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Introduction A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. Methods A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered. Results 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. Conclusions Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

Modulable monosulfonyl squaramides have been shown to exert activation of gold(I) chloride complexes through H-bonding in an intermolecular way. Combinations of (PPh3)AuCl or IPrAuCl complexes and an optimal sulfonyl squaramide cocatalyst bearing two 3,5-bis(trifluoromethyl)phenyl groups efficiently catalyzed diverse heterocyclizations and a cyclopropanation reaction, avoiding in all cases undesired side reactions. Computational studies indicate that the Au–Cl bond breaks by transligation to the triple bond in a ternary complex formed by the actual AuCl···HBD catalyst and the substrate.

IntroductionIn 2017, the first adhesive bone conduction device (aBCD) was introduced. Since then, clinical studies have extensively compared adhesive bone conduction devices to conventional bone conduction systems on softbands. The aim of this study is to evaluate the audiological and subjective outcomes of patients suffering from conductive hearing loss (CHL) who used an aBCD for a trial period, comparing outcomes with their existing passive transcutaneous bone conduction implants (ptBCI), which was either the Sophono Alpha or the BAHA Attract.Material and methodsThis prospective study included 14 congenital aural atresia patients between 7 and 16 years old. Participants had been ptBCI users for at least 2 years and had bone conduction thresholds ≤ 25 dB HL. The aBCD trial was for 1 week. Average pure tone thresholds (PTA4) and word recognition scores (WRS) with disyllabic words at 65 dB SPL in quiet and in noise were measured for each device. Subjective outcomes were recorded using the aBCD mini questionnaire and the SSQ questionnaire for hearing satisfaction, which were filled in by parents.ResultsWe analyzed 16 ears. The mean sound field PTA4 was 52 dB HL unaided, 27 dB HL ptBCI-aided and 29 dB HL aBCD-aided. Mean WRS in quiet was 96% with ptBCI and 95% with BCD. In noise (+5 dB SNR) the mean WRS was 70% with ptBCI and 77% with aBCD. A questionnaire revealed easy handling and good acceptance of the aBCD.ConclusionsIn this group of patients, comparable audiological and subjective satisfaction results were achieved with a non-implantable adhesive bone conduction device. Despite differences in handling, the adhesive BCD presents itself as an alternative to transcutaneous bone conduction implants.

Resumen La tomografia computarizada del hueso temporal es una prueba de imagen fundamental para el diagnostico y tratamiento de diversas entidades que afectan a esta compleja estructura. La tomografia computarizada permite una representacion mas detallada de las estructuras oseas que la resonancia magnetica, lo que determina que sea la prueba de eleccion para la planificacion de la cirugia otologica. El objetivo de este trabajo es el de elaborar una lista de verificacion o checklist que permita al otorrinolaringologo estudiar y valorar de forma sistematica y organizada las principales estructuras de referencia, variantes anatomicas y cambios posquirurgicos mas frecuentes antes de una cirugia segura. Esta revision ha sido promovida por la Sociedad Espanola de Otorrinolaringologia y redactada en un formato de lista de verificacion dividida en las diferentes regiones del hueso temporal y base de craneo lateral.

Purpose To study the evolution of type D personality traits in older adults after cochlear implantation compared with a control group of severely hearing impaired older adults who did not receive a cochlear implant (CI). The influence of COVID-19 on this evolution was also explored. Type D personality combines a high degree of negative affectivity (NA) and social inhibition (SI). Methods In this prospective, longitudinal, controlled multicenter exploratory study, 76 older CI users and 21 severely hearing impaired controls without CI were included. The CI group and the control group did not differ significantly regarding age, formal education, residual hearing, Type D Scale-14 (DS14) total score, NA, and SI at baseline. Type D personality traits were assessed with the DS14 at baseline (T0) and 14 months later (T14). Results Type D personality traits differed significantly over time between the CI group and the control group (p < 0.001). In the CI group, the DS14 total score (mean delta T = -6.63; p < 0.001), NA (mean delta T = -3.26; p < 0.001), and SI (mean delta T = -3.37; p < 0.001) improved significantly over time (delta T = T14-T0), whereas no significant difference was found in the control group. Significantly fewer subjects were categorized as type D personalities in the CI group (delta T = -12; p = 0.023) at T14, whereas no significant change was found in the control group (delta T = 3; p = 0.250). COVID-19 did not influence the evolution of type D personality traits significantly in the CI group. Conclusion Cochlear implantation has a positive effect on type D personality traits in older adults with a severe-to-profound hearing impairment.

Agrofood systems can be described with several interconnected compartments, namely cropland, grassland, livestock and people. For any attempt of optimising or improving the system it is essential to understand each one of them and how they are interrelated.The analysis of these connections improves the general understanding of the full system, helping to identify potential hot spots of production and system leakages in pursuit of sustainability. It is also useful to measure the degree of external dependency or independency, and therefore contributing to assess potential hazards for food security. The GRAFS methodology (General Representation of Agro-food Systems) (Le Noë et al., 2017) allows to represent the mentioned compartments and their connections through material flows.This study starts from the representation of the nitrogen (N) flows of the Spanish agro-food system for the years 1990 to 2015 (Rodríguez et al., 2022). N is considered an adequate component for the analysis because it is essential for crops, livestock and people as part of life-essential molecules, and if not embedded in food and feed, is a potential pollutant.In addition, N, together with water, is the main limiting factor of crop production. But the relationship between N and water goes beyond crop production. Water availability through rain and irrigation significantly affects fertilizer use and nitrogen use efficiency of cropping systems. It also influences N deposition, N fixation, and finally, the net import/export of feed and food due to more demand or excess.Climate change affects precipitation patterns (IPCC, 2022) and the frequency of dry/wet years, even if this variable exhibit higher uncertainty in comparison to other atmospheric variables. The N flows in the systems are expected to be different for dry and wet years, and therefore, different GRAFS can be depicted.The mean accumulated precipitation (PP) in Spain was calculated from the E-OBS database (Cornes et al., 2018) for the 1990-2015 period. Then, dry (PP lower than 85% of mean P) and wet (PP larger than 115% of mean PP) years were identified. The hydrological years were considered (starting on October 1st of the previous year until September 30th).Here, the projections from an ensemble of RCM climate models from the CORDEX project were selected for calculating the frequencies in dry/wet years for both near (around 2050) and far (around 2100) future periods.Then, the frequency in dry, wet and normal years will be used for weighting the GRAFS from the present period to obtain the projected results, which will be analysed in terms of the impacts (e.g., production, external dependency, socioeconomic consequences). The discussion aims to provide insight of possible measures for adapting the Spanish agro-food system to future risks in response to the projected changes.ReferencesCornes et al., 2018. Atmospheres, 123(17): 9391-9409.IPCC, 2022. Climate Change 2022. Sixth Assessment. Cambridge University PressLe Noë et al., 2017. Sci. Total Environ.,586:42-55.Rodríguez et al., 2022. Proc. XXI International N Workshop. ISBN:978-84-122114-6-7

Background Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT). Methods A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies. Results Totally 10 studies (n = 630 patients, average age range: 1–20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29–0.75, all P i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention. Conclusions Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.

Background: Controversy surrounds the routine use of urine culture (UC) in febrile neutropenic children. We aimed to evaluate the need for routine urine studies in febrile neutropenic children with cancer. Procedure: We conducted a prospective study of pediatric cancer patients with urinary continence who presented to the emergency department with febrile neutropenia between 2019 and 2021. Epidemiologic data and clinical and laboratory findings were collected. Urinary tract infection (UTI) was defined as urinary signs/symptoms and positive UC with or without pyuria. Study data were analyzed using descriptive statistics. The diagnostic performance of urinalysis was calculated using positive UC as the gold standard. Results: Positive UC was found in seven of the 205 children included (3.4%; 95% CI 1.4-6-9%), 2 presenting urinary symptoms. UTI prevalence was 1.0% (95% CI 0.1-3.5). A 23.8% prevalence of positive UC was found in patients with urinary symptoms and/or history of urinary tract disease (95% CI 8.2-47.2%) as compared to 1.1% of those without symptoms or history (95% CI 0.1-3.9%) (pConclusions: UTI is an infrequent cause of infection in these patients. Urinalysis is indicated only in febrile neutropenic children with urinary signs/symptoms and in asymptomatic patients with a history of urinary tract disease. When urine is collected, UC should be requested regardless of the result of the urinalysis.

Purpose: (a) To measure the change in cognition, the improvement of speech perception, and the subjective benefit in people under and over 60 years following cochlear implantation. (b) To assess the relationship between cognition, demographic, audiometric, and subjective outcomes in both age groups. Methods: 28 cochlear implant (CI) users were assigned to the < 60y group and 35 to the ≥ 60y group. Cognition was measured using the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing impaired individuals (RBANS-H); subjective benefit was measured using the Nijmegen Cochlear Implant Questionnaire (NCIQ); the Glasgow Benefit Inventory (GBI); the Hearing Implant Sound Quality Index (HISQUI19); Speech, Spatial and Qualities of Hearing Scale (SSQ12); and the Hospital Anxiety and Depression Scale (HADS). Results: Prior to surgery: the RBANS-H total score positively correlated with the domains “Advanced sound”, “Self-esteem”, and “Social functioning” of NCIQ, and negatively with HADS scores. 12 months post-implantation: the RBANS-H total score increased in the < 60y (p = 0.038) and in the ≥ 60y group (p < 0.001); speech perception and subjective outcomes also improved; RBANS-H total score positively correlated with “Self-esteem” domain in NCIQ. Age and the RBANS-H total score correlated negatively in the ≥ 60y group (p = 0.026). Conclusions: After implantation, both age groups demonstrated improved cognition, speech perception and quality of life. Their depression scores decreased. Age was inversely associated with cognition., This work was supported by a grant (PI16/00079) from Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I, ISCiii, Spain. The authors would like to thank the subjects for their participation, and Angelina Gurkina for their medical writer assistance

Background Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO + ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies. Methods Patients (N = 166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts). Secondary endpoints included other efficacy metrics and safety. Exploratory endpoints included pharmacokinetics and biomarker analyses. Results As of January 13, 2021, median OS (80% CI) was 11.7 (10.3–16.5) and 10.8 (9.1–15.8) months with NIVO and NIVO + IPI, respectively, in newly diagnosed DIPG. Median PFS (80% CI) with NIVO and NIVO + IPI was 1.7 (1.4–2.7) and 1.3 (1.2–1.5) months, respectively, in recurrent/progressive high-grade glioma; 1.4 (1.2–1.4) and 2.8 (1.5–4.5) months in relapsed/resistant medulloblastoma; and 1.4 (1.4–2.6) and 4.6 (1.4–5.4) months in relapsed/resistant ependymoma. In patients with other recurrent/progressive CNS tumors, median PFS (95% CI) was 1.2 (1.1–1.3) and 1.6 (1.3–3.5) months, respectively. Grade 3/4 treatment-related adverse-event rates were 14.1% (NIVO) and 27.2% (NIVO + IPI). NIVO and IPI first-dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor programmed death ligand 1 expression was not associated with survival. Conclusions NIVO ± IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals.

PURPOSE Pediatric neuro-oncology resources are mostly unknown in Chile. We report the human and material resources available in Chilean hospitals providing pediatric neuro-oncology services. METHODS A cross-sectional survey was distributed to 17 hospitals providing pediatric neuro-oncology services (Programa Infantil Nacional de Drogas Antineoplásicas [PINDA] hospitals, 11; private, 6). RESULTS Response rate was 71% (PINDA, 8; private, 4). Pediatric neuro-oncology services were mainly provided within general hospitals (67%). Registries for pediatric CNS tumors and chemotherapy-related toxicities were available in 100% and 67% of hospitals, respectively. CNS tumors were treated by pediatric oncologists in 92% of hospitals; none were formally trained in neuro-oncology. The most used treatment protocols were the national PINDA protocols. All WHO essential medicines for childhood cancer were available in more than 80% of the hospitals except for gemcitabine, oxaliplatin, paclitaxel, and procarbazine. The median number of pediatric neurosurgeons per hospital was two (range, 2-6). General neuroradiologists were available in 83% of the centers. Pathology specimens were sent to neuropathologists (58%), adult pathologists (25%), and pediatric pathologists (17%). Intensity-modulated radiotherapy, conformal radiotherapy, and cobalt radiotherapy were used by 67%, 58%, and 42% of hospitals, respectively. Only one private hospital performed autologous hematopoietic cell transplant for children with CNS tumors. CONCLUSION A wide range of up-to-date treatment modalities are available for children with CNS tumors. Our survey highlights future directions to improve the pediatric neuro-oncology services available in Chile such as the expansion of multidisciplinary clinics, palliative care services, long-term cancer survivorship programs, dedicated clinical research support teams, establishing standardized mechanism for sending pathologic specimen for second opinion to international specialized centers, and establishing specialized neuro-oncology training program.

A cross-sectional nationwide study was designed to assess national compliance with international consensus/guidelines of monitoring asparaginase levels in children with acute lymphoblastic leukemia (ALL) treated with asparaginase in routine clinical practice.An ad hoc questionnaire was designed and completed by staff physicians from Hemato-Oncology Units throughout Spain.A total of 39 physicians (64% pediatricians) with a mean (SD) age 43.5 (7.9) years and 15.3 (17.6) years of professional activity participated in the study. They accounted for 90% of hospitals in which children with ALL are treated in Spain. A total of 19 participants (48.7%) reported that asparaginase levels were routinely monitored (own center in 2 cases [10.5%], another hospital in 17 cases [89.5%]). Asparaginase was not monitored in 51.3% of the cases, mostly (80%) because unavailability of testing. When asparaginase was monitored, 68% of participants reported that this was done in all asparaginase-treated patients and 84% in all phases of the disease (induction, consolidation, re-induction, maintenance) with a time interval of 7 days for the pegylated form, 48 h for Erwinia asparaginase and 14 days for maintenance with the pegylated form. All participants reported that they modified treatment according to results of testing, with a limit of total depletion of ≥100 IU/L. Levels100 or 20 IU/L were considered indicative of hypersensitivity by 46% of physicians.There is still a gap between what is recommended and what is done in clinical practice, with more than 50% of centers not monitoring the level of asparaginase activity in pediatric ALL. Protocols for asparaginase testing in daily practice should be implemented.

Irrigation, one of the 28 agri-environmental indicators defined in the European Common Agricultural Policy, is often neglected in agricultural nitrogen (N) budgets, while it can be a considerable source of N in irrigated agriculture. The annual N input from irrigation water sources (NIrrig) to cropping systems was quantified for Europe for 2000–2010 at a resolution of 10 × 10 km, accounting for crop-specific gross irrigation requirements (GIR) and surface- and groundwater nitrate concentration. GIR were computed for 20 crops, while spatially explicit nitrate concentration in groundwater was derived using a random forest model. We show that although GIR were relatively stable (46–60 km3 yr-1), the Nirrig in Europe increased over the 10-year period (184 to 259 Gg N yr-1), approximately 68 % of which occurred in the Mediterranean region. The main hotspots appeared in areas with both high irrigation requirements and high groundwater nitrate concentration, reaching up to averaged values of 150 kg N ha-1 yr1. These were mainly located in Mediterranean Europe (Greece, Portugal and Spain) and to a lesser extent in Northern Europe (The Netherlands, Sweden and Germany). By not including NIrrig, environmental and agricultural policies are underestimating the real extent of N pollution hotspots in European irrigated systems.

Introduction: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, infection prevention measures were enforced at our Pediatric Neuro-Oncology unit. Methods: A retrospective study analyzing patients booked in this unit during lockdown was performed to describe its performance. Results: There were 438 consultations for 123 patients (320 on-site/118 telephone). Eight new diagnoses were made, with one significant delay. Only one patient tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delay in imaging testing occurred in 15 patients. Chemotherapy was delayed in one case. There were no delays in radiotherapy. Conclusions: Measures implemented were effective in minimizing the risk of COVID-19 infection, achieving continuity in diagnoses and treatment, and avoiding delays that could impact survival.

PURPOSE Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.

Resumen Introduccion El diagnostico de las fracturas del hueso temporal (FHT) se basa en la imagen radiologica. La clasificacion mas utilizada divide las fracturas en longitudinales, transversales y mixtas. En los ultimos anos han surgido otras clasificaciones con el objeto de predecir mejor las manifestaciones clinicas. Objetivos Revisar las imagenes de tomografia computarizada (TC) del hueso temporal, definir su patron radiologico segun la clasificacion tradicional y estudiar la concordancia interobservador de los hallazgos encontrados con los descritos en el informe radiologico. Analizar la asociacion entre los tipos de fractura y los hallazgos clinicos. Estudiar el impacto de la neumatizacion mastoidea en las caracteristicas de la fractura. Materiales y metodos Estudio retrospectivo de 110 FHT diagnosticadas mediante TC entre enero de 2016 y mayo 2019. Resultados Se identificaron 52 fracturas transversales (47%), 34 longitudinales (30%) y 19 mixtas (17%) con buena concordancia interobservador (k = 0,637). Las fracturas longitudinales se asociaron con hipoacusia de transmision (p Conclusiones La clasificacion tradicional de las FHT es reproducible. Su asociacion con los hallazgos clinicos mejora cuando se analiza ademas la afectacion de la capsula otica. La neumatizacion mastoidea no es un factor protector para las FHT ni para la afectacion de la capsula otica.

Input–output estimates of nitrogen on cropland are essential for improving nitrogen management and better understanding the global nitrogen cycle. Here, we compare 13 nitrogen budget datasets covering 115 countries and regions over 1961–2015. Although most datasets showed similar spatiotemporal patterns, some annual estimates varied widely among them, resulting in large ranges and uncertainty. In 2010, global medians (in TgN yr−1) and associated minimum–maximum ranges were 73 (64–84) for global harvested crop nitrogen; 161 (139–192) for total nitrogen inputs; 86 (68–97) for nitrogen surplus; and 46% (40–53%) for nitrogen use efficiency. Some of the most uncertain nitrogen budget terms by country showed ranges as large as their medians, revealing areas for improvement. A benchmark nitrogen budget dataset, derived from central tendencies of the original datasets, can be used in model comparisons and inform sustainable nitrogen management in food systems. Existing datasets of nitrogen (N) balance in agriculture are often discrepant. Comparing 13 of them regarding five metrics (fertilizer application, manure application, biological N fixation, atmospheric deposition, and N harvested as crop products) over 1961–2015 reveals why. Recommendations for improving N quantification and an N budget benchmark dataset are also proposed.

Global projections indicate that approximately 500 Mha of new arable land will be required to meet crop demand by 2050. Applying a dynamic phosphorus (P) pool simulator under different socioeconomic scenarios, we find that cropland expansion can be avoided with less than 7% additional cumulative P fertilizer over 2006–2050 when comparing with cropland expansion scenarios, mostly targeted at nutrient-depleted soils of sub-Saharan Africa. Additional P fertilizer would replenish P withdrawn from crop production, thereby allowing higher productivity levels. We also show that further agronomic improvements such as those that allow for better (legacy) P use in soils could reduce both P outflows to freshwater and coastal ecosystems and the overall demand for P fertilizer. Population growth and associated increases in food and feed demand may drive cropland expansion at the expense of natural area and biodiversity, as well as higher greenhouse gas emissions. This study shows how a more efficient and better targeted use of phosphorus is key to avoiding such environmental problems.

This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.

Hearing loss has been identified as a major modifiable risk factors for dementia. Adult candidates for cochlear implantation (CI) represent a population at risk of hearing loss-associated cognitive decline. This study investigated the effect of demographics, habits, and medical and psychological risk factors on cognition within such a cohort. Data from 34 consecutive adults with post-lingual deafness scheduled for CI were analyzed. Pure tone audiometry (PTA4) and Speech Discrimination Score (SDS) were recorded. The Repeatable Battery for Assessment of Neuropsychological Status for Hearing impaired individuals (RBANS-H) was used to measure cognition. Demographics (sex, age, years of education), habits (smoking, alcohol intake, physical inactivity), and medical factors (hypertension, diabetes, traumatic brain injury) were evaluated. Depression was measured using the Hospital Anxiety and Depression Scale (HADS), and social inhibition with the Type D questionnaire (DS14). All participants (mean age 62 ± 15 years) suffered from severe to profound hearing loss (PTA4:129 ± 60 dB; SDS:14 ± 24%). The mean RBANS-H total score was 83 ± 16. Participants reported a mean of years of formal education of 12 ± 5 years. The prevalence of habits and medical risk factors was: physical inactivity (29%), body mass index >30 (28%), traumatic brain injury (25%), hypertension (24%), heavy alcohol consumption (13%), smoking (13%), and diabetes (0%). Regarding psychological factors, the mean scores of social inhibition and depression were 10 ± 6 and 6 ± 5, respectively. The number of years of education was significantly correlated with the RBANS-H total score (p p = 0.003), “Visuospatial/constructional” (p p p = 0.008). Physical inactivity was associated with lower scores in the “Delayed memory” (p = 0.031); hypertension correlated with lower RBANS-H total scores (p = 0.025) and “Attention” (p = 0.006). Depression and social inhibition were negatively correlated with RBANS-H total score and with the “Immediate memory,” “Visuospatial/constructional,” and “Attention” (all p

Greenhouse gas emissions embodied in international trade have risen sharply over the last few decades because of the globalization of economies and countries’ productive specialization. We have built a model able to trace all agro-food emissions along global value chains for 1986–2013. The results show that while the domestic fraction of food emissions has slightly decreased, the foreign fraction has grown by 75%, accounting for 24% of all agro-food emissions today. A few supply chains concentrate most of this increase, with consumption of animal products explaining 70% of all embodied emissions in trade. It was also found that higher incomes resulted in higher percentages of foreign agro-food emissions, and that increasing the proportion of imports in these footprints can be associated with lower per capita emissions. Because trade increasingly redistributes agro-food emissions around the world, national mitigation efforts should be complemented with strong international and coordinated cooperation actions.

Introducción y objetivo: Los videos, como material didáctico complementario, pueden reemplazar parte de las horas de docencia y ayudar en la adquisición de conocimientos en Otorrinolaringología. Para ello se pretende analizar el impacto de la visualización de 4 videos en el resultado de 6 preguntas específicas del examen teórico de la asignatura y evaluar la percepción de estos videos. Método: Estudio analítico cuasi experimental transversal realizado en 213 estudiantes de Otorrinolaringología de la Universidad Autónoma de Madrid divididos en 2 grupos: grupo intervención y grupo control. Las diferencias en el rendimiento en las 6 preguntas entre ambos grupos se determinaron mediante la prueba χ² o el test exacto de Fisher, con un valor de significación p

An efficient dynamic kinetic resolution (DKR) approach for the synthesis of axially chiral diamines has been developed on the basis of a ruthenium-catalyzed enantioselective transfer hydrogenation....

α-Keto hydrazones behave as suitable precursors of nucleophilic β-amino aza-dienamine intermediates. Using a multifunctional tert-Leucine derived amino-thiourea as the catalyst, this reactivity was exploited to perform asymmetric 1,4-addition to nitroalkenes, affording densely functionalized products with excellent yields and enantioselectivities. Ensuing efficient and selective transformations provide valuable derivatives such as γ-nitrobutyric acids and functionalized pyrrolidines. Aggregation studies support the key role of the tert-Leucine fragment in the catalyst and the benzoic acid as co-catalyst, promoting disaggregation of thiourea dimers to generate (thiourea–NH3+)(PhCOO−) ion pairs as catalytically relevant species. The formation of a highly ordered supramolecular ion pair complex [(heterochiral) Ia–NH3+/PhCOO−]2 accounts for the strong non-linear effect observed. A DFT study of the catalytic cycle revealed the formation of the intermediate enamine as the rate-limiting step. A suitable stereochemical model was proposed, further supported by a quantitative analysis of the non-covalent interactions (NCI analysis).

The Sunnybrook facial grading system (SFGS) is one of the most widely employed tools to assess facial function. The present study aimed to determine the validity and reliability of the Spanish language version of the SFGS.Forward-backward translation from the original English version was performed by fluent speakers of English and Spanish. Videos from 65 patients with facial paralysis (FP) were evaluated twice by five otolaryngologists with experience in FP evaluation. Internal consistency and intra- and inter-rater reliability were assessed. The House-Brackmann scale was used to display concurrent validity which was established by Spearman's rho correlation.The Cronbach's α score exceeded 0.70. The intra-rater intraclass correlation coefficient (ICC) was nearly perfect for the composite score (0.96-0.99), voluntary movements (0.97-0.99), and synkinesis (0.91-0.98), and important to almost perfect for symmetry at rest (0.79-0.97). In both evaluations, the inter-rater ICC was higher than 0.90 for the composite score (0.92-0.96) and voluntary movements (0.91-0.96) and slightly lower for symmetry at rest (0.66-0.85) and synkinesis (0.72-0.87). A strong negative correlation was found between the H-B scale and SFGS (Spearman's rho coefficient = - 0.92, p 0.001) in both evaluations.The Spanish version of the SFGS is a reliable and valuable instrument for the assessment of facial function in the diagnosis and treatment of patients with FP.

The management of facial paralysis following skull base surgery is complex and requires multidisciplinary intervention. This review shows the experience of a facial nerve (FN) unit in a tertiary university referral center. A multidisciplinary approach has led to the breaking of some old treatment paradigms. An overview of five FN scenarios is presented. For each setting a contemporary approach is proposed in contrast to the established approach. 1) For patients with an anatomically preserved FN with no electrical response at the end of surgery for vestibular schwannoma, watchful waiting is usually advocated. In these cases, reinforcement with an interposed nerve graft is recommended. 2) In cases of epineural FN repair, with or without grafting, and a poor expected prognosis, an additional masseter-to-facial transfer is recommended. 3) FN transfer, mainly hypoglossal-to-facial and masseter-to facial, are usually chosen based on the surgeons' preference. The choice should be based on clinical factors. A combination of techniques improves the outcome in selected patients. 4) FN reconstruction following malignant tumors requires a combination of parotid and temporal bone surgery, involving different specialists. This collaboration is not always consistent. Exposure of the mastoid FN is recommended for lesions involving the stylomastoid foramen, as well as intraoperative FN reconstruction. 5) In patients with incomplete facial paralysis and a skull base tumor requiring additional surgery, consider an alternative reinnervation procedure, "take the FN out of the equation" before tumor resection. In summary, to achieve the best results in complex cases of facial paralysis, a multidisciplinary approach is recommended.

Objective To compare the cognitive evolution of older adults with severe or profound hearing impairment after cochlear implantation with that of a matched group of older adults with severe hearing impairment who do not receive a cochlear implant (CI). Design In this prospective, longitudinal, controlled, and multicenter study, 24 older CI users were included in the intervention group and 24 adults without a CI in the control group. The control group matched the intervention group in terms of gender, age, formal education, cognitive functioning, and residual hearing. Assessments were made at baseline and 14 months later. Primary outcome measurements included the change in the total score on the Repeatable Battery for the Assessment of Neuropsychological Status for Hearing impaired individuals score and on its subdomain score to assess cognitive evolution in both groups. Secondary outcome measurements included self-reported changes in sound quality (Hearing Implant Sound Quality Index), self-perceived hearing disability (Speech, Spatial, and Qualities of Hearing Scale), states of anxiety and depression (Hospital Anxiety and Depression Scale), and level of negative affectivity and social inhibition (Type D questionnaire). Results Improvements of the overall cognitive functioning (p = 0.05) and the subdomain "Attention" (p = 0.02) were observed after cochlear implantation in the intervention group; their scores were compared to the corresponding scores in the control group. Significant positive effects of cochlear implantation on sound quality and self-perceived hearing outcomes were found in the intervention group. Notably, 20% fewer traits of Type D personalities were measured in the intervention group after cochlear implantation. In the control group, traits of Type D personalities increased by 13%. Conclusion Intervention with a CI improved cognitive functioning (domain Attention in particular) in older adults with severe hearing impairment compared to that of the matched controls with hearing impairment without a CI. However, older CI users did not, in terms of cognition, bridge the performance gap with adults with normal hearing after 1 year of CI use. The fact that experienced, older CI users still present subnormal cognitive functioning may highlight the need for additional cognitive rehabilitation in the long term after implantation.

Resumen Introduccion El tratamiento de la paralisis facial periferica con toxina botulinica es seguro y eficaz. Si bien es conocido su impacto beneficioso sobre la calidad de vida de los pacientes, hasta ahora no se ha estudiado especificamente su percepcion subjetiva. Nuestro objetivo ha sido conocer los resultados del tratamiento con toxina botulinica centrandonos en la opinion del paciente. Pacientes y metodo Estudio prospectivo realizado en una muestra aleatoria de pacientes con secuelas de paralisis facial periferica, que estaban siendo tratados con toxina botulinica en el Servicio de Medicina Fisica y Rehabilitacion de nuestro hospital. Creamos un cuestionario sencillo para evaluar tanto la satisfaccion como la percepcion subjetiva de mejoria despues del tratamiento con toxina botulinica. Resultados Despues de la infiltracion, el 95% de los pacientes se sentia bien o muy bien. Mas del 80% de ellos noto mejoria respecto a la sensacion de tirantez en la mejilla y el cuello. Alrededor de 3/4 partes de los pacientes percibieron mejoria en el rango de movilidad voluntaria y en aproximadamente el 80% mejoraron las sincinesias. Casi todos ellos volverian a tratarse si se les propusiera de nuevo y el 100% recomendaria la infiltracion con toxina botulinica a otros pacientes con paralisis facial Conclusiones El tratamiento con toxina botulinica proporciona una mejora subjetiva importante en los pacientes con secuelas de paralisis facial periferica, tanto en reposo como respecto al control de sincinesias. El grado de satisfaccion es superior a 8/10 en el 99% de los pacientes estudiados.

Analysis of head magnetic resonance images (MRI) of patients with active bone conduction implants (BCIs) is challenging. Currently, there are two generations of the transcutaneous Bonebridge system (BCI601 and BCI602), the main difference between them being the transducer design and thickness. The aim was to compare the effect of transducer placement and artifact reduction sequences on legibility of MRI scans. Four Thiel-fixed human head specimens were used: BCI601 was implanted in sinodural and middle fossa placement, and BCI602 in middle fossa and retrosigmoid approach. Images were obtained with a Signa® 1.5T MR. A metal artifact reduction sequence known as MAVRIC (multiacquisition variable-resonance image combination) was used. Each specimen was scanned using standard axial T2 SE and compared with axial MAVRIC artifact reduction sequences. Qualitatively, limits of the artifact produced by the implant were better defined with MAVRIC than with standard T2 sequences. Assessment of contralateral internal auditory canal (IAC) was possible in all cases. Placement of the BCI602 in the middle fossa allowed the view of the ipsilateral IAC using MAVRIC sequence. Quantitatively, the artifact was reduced with MAVRIC sequence from 6.3 to 59.7%, depending on the position of implant and model; the middle fossa placement and the BCI602 being those generating shorter artifact radio. Artifact optimized sequences as MAVRIC reduce the artifact caused by the Bonebridge system. The middle fossa approach allows a better visualization of IAC canal in the ipsilateral ear with both implant versions, but the effect is more prominent with the BCI602.

Background: Facial nerve tumors (FNTs) are relatively rare benign lesions that arise from any segment of the facial nerve (FN). About half of all patients present with FN dysfunction, mainly long-standing or progressive facial paralysis. Diagnosis of an FNT is usually based on radiological imaging and confirmed by histological study. Most reported cases of FNTs are schwannomas and hemangiomas. Objectives: The aim of this study was to review 4 cases of lesions with clinical, radiological, and surgical findings that suggested an FNT, the pathology revealing a fibrovascular proliferation with no clear signs of a specific tumor. Method: Medical records of patients who had surgery due to an FN lesion were reviewed. Cases with known tumoral lesions were excluded. Four patients with tumor-like lesions were identified. Their imaging studies were re-evaluated. The pathological study included hematoxylin-eosin, Masson’s trichrome, and immunohistochemistry for S100 protein, neurofilaments, CD31, Wilms’ tumor 1 (WT1), and D240. Results: The 4 cases revealed tumor-like fibrovascular lesions that could not be classified as typical pathological entities. All cases had a complete facial palsy preoperatively. Computed tomography and magnetic resonance imaging (MRI) suggested schwannoma or hemangioma. A complete excision was achieved, and a facial reconstruction was performed immediately after interruption. Postoperative FN function was improved in all cases. The histological study showed nervous tracts of normal morphology, with fibrous and vascular tissue interspersed in variable proportions. All cases showed areas of fibrosis with Masson’s stain. In all cases, nervous tissue and Schwann cells tested positively for neurofilaments and S100, respectively. In vascular areas, endothelial cells stained positively for CD31, and negatively for D240 and WT1. Conclusions: Fibrovascular lesions of the FN may mimic primary FNTs, especially schwannomas and hemangiomas. Surgical excision with grafting or nerve transfer is the procedure of choice if a complete facial paralysis is found. This unusual condition should be considered when counseling patients with FN lesions. The lack of hyperintensity on MRI T2-weighted images may suggest the presence of fibrous tissue.

Medulloblastoma (MB) is a malignant embryonal tumor that develops especially in childhood, with overall survival (OS) at 5 years of up to 70%. The objective of this study is to analyze treatment delivery variables in a retrospective cohort and evaluate the impact of these treatment quality parameters on survival. From 2000 to 2018, 40 pediatric patients with medulloblastoma, treated according to current international protocols, were retrospectively analyzed. Treatment delivery quality indicators were analyzed including the extent of surgery, radiotherapy (RT) parameters, and chemotherapy variables, related with time and dose-intensity deviations. With a median follow-up of 74 months (range, 6-195), OS at 5 years was 74 ± 7%, 81 ± 8% for standard-risk, and 55 ± 16% for high-risk patients (p = 0.090). Disease-free survival at 5 years was not significantly affected by extent of surgery (p = 0.428) and RT-related variables such as surgery-RT interval (p = 0.776) neither RT duration (p = 0.172) or maintenance chemotherapy compliance (p = 0.634). Multivariate analysis identified risk groups predictive of worse DFS (p = 0.032) and leptomeningeal dissemination associated with inferior OS (p = 0.029).Conclusion: Treatment delivery optimization has improved survival rates of patients with MB. Despite this, in our study, we have not established a clear influence of the considered radiotherapy and chemotherapy treatment quality parameters on outcomes. What is Known: • Improvement in treatment modalities during the last decades has reached a 5-year OS of up to 70% in these patients. • Extent of resection and radiotherapy parameters such as interval between surgery-radiotherapy and radiotherapy duration has been described as probable survival prognostic factors. What is New: • Differences in medulloblastoma survival rates between prospective studies and retrospective series. • The impact on survival of the three main treatment variables, surgery, radiotherapy and chemotherapy, susceptible to improvement.

Purpose To evaluate the safety and performance of three novel vibroplasty couplers that allow attachment of the floating mass transducer of a transcutaneous active middle ear implant (AMEI) to the round window (RW) membrane, the long process (LP), or the incus body and the short process (SP) of the incus. Methods Retrospective multicenter cohort study of 25 AMEI users with sensorineural or mixed hearing loss that were among the first implanted with an AMEI vibrating ossicular prosthesis in combination with the third generation of vibroplasty couplers between 2014 and 2016. Main Outcome Measures were bone-conduction pure-tone and vibroplasty thresholds, postoperative aided sound field thresholds and postoperative aided word recognition score (WRS). Results Bone conduction threshold changes of more than 10 dB in 4PTABC were observed in two subjects. A mean improvement of 57.8% in speech recognition was observed with a mean WRS at 65 dB SPL improving from 14.8% (SD 21.9%) preoperatively to a mean aided score of 72.6% (SD 18.6%). Sound field thresholds improved from an average 4PTASF of 64.1 dB HL (SD 9.8 dB HL) to 37.0 dB HL (SD 8.9 dB HL), resulting in a mean functional gain of 27.1 dB. There was no significant difference in WRS or functional gain between the coupler types. Conclusion Initial experience shows that all three third generation vibroplasty couplers represent safe and efficient attachment options for the FMT allowing the surgeon to choose the coupling type based on the present pathology.