Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

PURPOSE: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age. METHODS: Relevant intergroup statistics were used to identify differences in tumour, treatment and outcome characteristics based on age with elderly patients (EP) defined as age 65 years and over. Survival was estimated using the Kaplan Meier method. RESULTS: Of the combined 205 patients, 57 (28%) were EP. Of these, 95% were ECOG 0-1 and 65% underwent macroscopic resection compared with 97% and 61% of younger patients (YP) respectively. There were numerically less MGMT-methylated (56% vs. 63%, p = 0.4) and IDH-mutated (4% vs. 13%, p = 0.1) tumours in EP vs. YP. Following surgery, EP were more likely to receive short course chemoradiation (17.5% vs. 6%, p = 0.017). At recurrence, EP tended to receive or best supportive care (28.3% vs. 15.4%, p = 0.09) or non-surgical options (96.2% vs. 84.6%, p = 0.06), but were less likely to receive bevacizumab (23.1% vs. 49.5%, p < 0.01). Median PFS was similar at 9.3months in EP and 8.5months in YP, with similar median OS at 20months. CONCLUSION: In this trial population of predominantly fit EP, survival was similar to YP despite a proportion receiving less aggressive therapy at diagnosis and recurrence. Advancing age does not appear to be an adverse prognostic factor for glioblastoma when patients are fit for treatment, and a less aggressive approach in selected patients may not compromise outcomes.

Checklist como herramienta para los padres ante la fiebre en el paciente pediátrico / Facing fever in the pediatric patient: Checklist as a tool for parents

Introducción: En Europa occidental el 20-40% de los niños con fiebre solicitan asistencia sanitaria. La mayoría presentan infecciones virales banales, sin embargo, es esencial en pediatría distinguir los pacientes que presentan una infección severa. Este proceso se inicia con el reconocimiento de la gravedad y la posterior búsqueda de atención médica por parte de los padres. Metodología: Estudio observacional analítico y transversal. Se seleccionaron 100 pacientes en 2 centros de salud. Se recogieron los datos sociodemográficos, junto con las respuestas de un checklist que contenía los signos y los síntomas ante los que solicitar asistencia sanitaria en caso de fiebre. Posteriormente se rellenó el checklist por parte del pediatra. Resultados: La edad media de los pacientes fue de 5,41 años. El 50% consultó en las primeras 48h de evolución de la fiebre. En el 42% la respuesta a todos los ítems del checklist fue exactamente la misma entre acompañante y pediatra. No existieron diferencias significativas según variables: primer episodio de fiebre (p=0,262), edad del paciente (p=0,859), tener hermano/as (p=0,880), parentesco familiar del acompañante (p=0,648) o grado de estudios del acompañante (p=0,828). Conclusiones: Las consultas médicas por fiebre en pediatría se realizan muy precozmente. Un alto porcentaje no presentan signos de alarma cuando consultan. Se plantea la necesidad ampliar la formación sobre los signos de alarma de la fiebre en todos los padres, independientemente del número de hijos, de la edad o del nivel educacional. El checklist como herramienta para la valoración en el domicilio de la fiebre ha recibido una alta puntuación en su utilidad.(AU)

Introduction: In Western Europe, 20%-40% of children with fever request health care. Most of them present trivial viral infections, however, it is essential in pediatrics to distinguish patients who present a severe infection. This process begins with the recognition of the seriousness and the subsequent search for medical attention by the parents. Methodology: Analytical and cross-sectional observational study. One hundred patients were selected in two health centers. Sociodemographic data were collected, together with the responses to a checklist containing the signs and symptoms to request health care in case of fever. Subsequently, the checklist was filled out by the pediatrician. Results: The mean age of the patients was 5.41 years. 50% consulted in the first 48h of fever evolution. In 42%, the response to all the items on the checklist was exactly the same between the companion and the pediatrician. There were no significant differences according to variables: first episode of fever (P=.262), age of the patient (P=.859), having a sibling (P=.880), family relationship of the companion (P=.648) or educational level of the companion (P=.828). Conclusions: Medical consultations for fever in pediatrics are carried out very early. A high percentage do not present alarm signs when they consult. There is a need to expand training on the alarm signs of fever in all parents, regardless of the number of children, age or educational level. The checklist as a tool for home assessment of fever has received high marks for its usefulness.(AU)

[Risk factor control, lifestyle intervention, and prescribed medication in a cohort of patients with ischemic heart disease]. / Control sobre factores de riesgo, intervención sobre estilos de vida, y medicación prescrita en una cohorte de pacientes con cardiopatía isquémica.

OBJECTIVE: The aim of this study was to analyze the recommended prevention measures in our health area for patients discharged after a myocardial infarction. METHODS: This was a retrospective descriptive study that selected patients with acute coronary syndrome in our health area in the previous calendar year. Control of the risk factors observed at the time of the coronary event and at 1 year and medication prescribed 1 year after the episode were studied. Variables including age, sex, control of dyslipidemia, hypertension or diabetes mellitus, adherence to treatment and lifestyle habits were analyzed. RESULTS: Risk factor control was insufficient and sometimes even unassessed at the time of infarction. Although a slight improvement was perceived, control remained insufficient 1 year later. Moreover, patients, particularly women, were undertreated: one fifth (20%) more men were receiving appropriate treatment than women year after the myocardial event. CONCLUSIONS: An additional effort must be made compared to what is currently being done, both by specialists in Hospital Care and Primary Care, to carry out good control of risk factors, meaning the control of certain diseases such as diabetes, high blood pressure or dyslipidemia, as well as habits or lifestyles that increase the probability of suffering a cardiovascular event. Furthermore, it is important to avoid these cardiovascular diseases and their relapse to reinforce adherence to the prescribed treatments.

Raising awareness of the important role of engineering in sustainable development.

STEAM (Science, Technology, Engineering, Arts and Mathematics) professions play a crucial role in transforming 21st-century society, as they contribute to developing new technologies that support the achievement of the Sustainable Development Goals (SDGs). Aligning engineering education with sustainable development requires raising awareness among students, fostering commitment among future generations of engineers, and promoting technical vocations. In this paper, an educational experience designed with these objectives is presented, in which more than 130 students from five undergraduate degrees in engineering and architecture at the Higher Polytechnic School of Zamora (HPSZ) of the University of Salamanca actively participated. To carry out the project, an online course was designed to train all participating students on general aspects of the 2030 Agenda, and research works were proposed in the ten involved degree subjects. The assessment of students' prior knowledge and learning regarding the 2030 Agenda was conducted through an objective multiple-choice pre-test and post-test. Additionally, their satisfaction with this educational experience was assessed through a questionnaire. The results revealed a considerable improvement in the students' knowledge of the general contents of sustainable development, especially after participating in classroom debate sessions. The initial objective test showed a low average score, indicating the lack of knowledge about the 2030 Agenda and the SDGs among engineering students. However, the final objective test revealed a significant improvement of 3 points out of 10. Regarding the research works, out of a total of 91 students, 53 papers addressing complex issues related to sustainable development and current engineering solutions were presented. This approach facilitated collaborative learning and the celebration of World Engineering Day at the HPSZ. The results of the satisfaction survey demonstrated that the experience was positive for both students and faculty Furthermore, its media impact was essential for increasing engineering vocations' visibility and social recognition.

Incidence of childhood cancer in Latin America and the Caribbean: coverage, patterns, and time trends / Incidencia del cáncer infantil en América Latina y el Caribe: cobertura de los registros, patrones y tendencias a lo largo del tiempo / Incidência de câncer infantil na América Latina e no Caribe: cobertura, padrões e tendências temporais

ABSTRACT Objective. To provide a comprehensive overview of geographical patterns (2001-2010) and time trends (1993-2012) of cancer incidence in children aged 0-19 years in Latin America and the Caribbean (LAC) and interpret the findings in the context of global patterns. Methods. Geographical variations in 2001-2010 and incidence trends over 1993-2012 in the population of LAC younger than 20 years were described using the database of the third volume of the International Incidence of Childhood Cancer study containing comparable data. Age-specific incidence per million person-years (ASR) was calculated for population subgroups and age-standardized (WSR) using the world standard population. Results. Overall, 36 744 unique cases were included in this study. In 2001-2010 the overall WSR in age 0-14 years was 132.6. The most frequent were leukemia (WSR 48.7), central nervous system neoplasms (WSR 23.0), and lymphoma (WSR 16.6). The overall ASR in age group 15-19 years was 152.3 with lymphoma ranking first (ASR 30.2). Incidence was higher in males than in females, and higher in South America than in Central America and the Caribbean. Compared with global data LAC incidence was lower overall, except for leukemia and lymphoma at age 0-14 years and the other and unspecified tumors at any age. Overall incidence at age 0-19 years increased by 1.0% per year (95% CI [0.6, 1.3]) over 1993-2012. The included registries covered 16% of population aged 0-14 years and 10% of population aged 15-19 years. Conclusions. The observed patterns provide a baseline to assess the status and evolution of childhood cancer occurrence in the region. Extended and sustained support of cancer registration is required to improve representativeness and timeliness of data for childhood cancer control in LAC.

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RESUMO Objetivo. Apresentar uma visão abrangente dos padrões geográficos (2001 a 2010) e das tendências temporais (1993 a 2012) da incidência de câncer em crianças e jovens de 0 a 19 anos na América Latina e no Caribe (ALC) e interpretar os resultados no contexto de padrões mundiais. Métodos. Foram descritas variações geográficas de 2001 a 2010 e tendências de incidência de 1993 a 2012 na população com menos de 20 anos da ALC usando informações comparáveis da base de dados do terceiro volume do estudo International Incidence of Childhood Cancer. Foram calculadas taxas de incidência específica por idade por milhão de pessoas-ano (ASR, na sigla em inglês) para subgrupos populacionais e taxas padronizadas por idade usando a população padrão mundial (WSR, na sigla em inglês). Resultados. No total, foram incluídos 36 744 casos únicos. No período de 2001 a 2010, a WSR para todos os tumores combinados na faixa etária de 0 a 14 anos foi de 132,6. Os diagnósticos mais frequentes foram leucemia (WSR de 48,7), neoplasias do sistema nervoso central (WSR de 23,0) e linfoma (WSR de 16,6). A ASR para todos os tumores combinados na faixa etária de 15 a 19 anos foi de 152,3, e a maior taxa foi a de linfoma (ASR de 30,2). A incidência foi maior no sexo masculino do que no sexo feminino e maior na América do Sul do que na América Central e no Caribe. De modo geral, em comparação com as estimativas mundiais, a incidência na ALC foi menor, exceto para leucemia e linfoma entre 0 e 14 anos e para outros tumores e tumores não especificados em qualquer idade. A taxa de incidência na faixa etária de 0 a 19 anos aumentou em 1,0% ao ano (IC de 95% [0,6, 1,3]) entre 1993 e 2012. Os registros incluídos cobriam 16% da população de 0 a 14 anos e 10% da população de 15 a 19 anos. Conclusões. Os padrões observados servem de referência para avaliar o status e a evolução da ocorrência de câncer infantil na região. É necessário garantir um apoio ampliado e consistente aos registros de câncer para aprimorar a representatividade e a disponibilidade das informações em tempo adequado para o controle do câncer infantil na ALC.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

[Facing fever in the pediatric patient: Checklist as a tool for parents]. / Checklist como herramienta para los padres ante la fiebre en el paciente pediátrico.

INTRODUCTION: In Western Europe, 20%-40% of children with fever request health care. Most of them present trivial viral infections, however, it is essential in pediatrics to distinguish patients who present a severe infection. This process begins with the recognition of the seriousness and the subsequent search for medical attention by the parents. METHODOLOGY: Analytical and cross-sectional observational study. One hundred patients were selected in two health centers. Sociodemographic data were collected, together with the responses to a checklist containing the signs and symptoms to request health care in case of fever. Subsequently, the checklist was filled out by the pediatrician. RESULTS: The mean age of the patients was 5.41 years. 50% consulted in the first 48h of fever evolution. In 42%, the response to all the items on the checklist was exactly the same between the companion and the pediatrician. There were no significant differences according to variables: first episode of fever (P=.262), age of the patient (P=.859), having a sibling (P=.880), family relationship of the companion (P=.648) or educational level of the companion (P=.828). CONCLUSIONS: Medical consultations for fever in pediatrics are carried out very early. A high percentage do not present alarm signs when they consult. There is a need to expand training on the alarm signs of fever in all parents, regardless of the number of children, age or educational level. The checklist as a tool for home assessment of fever has received high marks for its usefulness.

Cost analysis of next-generation imaging in high-risk prostate cancer staging.

INTRODUCTION AND OBJECTIVE: Next-generation imaging (NGI) tests, such as choline PET/CT and PSMA PET, have shown to increase sensitivity in the detection of nodal and metastatic disease in prostate cancer. However, their use implies an increase in diagnostic costs compared to conventional imaging (CI) tests such as CT and bone scan. The aim of our study was to determine which diagnostic pathway is more cost-effective in high-risk prostate cancer. MATERIAL AND METHOD: Cost-effectiveness analysis of the available imaging tests (CI, Choline/PSMA PET) for the staging of high-risk prostate cancer. Sensitivity and specificity were estimated based on published evidence, and costs were collected from the Management Department. In order to carry out a cost-effectiveness analysis, five diagnostic pathways were proposed estimating the accurate diagnoses. RESULTS: PSMA PET was the most accurate diagnostic option. The CI diagnostic workup was the most economical and CI+PSMA the most expensive. Analyzing the diagnostic cost-effectiveness ratio, CI+PSMA proved to be the most expensive (€5627.30 per correct diagnosis) followed by PET PSMA (€4987.11), choline (€4599.84) and CI (€4444.22). CONCLUSIONS: PSMA PET is the most accurate strategy in staging distant disease in patients with high-risk prostate cancer. Radiotracer uptake tests such as CI have been shown to be the most cost-effective option, followed by choline and PSMA.

Triple neurectomía transperitoneal laparoscópica y con asistencia robótica para el tratamiento del dolor inguinal crónico: descripción de la técnica, nuestra experiencia y resultados preliminares / Robot-assisted laparoscopic triple neurectomy for chronic inguinal pain: Description of the technique, our experience and preliminary results

Introducción. El dolor inguinal crónico o inguinodinia posthernioplastia es una complicación relativamente común y que puede llegar a ser muy incapacitante. El tratamiento quirúrgico mediante triple neurectomía es una opción terapéutica ante el fracaso de tratamientos previos (terapia oral, local o neuromodulación).ObjetivoDescripción retrospectiva de la técnica quirúrgica y resultados de la triple neurectomía laparoscópica y con asistencia robótica en el tratamiento de la inguinodinia crónica.Material y métodosSe describen los criterios de inclusión/exclusión, así como la técnica quirúrgica empleada en 7 pacientes intervenidos en el Complejo Asistencial Universitario de León (Servicio de Urología) tras no responder a otras alternativas terapéuticas.ResultadosLos pacientes presentaban dolor crónico inguinal reportando una valoración en la escala EVA del dolor prequirúrgica de 7,43 sobre 10. Tras la cirugía, dicha valoración se redujo a 3,71 al primer día postoperatorio y a 4,2 puntos al año de la intervención. El alta hospitalaria se produjo a las 24h de la cirugía y no se reportaron complicaciones relevantes.ConclusionesLa triple neurectomía laparoscópica o con asistencia robótica es una técnica segura, reproducible y eficaz en el tratamiento del dolor inguinal crónico refractario a otros tratamientos. (AU)

Introduction. Chronic inguinal pain or inguinodynia following hernioplasty is a relatively common complication that can be very incapacitating. Surgical treatment by triple neurectomy is a therapeutic option when previous treatments (oral/local therapy or neuromodulation) have failed.ObjectiveRetrospective description of the surgical technique and results of laparoscopic and robot-assisted triple neurectomy for chronic inguinodynia.Material and methodsWe describe the inclusion/exclusion criteria as well as the surgical technique applied in 7 patients operated on at the University Health Care Complex of León (Urology Department) after failure of other treatment options.ResultsThe patients presented chronic groin pain, reporting a preoperative pain VAS of 7.43 out of 10. After surgery, this score was reduced to 3.71 on the first postoperative day and to 4.2 points one year after surgery. Hospital discharge occurred 24hours after surgery with no relevant complications being reported.ConclusionsLaparoscopic or robot-assisted triple neurectomy is a safe, reproducible, and effective technique for the treatment of chronic groin pain refractory to other treatments. (AU)

Genomic characterization and transcription analysis of European sea bass (Dicentrarchus labrax) rtp3 genes.

Fish RTP3, belonging to the receptor-transporting protein family, display several functions, including a putative antiviral role as virus-responsive gene. In this work, we have identified and characterized two different European sea bass rtp3 genes. In addition, an in vivo transcription analysis in response to LPS, poly I:C and betanodavirus infection (RGNNV genotype) has been performed. The sequence analysis showed that European sea bass displays two rtp3 genes, X1 and X2, composed of two exons and a single intron (1007-bp and 888-bp long, respectively), located within the ORF sequence. The full-length cDNA is 1969 bp for rtp3 X1, and 1491 bp for rtp3 X2. Several ATTTA motifs have been found in the intron sequence of both genes, whereas rtp3 X1 also contains this motif in both untranslated regions. The transcription analyses revealed significant level of rtp3 X2 mRNA in brain and head kidney after LPS and poly I:C inoculation; however, the induction elicited by RGNNV infection was much higher, suggesting an essential role for this protein in controlling NNV infections.

EXO1-mediated DNA repair by single-strand annealing is essential for BRCA1-deficient cells.

Deficiency for the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) leads to chromosomal instability and diseases such as cancer. Yet, defective HR also results in vulnerabilities that can be exploited for targeted therapy. Here, we identify such a vulnerability and show that BRCA1-deficient cells are dependent on the long-range end-resection factor EXO1 for survival. EXO1 loss results in DNA replication-induced lesions decorated by poly(ADP-ribose)-chains. In cells that lack both BRCA1 and EXO1, this is accompanied by unresolved DSBs due to impaired single-strand annealing (SSA), a DSB repair process that requires the activity of both proteins. In contrast, BRCA2-deficient cells have increased SSA, also in the absence of EXO1, and hence are not dependent on EXO1 for survival. In agreement with our mechanistic data, BRCA1-mutated tumours have elevated EXO1 expression and contain more genomic signatures of SSA compared to BRCA1-proficient tumours. Collectively, our data indicate that EXO1 is a promising novel target for treatment of BRCA1-deficient tumours.

Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1. Associations were also observed for LZTR1, ATR and BARD1 with P < 1 × 10-4. Associations between predicted deleterious rare missense or protein-truncating variants and breast cancer were additionally identified for CDKN2A at exome-wide significance. The overall contribution of coding variants in genes beyond the previously known genes is estimated to be small.

Burden in caregivers of primary care patients with dementia: influence of neuropsychiatric symptoms according to disease stage (NeDEM project).

BACKGROUND: Caregiver burden is related to personal factors and patient characteristics and is greater when neuropsychiatric symptoms (NPSs) are present. OBJECTIVE: Estimate the prevalence of burden among caregivers of dementia patients and its association with NPSs and identify NPSs causing greater caregiver distress according to dementia stage. METHODS: A cross-sectional observational study in caregivers of noninstitutionalized dementia patients was conducted. Caregiver variables were sociodemographic, time of care, NPS-associated distress based on the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D) and burden based on the Zarit Burden Interview (ZBI). Patient variables were time since disease onset, Global Deterioration Scale (GDS) disease stage, functional assessment and NPS presence and intensity according to the Neuropsychiatric Inventory (NPI). The mean ZBI score, prevalence of burden and NPI-D score with 95% CIs at each dementia stage were estimated. Factors associated with burden were identified by multivariate analysis. RESULTS: Of the 125 caregivers included, 77.6% were women, with a mean age of 60.7 (± 14.3) years; 78.4% (95%CI: 71.0; 86.0) experienced burden. The mean ZBI score was 12.3 (95%CI: 11.6; 12.9) and increased according to NPS number (p = 0.042). The NPSs causing the most burden were disinhibition (93.5%), irritability (87.3%) and agitation (86.1%). Agitation, apathy, and sleep disorders were the NPSs generating the greatest overall caregiver distress; depression (max NPI-D 1.9), hyperactivity (max NPI-D 2.1), and psychosis symptoms (max NPI-D 1.6) generated the greatest distress at stage GDS 3, stages GDS 4-5, and stages GDS 6-7, respectively. The NPI score (OR = 1.0, 95%CI 1.0; 1.1), intensity of irritability (OR = 1.2, 95%CI 1.0; 1.6), disinhibition (OR = 2.6, 95%CI 1.1; 5.8) and hyperactivity subsyndrome (OR = 1.1, 95%CI 1.0; 1.2) were associated with caregiver burden. Other associated factors were female gender (OR = 6.0, 95%CI 1.6; 22.8), ≥ 8 h daily care (OR = 5.6, 95%CI 1.4; 22.8), working outside the home (OR = 7.6, 95%CI 1.8; 31.8), living with the patient (OR = 4.5, 95%CI 1.1; 19.6), kinship (OR = 5.4, 95%CI 1.0; 28.2) and lower patient education (OR = 8.3, 95%CI 2.3; 30.3). CONCLUSIONS: The burden on caregivers of dementia patients is high and associated with NPS presence and intensity. Disinhibition and irritability caused the highest burden. Depression, hyperactivity and psychosis produce more distress in mild, mild-moderate and severe dementia, respectively.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

The genetic variability and evolution of red-spotted grouper nervous necrosis virus quasispecies can be associated with its virulence.

Nervous necrosis virus, NNV, is a neurotropic virus that causes viral nervous necrosis disease in a wide range of fish species, including European sea bass (Dicentrarchus labrax). NNV has a bisegmented (+) ssRNA genome consisting of RNA1, which encodes the RNA polymerase, and RNA2, encoding the capsid protein. The most prevalent NNV species in sea bass is red-spotted grouper nervous necrosis virus (RGNNV), causing high mortality in larvae and juveniles. Reverse genetics studies have associated amino acid 270 of the RGNNV capsid protein with RGNNV virulence in sea bass. NNV infection generates quasispecies and reassortants able to adapt to various selective pressures, such as host immune response or switching between host species. To better understand the variability of RGNNV populations and their association with RGNNV virulence, sea bass specimens were infected with two RGNNV recombinant viruses, a wild-type, rDl956, highly virulent to sea bass, and a single-mutant virus, Mut270Dl965, less virulent to this host. Both viral genome segments were quantified in brain by RT-qPCR, and genetic variability of whole-genome quasispecies was studied by Next Generation Sequencing (NGS). Copies of RNA1 and RNA2 in brains of fish infected with the low virulent virus were 1,000-fold lower than those in brains of fish infected with the virulent virus. In addition, differences between the two experimental groups in the Ts/Tv ratio, recombination frequency and genetic heterogeneity of the mutant spectra in the RNA2 segment were found. These results show that the entire quasispecies of a bisegmented RNA virus changes as a consequence of a single point mutation in the consensus sequence of one of its segments. Sea bream (Sparus aurata) is an asymptomatic carrier for RGNNV, thus rDl965 is considered a low-virulence isolate in this species. To assess whether the quasispecies characteristics of rDl965 were conserved in another host showing different susceptibility, juvenile sea bream were infected with rDl965 and analyzed as above described. Interestingly, both viral load and genetic variability of rDl965 in seabream were similar to those of Mut270Dl965 in sea bass. This result suggests that the genetic variability and evolution of RGNNV mutant spectra may be associated with its virulence.

Efficacy of Protein Baits with Fipronil to Control Vespa velutina nigrithorax (Lepeletier, 1836) in Apiaries.

The yellow-legged hornet (Vespa velutina nigrithorax), outside its natural range, has become a major threat to domestic bees. Several control methods have been used to fight against V. velutina, but the results achieved are not satisfactory. The use of protein baits with biocides has shown to be an effective method to control invasive wasp populations, but they have not been used to control V. velutina. Thus, the efficacy of protein baits containing fipronil to reduce the presence of hornets in apiaries was evaluated in this study. After laboratory determination of the optimal efficacy of a protein bait at a 0.01% concentration of fipronil, field trials were conducted involving 222 beekeepers. The data reported by the 90 beekeepers who completed the requested questionnaire demonstrated that in the groups of apiaries with the highest pressure of hornets (groups with 10-30 and >30 hornets), there was a significant decrease in the presence of V. velutina, lasting at least two weeks. The reduction in the number of hornets was positively correlated with bait consumption, and bait consumption was positively correlated with the number of hornets present at the time of treatment. Although the method used has shown good efficacy and the concentration of fipronil used was very low; possible negative effects on the environment should also be evaluated.