastoma (NB) treatment protocol as part of the treatment harmonisation process of the South African Children’s Cancer Study Group. Methods The Consolidated Framework for Implementation Research was used to identify factors that could influence the implementation of the national NB protocol as a health care intervention. The evaluation was done according to five interactive domains for implementation: intervention characteristics, inner setting, outer setting, individual or team characteristics and the implementation process. Results The protocol was developed over 26 months by 26 physicians involved in childhood cancer management. The process included an organisational phase, a resource identification phase, a development phase and a research ethics approval phase. Challenges included nationalised inertia, variable research ethical approval procedures with delays and uncoordinated clinical trial implementation. Conclusion The implementation of the national NB protocol demonstrated the complexity of the implementation of a national childhood cancer treatment protocol. However, standardised paediatric cancer treatment protocols based on local expertise and resources in limited settings are feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-021-01424-2.

22 pages, 5 figures, 1 table, supplementary information https://doi.org/10.1038/s41558-021-01173-9.-- Data availabilityAll standardized forcing variables from the ESMs are available at https://doi.org/10.48364/ISIMIP.575744.1; all outputs from the MEMs are available via ISIMIP (https://www.isimip.org/gettingstarted/data-access/).-- Code availabilityAll code used to analyse simulations is available at https://github.com/Fish-MIP/CMIP5vsCMIP6, Projections of climate change impacts on marine ecosystems have revealed long-term declines in global marine animal biomass and unevenly distributed impacts on fisheries. Here we apply an enhanced suite of global marine ecosystem models from the Fisheries and Marine Ecosystem Model Intercomparison Project (Fish-MIP), forced by new-generation Earth system model outputs from Phase 6 of the Coupled Model Intercomparison Project (CMIP6), to provide insights into how projected climate change will affect future ocean ecosystems. Compared with the previous generation CMIP5-forced Fish-MIP ensemble, the new ensemble ecosystem simulations show a greater decline in mean global ocean animal biomass under both strong-mitigation and high-emissions scenarios due to elevated warming, despite greater uncertainty in net primary production in the high-emissions scenario. Regional shifts in the direction of biomass changes highlight the continued and urgent need to reduce uncertainty in the projected responses of marine ecosystems to climate change to help support adaptation planning, This work was supported by the Jarislowsky Foundation (D.P.T.), the Natural Sciences and Engineering Research Council of Canada Discovery Grant programme (D.P.T., H.K.L., T.D.E., W.W.L.C., J.P.-A. and V.C.); Australian Research Council (ARC) Discovery Projects DP170104240 (J.L.B. and C.N.), DP190102293 (J.L.B., C.N., A.J.R., J.D.E. and D.P.T.) and DP150102656 (J.D.E.); the European Union’s Horizon 2020 research and innovation programme under grant agreements 817578 (TRIATLAS) (M.C., J.S., L.S., O.M., L.B., Y.-J.S., N.B. and J.R.), 869300 (FutureMARES) (J.A.F.-S.,Y.-J.S. and M.C.) and 862428 (MISSION ATLANTIC (J.A.F.-S, Y.-J.S. and M.C.); the Spanish National Project ProOceans (PID2020-118097RB-I00) (M.C. and J.S.); the Open Philanthropy Project (C.S.H.); the United Kingdom Research and Innovation (UKRI) Global Challenges Research Fund (GCRF) One Ocean Hub (NE/S008950/1) (K.O.-C. and L.S.); the Simons Foundation (nos. 54993, 645921) (G.L.B.); the Belmont Forum and BiodivERsA under the BiodivScen ERA-Net COFUND programme (SOMBEE project, ANR-18-EBI4-0003-01) (Y.-J.S. and N.B.); the MEOPAR Postdoctoral Fellowship Award 2020–2021 and the Ocean Frontier Institute (Module G) (A.B.-B.); the French ANR project CIGOEF (grant ANR-17-CE32-0008-01) (O.M., L.B. and J.R.); the California Ocean Protection Council Grant C0100400, the Alfred P. Sloan Foundation and the Extreme Science and Engineering Discovery Environment (XSEDE) allocation TG-OCE170017 (D.B. and J.G.); the National Oceanographic and Atmospheric Association (NA20OAR4310441, NA20OAR4310442) (C.M.P.). M.C. acknowledges the Severo Ochoa Centre of Excellence accreditation (CEX2019-000928-S) to the Institute of Marine Science (ICM-CSIC)

CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2, iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%, treatment difference: 30%, 95%CI &minus, 18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31, 95%CI 0.11, 0.86, p = 0.009, FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.

This study proposes a framework for mining temporal patterns from Electronic Medical Records. A new scoring scheme based on the Wilson interval is provided to obtain frequent and predictive patterns, as well as to accelerate the mining process by reducing the number of patterns mined. This is combined with a case study using data from general practices in the Netherlands to identify children at risk of suffering from mental disorders. To develop an accurate model, feature engineering methods such as one hot encoding and frequency transformation are proposed, and the pattern selection is tailored to this type of clinical data. Six machine learning models are trained on five age groups, with XGBoost achieving the highest AUC values (0.75–0.79) with sensitivity and specificity above 0.7 and 0.6 respectively. An improvement is demonstrated by the models learning from patterns in addition to non-temporal features.

Context.The Extreme Ultraviolet Imager (EUI) is part of the remote sensing instrument package of the ESA/NASA Solar Orbiter mission that will explore the inner heliosphere and observe the Sun from vantage points close to the Sun and out of the ecliptic. Solar Orbiter will advance the “connection science” between solar activity and the heliosphere.Aims.With EUI we aim to improve our understanding of the structure and dynamics of the solar atmosphere, globally as well as at high resolution, and from high solar latitude perspectives.Methods.The EUI consists of three telescopes, the Full Sun Imager and two High Resolution Imagers, which are optimised to image in Lyman-αand EUV (17.4 nm, 30.4 nm) to provide a coverage from chromosphere up to corona. The EUI is designed to cope with the strong constraints imposed by the Solar Orbiter mission characteristics. Limited telemetry availability is compensated by state-of-the-art image compression, onboard image processing, and event selection. The imposed power limitations and potentially harsh radiation environment necessitate the use of novel CMOS sensors. As the unobstructed field of view of the telescopes needs to protrude through the spacecraft’s heat shield, the apertures have been kept as small as possible, without compromising optical performance. This led to a systematic effort to optimise the throughput of every optical element and the reduction of noise levels in the sensor.Results.In this paper we review the design of the two elements of the EUI instrument: the Optical Bench System and the Common Electronic Box. Particular attention is also given to the onboard software, the intended operations, the ground software, and the foreseen data products.Conclusions.The EUI will bring unique science opportunities thanks to its specific design, its viewpoint, and to the planned synergies with the other Solar Orbiter instruments. In particular, we highlight science opportunities brought by the out-of-ecliptic vantage point of the solar poles, the high-resolution imaging of the high chromosphere and corona, and the connection to the outer corona as observed by coronagraphs.

All authors: Zouganelis, I.; De Groof, A.; Walsh, A. P.; Williams, D. R.; Müller, D.; St Cyr, O. C.; Auchère, F.; Berghmans, D.; Fludra, A.; Horbury, T. S.; Howard, R. A.; Krucker, S.; Maksimovic, M.; Owen, C. J.; Rodríguez-Pacheco, J.; Romoli, M.; Solanki, S. K.; Watson, C.; Sanchez, L.; Lefort, J.; Osuna, P.; Gilbert, H. R.; Nieves-Chinchilla, T.; Abbo, L.; Alexandrova, O.; Anastasiadis, A.; Andretta, V.; Antonucci, E.; Appourchaux, T.; Aran, A.; Arge, C. N.; Aulanier, G.; Baker, D.; Bale, S. D.; Battaglia, M.; Bellot Rubio, L.; Bemporad, A.; Berthomier, M.; Bocchialini, K.; Bonnin, X.; Brun, A. S.; Bruno, R.; Buchlin, E.; Büchner, J.; Bucik, R.; Carcaboso, F.; Carr, R.; Carrasco-Blázquez, I.; Cecconi, B.; Cernuda Cangas, I.; Chen, C. H. K.; Chitta, L. P.; Chust, T.; Dalmasse, K.; D'Amicis, R.; Da Deppo, V.; De Marco, R.; Dolei, S.; Dolla, L.; Dudok de Wit, T.; van Driel-Gesztelyi, L.; Eastwood, J. P.; Espinosa Lara, F.; Etesi, L.; Fedorov, A.; Félix-Redondo, F.; Fineschi, S.; Fleck, B.; Fontaine, D.; Fox, N. J.; Gandorfer, A.; Génot, V.; Georgoulis, M. K.; Gissot, S.; Giunta, A.; Gizon, L.; Gómez-Herrero, R.; Gontikakis, C.; Graham, G.; Green, L.; Grundy, T.; Haberreiter, M.; Harra, L. K.; Hassler, D. M.; Hirzberger, J.; Ho, G. C.; Hurford, G.; Innes, D.; Issautier, K.; James, A. W.; Janitzek, N.; Janvier, M.; Jeffrey, N.; Jenkins, J.; Khotyaintsev, Y.; Klein, K. -L.; Kontar, E. P.; Kontogiannis, I.; Krafft, C.; Krasnoselskikh, V.; Kretzschmar, M.; Labrosse, N.; Lagg, A.; Landini, F.; Lavraud, B.; Leon, I.; Lepri, S. T.; Lewis, G. R.; Liewer, P.; Linker, J.; Livi, S.; Long, D. M.; Louarn, P.; Malandraki, O.; Maloney, S.; Martinez-Pillet, V.; Martinovic, M.; Masson, A.; Matthews, S.; Matteini, L.; Meyer-Vernet, N.; Moraitis, K.; Morton, R. J.; Musset, S.; Nicolaou, G.; Nindos, A.; O'Brien, H.; Orozco Suarez, D.; Owens, M.; Pancrazzi, M.; Papaioannou, A.; Parenti, S.; Pariat, E.; Patsourakos, S.; Perrone, D.; Peter, H.; Pinto, R. F.; Plainaki, C.; Plettemeier, D.; Plunkett, S. P.; Raines, J. M.; Raouafi, N.; Reid, H.; Retino, A.; Rezeau, L.; Rochus, P.; Rodriguez, L.; Rodriguez-Garcia, L.; Roth, M.; Rouillard, A. P.; Sahraoui, F.; Sasso, C.; Schou, J.; Schühle, U.; Sorriso-Valvo, L.; Soucek, J.; Spadaro, D.; Stangalini, M.; Stansby, D.; Steller, M.; Strugarek, A.; Štverák, Š.; Susino, R.; Telloni, D.; Terasa, C.; Teriaca, L.; Toledo-Redondo, S.; del Toro Iniesta, J. C.; Tsiropoula, G.; Tsounis, A.; Tziotziou, K.; Valentini, F.; Vaivads, A.; Vecchio, A.; Velli, M.; Verbeeck, C.; Verdini, A.; Verscharen, D.; Vilmer, N.; Vourlidas, A.; Wicks, R.; Wimmer-Schweingruber, R. F.; Wiegelmann, T.; Young, P. R.; Zhukov, A. N., Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission's science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit's science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter's SAP through a series of examples and the strategy being followed. © 2020 ESO., Solar Orbiter is a space mission of international collaboration between ESA and NASA with contributions from national agencies of ESA member states. The spacecraft has been developed by Airbus and is being operated by ESA from the European Space Operations Centre (ESOC) in Darmstadt, Germany. Science operations are carried out at ESA's European Space Astronomy Centre (ESAC) in Villafranca del Castillo, Spain. SWA is an international collaboration which has been funded by the UKSA, CNES, ASI, NASA and the Czech contribution to the ESA PRODEX programme. UAH authors want to thanks the Spanish MINECO-FPI-2016 predoctoral grant with FSE, and its project FEDER/MCIU-AEEI/Proyecto ESP2017-88436-R. The Spanish contribution to SO/PHI has been funded by the Spanish Ministry of Science and Innovation through several projects, the last one being RTI2018-096886-B-C5, and by "Centro de Excelencia Severo Ochoa" programme under grant SEV-2017-0709. RAH, RCC, DMM, SPP, and AV acknowledge the support of the NASA Heliophysics Division, Solar Orbiter Collaboration Office under IAT NNG09EK11I. JEP acknowledges grant UKRI/STFC ST/N000692/1. All French involvements are supported by CNES and CNRS. DV is supported by the STFC Ernest Rutherford Fellowship ST/P003826/1 and STFC Consolidated Grant ST/S000240/1. The authors thank the referee for her constructive comments and suggestions, which led to the substantial improvement of this paper.

Background Previous studies in the field of cochlear implantation have proven that the use of electro-acoustic stimulation systems in patients with low frequency residual hearing results in improved speech perception scores compared to electric only stimulation. Unfortunately, many patients cannot use these systems because of inflammatory responses to the external ear piece of the system. In these cases, the substitution of low frequency acoustic stimulation through an external ear piece by mechanical stimulation with a middle ear implant could be a way to take advantage of the remaining residual hearing. Case We report on a patient who was bilaterally implanted with a MED-EL Vibrant Soundbridge. After 12 years, her hearing loss had progressed such that she was acoustically indicated for electro-acoustic stimulation. Since she could not wear an external ear piece due to medical reasons, she was then implanted with a cochlear implant in addition to her middle ear implant on the right-hand side, hence benefitting from electro-mechanical stimulation in the right ear. For the follow-up period of 12 month her hearing loss was found stable, and speech perception results were satisfying. Conclusion The ipsilateral use of a Vibrant Soundbridge in addition to a cochlear implant was found to be a feasible and save option for providing electro-mechanical auditory stimulation. Speech performance results comparable to electro-acoustic stimulation patients can be expected for patients with substantial low frequency residual hearing.

When the impedance of an electrode contact is highly increased in a cochlear implant, a failure of the appropriate electrode seems obvious. We present a case where impedances of some electrodes were at the lower edge of the normal range and not regarded as suspicious neither by the clinical fitting software nor by in-vivo tests conducted by the implant manufacturer. However, speech comprehension was substantially degraded and sound perception distorted. Also, on the affected electrodes, loudness perception was compromised and responses of the electrically evoked compound action potential were no longer measureable. After re-implantation, the subjective sound percept was clear again and speech comprehension scored much better than before. Later, inspection of the explant revealed shorts on the device and the implant was classified as device failure. Our case shows the importance of collecting longitudinal data of cochlear implant patients, i.e. device related technical measurements and hearing performance data, and the consideration of all these data in cases of patient complaints or suspected implant failures. Laryngoscope, 131:E1275-E1278, 2021.

OBJECTIVES Preservation of residual hearing is one of the main goals in present cochlear implantation surgery. Especially for this purpose, smaller and softer electrode carriers were developed that are to be inserted through the round window membrane to minimize trauma. By using these electrodes and insertion technique, residual hearing can be preserved in a large number of patients. Unfortunately, some of these patients with initially preserved residual hearing after cochlear implantation lose it later on. The reason for this is unknown but it is speculated about a correlation with an increase in impedance, since increased impedance values are linked to intracochlear inflammation and tissue reaction. Our hypothesis for this study design was that an increase in impedance predicts changes in residual hearing under clinical conditions. DESIGN Data of all adult patients (N = 122) receiving a Hybrid-L24 cochlear implant at our center between 2005 and early 2015 were retrospectively evaluated. Impedance values in Common Ground mode as measured during clinical routine and referring audiological test data (audiometric thresholds under headphones) were collected. Changes between consecutive measurements were calculated for impedance values and hearing thresholds for each patient. Correlations between changes in impedances and acoustic hearing thresholds were calculated. Average values were compared as well as patients with largest impedance changes within the observation period were evaluated separately. RESULTS Group mean values of impedances were between 5 and 7 kΩ and stable over time with higher values on basal electrode contacts compared with apical contacts. Average hearing thresholds at the time of initial fitting were between 40 to 50 dB (250 Hz) and 90 dB (1 kHz) with a loss of about 10 dB compared with preoperative values. Correlation between impedance changes and threshold changes was found, but too inconsistently to imply a true relationship. When evaluating the 20 patients with the largest impedance changes during the observation period (all >1 kΩ from one appointment to the next one), some patients were found where hearing loss is timely connected and highly correlated with an unusual impedance change. But large impedance changes were also observed without affecting hearing thresholds and hearing loss was found without impedance change. CONCLUSIONS Changes in impedance as measured during clinical routine cannot be taken as an indicator for a late acoustic hearing loss.

Cochlear implantation constitutes a successful therapy of inner ear deafness, with the majority of patients showing good outcomes. There is, however, still some unexplained variability in outcomes with a number of cochlear-implant (CI) users, showing major limitations in speech comprehension. The current study used a multimodal diagnostic approach combining single-photon emission computed tomography (SPECT) and electroencephalography (EEG) to examine the mechanisms underlying speech processing in postlingually deafened CI users (N = 21). In one session, the participants performed a speech discrimination task, during which a 96-channel EEG was recorded and the perfusions marker 99mTc-HMPAO was injected intravenously. The SPECT scan was acquired 1.5 h after injection to measure the cortical activity during the speech task. The second session included a SPECT scan after injection without stimulation at rest. Analysis of EEG and SPECT data showed N400 and P600 event-related potentials (ERPs) particularly evoked by semantic violations in the sentences, and enhanced perfusion in a temporo-frontal network during task compared to rest, involving the auditory cortex bilaterally and Broca’s area. Moreover, higher performance in testing for word recognition and verbal intelligence strongly correlated to the activation in this network during the speech task. However, comparing CI users with lower and higher speech intelligibility [median split with cutoff + 7.6 dB signal-to-noise ratio (SNR) in the Göttinger sentence test] revealed for CI users with higher performance additional activations of parietal and occipital regions and for those with lower performance stronger activation of superior frontal areas. Furthermore, SPECT activity was tightly coupled with EEG and cognitive abilities, as indicated by correlations between (1) cortical activation and the amplitudes in EEG, N400 (temporal and occipital areas)/P600 (parietal and occipital areas) and (2) between cortical activation in left-sided temporal and bilateral occipital/parietal areas and working memory capacity. These results suggest the recruitment of a temporo-frontal network in CI users during speech processing and a close connection between ERP effects and cortical activation in CI users. The observed differences in speech-evoked cortical activation patterns for CI users with higher and lower speech intelligibility suggest distinct processing strategies during speech rehabilitation with CI.

OBJECTIVE To evaluate a possible correlation between impedance values and speech perception after cochlear implantation. STUDY DESIGN Retrospective chart review. SETTING Tertiary referral center. PATIENTS AND INTERVENTION All patients implanted with a MedEl Flex28 device in our department with complete audiometric data (Freiburger monosyllabic testing at 65 dB, Hochmaier-Schulz-Moser testing in quiet and in 10 dB noise) and impedance measurements at the 1-year refitting appointment were enrolled in this study. Further inclusion criteria were age > 17 years, native speakers, and no use of electric-acoustic-stimulation. MAIN OUTCOME MEASURES Mean values for impedances were calculated over all electrode contacts and separately for basal, medial, and apical regions. These data were correlated statistically (Pearson's correlation) with speech testing results. Furthermore, groups of patients with extreme values were built and compared against each other and against the rest of the collective. RESULTS Impedance values did not correlate significantly with speech performance in any of the audiometric tests neither for all electrode contacts nor for specific clusters of contacts. Patients with the lowest impedances did not perform statistically different than patients with the highest impedances in any condition. CONCLUSION To our knowledge, this is the first data on a possible correlation between impedances and speech perception. The extent of the impedances as a benchmark for a good performance in speech discrimination tests could not be verified. Further prospective studies, possibly with more precise diagnostic tools, should be carried out to define the value of impedance measurements for cochlear implantation provision.

Background The standard therapy for patients suffering from sensorineural hearing loss is cochlear implantation. The insertion of the electrode array into the cochlea, with potential mechanical trauma and the presence of this foreign body inside the cochlea, may lead to free radical formation and reduced blood perfusion of the cochlea which can result in a loss of residual hearing. Studies have suggested that a particular combination of the antioxidants vitamins A, C and E as well as the vasodilator magnesium (together: ACEMg) may protect the residual hearing. Methods The potential protective effect of ACEMg on residual hearing preservation in cochlear implant (CI) patients was investigated in a single-centre, randomized, placebo-controlled, double-blind phase II clinical trial. CI candidates with some residual hearing in low frequencies receiving MED-EL implants of different FLEX electrode array lengths were treated with ACEMg tablets or placebo respectively 2 days preoperatively and up to 3 months postoperatively. The study objective was to demonstrate that ACEMg is more efficacious than placebo in preserving residual hearing during cochlear implantation by comparing the hearing loss (change in hearing thresholds at 500 Hz from baseline) 3 months after the first fitting between the two treatment groups and to investigate the treatments’ safety. Results Fifty-one patients were included in the study, which had to be terminated before the recruitment goal was reached because of IMP-resupply mismanagement of one partner. In the intention-to-treat population, 25 patients were treated with ACEMg and 24 patients with placebo. The mean hearing loss at 500 Hz was (± 15.84) 30.21 dB (placebo) or (± 17.56) 26.00 dB (ACEMg) 3 months after the initial fitting. Adjusting the postoperative hearing loss for the baseline residual hearing, planned electrode length and surgeon results in 8.01 dB reduced hearing loss in ACEMg-treated patients compared to placebo-treated ones. The safety analysis revealed that ACEMg was generally well-tolerated with adverse event frequencies below the placebo level. Conclusion This is the first clinical trial investigating a drug effect on residual hearing in CI patients. These first-in-man data may suggest that a perioperative oral administration of ACEMg is safe and may provide protection of residual hearing in CI patients. Trial registration EU Clinical Trial Register No. 2012-005002-22. Registered on 6 December 2013. Funding: European Commission FP7-HEALTH-2012-INNOVATION-2.

Purpose Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point. Methods Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests. Results The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis. Conclusion The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.

Objective: Evaluation of speech intelligibility benefit by addition of a temporal masking model to the MP3000 speech coding strategy. Study Design: A crossover design was used to compare variants of the new temporal masking strategy TPACE with respect to the clinical MP3000 strategy. Setting: The study was a prospective, within-subject, repeated-measure experiments.Patients: The study group consisted of 24 postlingually deaf subjects with a minimum of six months experience after CI activation.Intervention: Five conditions were evaluated: The original MP3000 algorithm and the TPACE with four different settings of the temporal masking parameter.Main Outcome Measures: Speech perception test in Comité Consultatif International Téléphonique et Télégraphique (CCITT) noise at 15 to 5 dB SNR. Results: Average speech intelligibility improved with TPACE (T½ = 0.5 ms) by 10 % to 11% compared to MP3000. Conclusion: The addition of temporal masking to the simultaneous masking model of MP3000 could improve the speech intelligibility in noise