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Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.
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Dieta Alta en Grasa , Epigénesis Genética , Mitocondrias , ARN Mitocondrial , Espermatozoides , Animales , Femenino , Humanos , Masculino , Ratones , Índice de Masa Corporal , Dieta Alta en Grasa/efectos adversos , Embrión de Mamíferos/citología , Embrión de Mamíferos/embriología , Embrión de Mamíferos/metabolismo , Epidídimo/citología , Epigénesis Genética/genética , Fertilización/genética , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Ratones Endogámicos C57BL , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Obesidad/genética , Obesidad/metabolismo , Obesidad/etiología , Oocitos/metabolismo , Sobrepeso/genética , Sobrepeso/metabolismo , Herencia Paterna/genética , ARN Mitocondrial/genética , ARN Mitocondrial/metabolismo , ARN Pequeño no Traducido/genética , ARN Pequeño no Traducido/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Espermatozoides/metabolismo , Testículo/citología , Transcripción GenéticaRESUMEN
BACKGROUND: Type 2 diabetes is an increasing health problem worldwide. HIIT has been proposed as an exercise alternative to be part of integral type 2 diabetes treatment. OBJECTIVE: The aim of this meta-analysis was to determine the effect of different types of chronic HIIT on glycaemic control, aerobic resistance, and body composition in individuals above 18 years with T2D. DESIGN: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered with PROSPERO on November 21st, 2021. DATA SOURCES: A systematic literature search of the following databases: EbscoHost (Academic Search Ultimate, Fuente Académica Plus, MEDline and SportDiscus), Web of Science, PubMed, and EMBASE between April of 2021 and April of 2023 was conducted. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligibility criteria included (1) participants aged ≥ 18 years with a diagnosis of type 2 diabetes, (2) an HIIT protocol with detailed description, (3) control group and/or continuous aerobic training comparison group, (4) report of pre-test and post-test values for at least one of the studied variables (from glycaemic control, aerobic resistance, and/or body composition), and (5) experimental or quasi-experimental intervention design. ANALYSES: Meta-analysis was made by a pre-post-test between-group analysis following the inverse variance heterogeneity model for each variable, and then, a subgroup analysis by type of HIIT was conducted. RESULTS: Of the 2817 records obtained, 180 records were included for meta-analysis. Significant improvements were found in the most part of the variables when HIIT was compared to control group, while fat-free mass kept without changes. HIIT vs. continuous aerobic training results showed and advantage in favor of HIIT for fasting blood glycemia. Subgroup analysis refers a possible advantage of SI-HIIT and SIT-HIIT in the improvement of fasting glycemia and SIT-HIIT advantage in HOMA 1-IR decrease. CONCLUSIONS: HIIT improves glycaemic control, aerobic resistance, and % fat and waist circumference, and kept fat-free mass unchanged in individuals with T2D. SI-HIIT and SIT-HIIT could be better than the other types of HIIT. HIIT benefit is similar to continuous aerobic training except for fasting blood glycemia.
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Diabetes Mellitus Tipo 2 , Entrenamiento de Intervalos de Alta Intensidad , Humanos , Entrenamiento de Intervalos de Alta Intensidad/métodos , Diabetes Mellitus Tipo 2/terapia , Control Glucémico , Composición Corporal , Ejercicio FísicoRESUMEN
Due to the high intensity and MHz repetition rate of photon pulses generated by the European X-ray Free-Electron Laser, the heat load on silicon crystal monochromators can become large and prevent ideal transmission in Bragg diffraction geometry due to crystal deformation. Here, we present experimental data illustrating how heat load affects the performance of a cryogenically cooled monochromator under such conditions. The measurements are in good agreement with a depth-uniform model of X-ray dynamical diffraction taking beam absorption and heat deformation of the crystals into account.
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The Materials Imaging and Dynamics (MID) instrument at the European X-ray Free-Electron Laser (EuXFEL) facility is described. EuXFEL is the first hard X-ray free-electron laser operating in the MHz repetition range which provides novel science opportunities. The aim of MID is to enable studies of nano-structured materials, liquids, and soft- and hard-condensed matter using the bright X-ray beams generated by EuXFEL. Particular emphasis is on studies of structure and dynamics in materials by coherent scattering and imaging using hard X-rays. Commission of MID started at the end of 2018 and first experiments were performed in 2019.
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Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16 - 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.
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PURPOSE: Stand-alone zero-profile devices have already proven safety, and a reduced dysphagia rate was assumed. So far, no level-one evidence is available to prove the proposed advantages of zero-profile implants in multilevel procedures. The aim of this RCT was to compare the clinical and radiological outcome of a zero-profile spacer versus cage + plate in two-level ACDF. METHODS: Consecutive patients with contiguous two-level cDD were randomly assigned either to the interventional group (zero-profile device) or to the control group (cage + plate). Primary endpoint of the study was the prevalence of dysphagia at 24 months. Disability, progress of adjacent segment degeneration, fusion status and loss of correction were analyzed as secondary outcome measure. Primary outcome parameter was statistically analyzed by Chi-square test. RESULTS: Forty-one patients met inclusion criteria and were randomly assigned to the interventional and the control group. Dysphagia was frequent in either group at 3 months FU favoring interventional group (p = 0.078). At final FU, less patients of the interventional group complained about dysphagia, but the difference was not significant. No relevant differences at final FU were recorded for NPDI, loss of correction and adjacent-level degeneration. Fusion rate was slightly lower in the interventional group. DISCUSSION: Two-level ACDF either by a stand-alone zero-profile spacer or cage + plate is safe. Using a zero-profile cage dysphagia was infrequent at 24 months, but the value did not reach statistical significance in comparison with the cage + plate. Hence, this randomized trial was not able to prove the proposed clinical superiority for dysphagia rates for zero-profile anchored spacer in two-level cDD.
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Discectomía , Fusión Vertebral , Placas Óseas , Vértebras Cervicales/cirugía , Humanos , Complicaciones Posoperatorias , Estudios Prospectivos , Fusión Vertebral/efectos adversos , Resultado del TratamientoRESUMEN
Nowadays, although minimally invasive procedures are the standard for the treatment of thoracolumbar spinal injuries, these techniques are not yet established for the cervical spine. This is due to anatomical and technical reasons and also due to the fact that the classical anterior decompression and fusion procedure already fulfils the criteria of minimally invasiveness and is suitable for the vast majority of injuries. The existing literature consists mainly of case reports and small comparative cohort studies, the results of which are presented. There is a minimally invasive variant for nearly all open procedures, mainly in the upper cervical spine but also in the lower cervical spine. The further development of these promising techniques is still pending.
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Procedimientos Quirúrgicos Mínimamente Invasivos , Fusión Vertebral , Traumatismos Vertebrales , Procedimientos Quirúrgicos de Citorreducción , Humanos , Vértebras Lumbares , Vértebras TorácicasRESUMEN
This study focuses on drivers for changing urban flood risk. We suggest a framework for guiding climate change adaptation action concerning flood risk and manageability in cities. The identified key drivers of changing flood hazard and vulnerability are used to provide an overview of each driver's impact on flood risk and manageability at the city level. We find that identified drivers for urban flood risk can be grouped in three different priority areas with different time horizon. The first group has high impact but is manageable at city level. Typical drivers in this group are related to the physical environment such as decreasing permeability and unresponsive engineering. The second group of drivers is represented by public awareness and individual willingness to participate and urbanization and urban sprawl. These drivers may be important and are manageable for the cities and they involve both short-term and long-term measures. The third group of drivers is related to policy and long-term changes. This group is represented by economic growth and increasing values at risk, climate change, and increasing complexity of society. They have all high impact but low manageability. Managing these drivers needs to be done in a longer time perspective, e.g., by developing long-term policies and exchange of ideas.
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Cambio Climático , Inundaciones , Ciudades , Ambiente , UrbanizaciónRESUMEN
Muscle fiber cross-sectional area (CSA) and proportion of different fiber types are important determinants of muscle function and overall metabolism. Genetic variation plays a substantial role in phenotypic variation of these traits; however, the underlying genes remain poorly understood. This study aimed to map quantitative trait loci (QTL) affecting differences in soleus muscle fiber traits between the LG/J and SM/J mouse strains. Fiber number, CSA, and proportion of oxidative type I fibers were assessed in the soleus of 334 genotyped female and male mice of the F34 generation of advanced intercross lines (AIL) derived from the LG/J and SM/J strains. To increase the QTL detection power, these data were combined with 94 soleus samples from the F2 intercross of the same strains. Transcriptome of the soleus muscle of LG/J and SM/J females was analyzed by microarray. Genome-wide association analysis mapped four QTL (genome-wide P < 0.05) affecting the properties of muscle fibers to chromosome 2, 3, 4, and 11. A 1.5-LOD QTL support interval ranged between 2.36 and 4.67 Mb. On the basis of the genomic sequence information and functional and transcriptome data, we identified candidate genes for each of these QTL. The combination of analyses in F2 and F34 AIL populations with transcriptome and genomic sequence data in the parental strains is an effective strategy for refining QTL and nomination of the candidate genes.
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Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Mapeo Físico de Cromosoma , Animales , Cromosomas de los Mamíferos/genética , Cruzamientos Genéticos , Femenino , Regulación de la Expresión Génica , Estudios de Asociación Genética , Genómica , Masculino , Ratones , Fenotipo , Sitios de Carácter Cuantitativo/genética , Caracteres SexualesRESUMEN
BACKGROUND: To examine the relation of carcinoembryonic antigen (CEA) response with tumor response and survival in patients with (K)RAS wild-type metastatic colorectal cancer receiving first-line chemotherapy in the FIRE-3 trial comparing FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab. PATIENTS AND METHODS: CEA response assessed as the percentage of CEA decrease from baseline to nadir was evaluated for its association with tumor response and survival. Receiver operating characteristic analysis revealed an optimal cut-off value of 75% using the maximum of sensitivity and specificity for CEA response to discriminate CEA responders from non-responders. In addition, the time to CEA nadir was calculated. RESULTS: Of 592 patients in the intent-to-treat population, 472 were eligible for analysis of CEA (cetuximab arm: 230 and bevacizumab arm: 242). Maximal relative CEA decrease (%) significantly (P = 0.003) differed between the cetuximab arm (median 83.0%; IQR 40.9%-94.7%) and the bevacizumab arm (median 72.3%; IQR 26.3%-91.0%). In a longitudinal analysis, the CEA decrease occurred faster in the cetuximab arm and was greater than in the bevacizumab arm at all evaluated time points until 56 weeks after treatment start. CEA nadir occurred after 3.3 months (cetuximab arm) and 3.5 months (bevacizumab arm), (P = 0.49). In the cetuximab arm, CEA responders showed a significantly longer progression-free survival [11.8 versus 7.4 months; hazard ratio (HR) 1.53; 95% Cl, 1.15-2.04; P = 0.004] and longer overall survival (36.6 versus 21.3 months; HR 1.73; 95% Cl, 1.24-2.43; P = 0.001) than CEA non-responders. Analysis of extended RAS wild-type patients revealed similar results. CONCLUSION: In the FIRE-3 trial, CEA decrease was significantly faster and greater in the cetuximab arm than in the bevacizumab arm and correlated with the prolonged survival observed in patients receiving FOLFIRI plus cetuximab. CLINICAL TRIALS NUMBER: NCT00433927 (ClinicalTrials.gov); AIO KRK0306 FIRE-3.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Camptotecina/análogos & derivados , Antígeno Carcinoembrionario/genética , Cetuximab/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Cetuximab/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Exones/genética , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
BACKGROUND/OBJECTIVES: Irisin has been suggested as a novel myokine with beneficial effects in rodents. However, previous data in humans showed conflicting results regarding its association with metabolic phenotypes and regulation of secretion. Furthermore, although an association of rs726344 in FNDC5 (fibronectin type III domain containing 5) coding for irisin with insulin sensitivity was reported, the effects of genetic variation at this locus on irisin serum levels have not been investigated, so far. Therefore, we investigated circulating irisin and the associations with rs726344 in a cohort of >1000 subjects. SUBJECTS/METHODS: Irisin serum concentrations were measured with enzyme-linked immunosorbent assay. Associations with metabolic parameters including renal function, glucose and lipid metabolism, inflammation, as well as adipokine profiles, were assessed in regression models. Dynamic changes of serum irisin were investigated during oral glucose tolerance test (OGTT) in a subset of the cohort (n=136). rs726344 was genotyped in all subjects and analyzed for associations with serum irisin and traits of the metabolic syndrome. RESULTS: Irisin was negatively associated with fat mass, fasting glucose and dyslipidemia but not with other adipokines. Moreover, irisin decreased during an OGTT in a subcohort comprising subjects with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. rs726344 was not associated with serum irisin levels or with other anthropometric and biochemical parameters. CONCLUSIONS: Circulating irisin levels are associated with a beneficial metabolic profile but not with other adipokines and not with rs726344 in our cohort. Our data suggest a potential favorable role of irisin in the regulation of metabolism.
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Glucemia/metabolismo , Fibronectinas/sangre , Predisposición Genética a la Enfermedad/epidemiología , Resistencia a la Insulina/genética , Síndrome Metabólico/sangre , Adulto , Distribución de la Grasa Corporal , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibronectinas/genética , Regulación de la Expresión Génica/genética , Frecuencia de los Genes , Alemania/epidemiología , Humanos , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Cadmium-enrichment of farmland soil greatly threatens the sustainable use of soil resources and the safe cultivation of grain. This review paper briefly introduces the status of farmland soil as well as grain, which are both often polluted by cadmium (Cd) in China, and illustrates the major sources of Cd contaminants in farmland soil. In order to meet soil environmental quality standards and farmland environmental quality evaluation standards for edible agricultural products, Cd-enriched farmland soil is frequently remediated with the following prevailing techniques: dig and fill, electro-kinetic remediation, chemical elution, stabilisation and solidification, phytoremediation, field management and combined remediation. Most remediation techniques are still at the stage of small-scale trial experiments in China and few techniques are assessed in field trials. After comparing the technical and economical applicability among different Cd-enriched farmland soil remediation techniques, a novel ecological and hydraulic remediation technique has been proposed, which integrated the advantages of chemical elution, solidification and stabilisation, phytoremediation and field management. The ecological and hydraulic remediation concept is based on existing irrigation and drainage facilities, ecological ditches (ponds) and agronomic measures, which mainly detoxify the Cd-enriched soil during the interim period of crop cultivation, and guarantee the grain safety during its growth period. This technique may shift the challenge from soil to water treatment, and thus greatly enhances the remediation efficiency and shortens the remediation duration. Moreover, the proposed ecological and hydraulic remediation method matches well with the practical choice of cultivation while remediation for Cd-enriched soil in China, which has negligible impacts on the normal crop cultivation process, and thus shows great potential for large area applications.
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Agricultura , Biodegradación Ambiental , Cadmio/análisis , Contaminantes del Suelo/análisis , China , HumanosRESUMEN
BACKGROUND: Microsurgical preparation is limited by geometric and mechanical constraints. In preparation for clinical use, this study investigates performance, ease of handling and precision of a novel manipulator concept for microsurgery. MATERIAL AND METHODS: A group of 15 ENT experienced doctors, as well as a group of 17 medical students with low/non surgical experience participated in the study. Each of the subjects carried out 4 trials of simulated surgeries on a phantom with built-in force sensors. The task was to apply a defined force between 1.5 and 2 N using a Fisch micro perforator, 16 cm length, 0.4 mm (Storz) targeting holes with a diameter of 0.5 mm. For comparison, the Fisch micro perforator was moved manually or with the manipulator. RESULTS: Assessing the total number of errors proved a significantly lower error number (p<0.0001) and an improvement of the accuracy of 76% with the manipulator. The time requirement for the procedure with the micro manipulator is on average 2-3 times higher than with manual control (p<0.0001). But it is notable that this time requirement significantly decreases with training (p<0.0001). CONCLUSION: The study shows a significant reduction in the number of errors by using a new manipulator concept compared to the non-augmented human hand in an experimental setup. We observed a significant learning effect when subjects applied the micro manipulator, resulting in reduction of the time requirement while maintaining a constant number of errors.
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Oído Medio/cirugía , Micromanipulación/instrumentación , Modelos Anatómicos , Prótesis Osicular , Otitis Media/cirugía , Otosclerosis/cirugía , Procedimientos Quirúrgicos Robotizados/instrumentación , Cirugía del Estribo/instrumentación , Cirugía Asistida por Computador/instrumentación , Adulto , Femenino , Humanos , Curva de Aprendizaje , Masculino , Errores Médicos/prevención & control , Tempo Operativo , Otolaringología/educación , Estudiantes de Medicina , Equipo Quirúrgico , Telemedicina/instrumentaciónRESUMEN
Higher levels of fibrinogen or cholesterol were associated with improved hearing recovery in SSHL patients after treatment with HELP-apheresis (Heparin-induced extracorporeal LDL precipitation apheresis). The present trial was performed to demonstrate HELP-related effects on relevant metabolic and inflammatory parameters in the context of SSHL treatment. In the framework of a single arm non-controlled trial, we investigated the variation of metabolic and inflammatory parameters using HELP-apheresis for a defined group of 100 patients with SSHL. Based on cut off inclusion criteria (Serum LDL-cholesterol >1.6 g/l and/or fibrinogen >2.0 g/l, SSHL in minimum three frequencies more than 30 dB, time after event not longer than 6 days), the protocol followed a strict time line with one single shot HELP-apheresis and follow-up monitoring including laboratory parameters at six defined time points. If HELP-apheresis could not effect improvement of hearing on day 5, additional corticosteroid treatment was applied. Concentration of anti-inflammatory IL-10 increased while other proinflammatory parameters declined. Serum levels of all measured sterols and apolipoproteins decreased significantly. None of the investigated parameters were suitable to predict hearing improvement of the patients. Levels of fibrinogen and LDL-cholesterol were not prognostic for outcome after HELP-apheresis. A significant (p < 0.001) increase of anti-inflammatory IL-10 after apheresis was notable, while most of the proinflammatory parameters declined. Despite the limited validity of a single arm non-controlled trial, these alterations on immune modulating factors indicate possible secondary pleiotropic effects caused by HELP-apheresis.
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Eliminación de Componentes Sanguíneos/métodos , Fibrinógeno/análisis , Pérdida Auditiva Sensorineural/terapia , Pérdida Auditiva Súbita/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , LDL-Colesterol/sangre , Circulación Extracorporea , Femenino , Heparina/uso terapéutico , Humanos , Interleucina-10/sangre , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
Based on level I evidence, postoperative platinum-based radiochemotherapy (PORCT) is the recommended standard of care in defined risk situations after resection of squamous cell carcinomas of the larynx and hypopharynx (LHSCC). The value of the addition of chemotherapy to adjuvant radiation in intermediate and high risk situations other than extracapsular spread or R1-/R2 resection is still debated. From 1993 to 2009, 555 patients (median follow-up: 24.4 months) with advanced LHSCC (UICC stages III-IVB) were treated in a curative intent. Patient data were continuously documented in the county of Leipzig cancer registry and were retrospectively analyzed as mono institutional survey. PORCT was introduced into the standard procedures in 2004, but also applied before in selected cases. Based on this paradigm shift, the patient population was divided into two comparative groups treated before and after 2004. 361 patients were treated before 2004. 43.8 % received primary surgery (OP) + postoperative radiotherapy (PORT) and 20.2 % OP + PORCT. 194 patients were treated after 2004: 21.1 % received OP + PORT and 35.6 % OP + PORCT. Regarding the PORCT groups, 20.6 % received cisplatin plus 5FU before 2004 which shifted to 59.4 % after 2004. The 3-year tumor-specific-survival rate of the whole cohort was improved from 47 to 60 % (p = 0.006). The subgroup treated with OP + PORT or PORCT improved from 56.1 to 68.5 % (p = 0.028). Localization proved to be a significant and independent factor. Only patients with advanced laryngeal cancer had significant improved survival (p < 0.01), while the improvement for hypopharyngeal cancer patients was not significant (p < 0.2). After 2004, there was a slight increase (+10.2 %) of primary radiochemotherapy (pRCT) due to stronger selection if R0 > 5 mm-resectability is unlikely. Standardised use of PORCT and pRCT considering clear indications showed to be significantly involved in improved survival in advanced LHSCC.
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Carcinoma de Células Escamosas , Quimioterapia Adyuvante/métodos , Neoplasias de Cabeza y Cuello , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Radioterapia/métodos , Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Cisplatino/administración & dosificación , Terapia Combinada/métodos , Estudios de Seguimiento , Alemania , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Humanos , Neoplasias Hipofaríngeas/patología , Neoplasias Hipofaríngeas/terapia , Hipofaringe/patología , Hipofaringe/cirugía , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Laringe/patología , Laringe/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de SupervivenciaRESUMEN
The aim was to compare the impact of different design (aggregate size) and operational (contact time, empty time and chemical oxygen demand (COD) loading) variables on the long-term and seasonal performance of vertical-flow constructed wetland filters operated in tidal flow mode before and after a one-off spill of diesel. Ten different vertical-flow wetland systems were planted with Phragmites australis (Cav.) Trin. ex Steud. (common reed). Approximately 130 g of diesel fuel was poured into four wetland filters. Before the spill, compliance with secondary wastewater treatment standards was achieved by all wetlands regarding ammonia-nitrogen (NH4-N), nitrate-nitrogen (NO3-N) and suspended solids (SS), and non-compliance was recorded for biochemical oxygen demand and ortho-phosphate-phosphorus (PO4-P). Higher COD inflow concentrations had a significantly positive impact on the treatment performance for COD, PO4-P and SS. The wetland with the largest aggregate size had the lowest mean NO3-N outflow concentration. However, the results were similar regardless of aggregate size and resting time for most variables. Clear seasonal outflow concentration trends were recorded for COD, NH4-N and NO3-N. No filter clogging was observed. The removal efficiencies dropped for those filters impacted by the diesel spill. The wetlands system shows a good performance regarding total petroleum hydrocarbon (TPH) removal.
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Filtración , Eliminación de Residuos Líquidos , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Humedales , Compuestos de Amonio/análisis , Gasolina/análisis , Nitratos/análisis , Contaminación por Petróleo/análisis , Fosfatos/análisis , Estaciones del Año , Aguas Residuales/análisisRESUMEN
BACKGROUND: Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1-3 positive lymph nodes (LNs) only. PATIENTS AND METHODS: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. RESULTS: Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥ 20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18-0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). CONCLUSION: EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1-3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT02115204.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Antígeno Ki-67/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Taxoides/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Ammonia is exclusively synthesized by the Haber-Bosch process starting from precious carbon resources such as coal or CH4. With H2O, H2 is produced and with N2, NH3 can be synthesized at high pressures and temperatures. Regrettably, the carbon is not incorporated into NH3 but emitted as CO2. Valuable carbon sources are consumed which could be used otherwise when carbon sources become scarce. We suggest an alternative process concept using an electrochemical membrane reactor (ecMR). A complete synthesis process with N2 production and downstream product separation is presented and evaluated in a multi-scale model to quantify its energy consumption. A new micro-scale ecMR model integrates mass, species, heat and energy balances with electrochemical conversions allowing further integration into a macro-scale process flow sheet. For the anodic oxidation reaction H2O was chosen as a ubiquitous H2 source. Nitrogen was obtained by air separation which combines with protons from H2O to give NH3 using a hypothetical catalyst recently suggested from DFT calculations. The energy demand of the whole electrochemical process is up to 20% lower than the Haber-Bosch process using coal as a H2 source. In the case of natural gas, the ecMR process is not competitive under today's energy and resource conditions. In future however, the electrochemical NH3 synthesis might be the technology-of-choice when coal is easily accessible over natural gas or limited carbon sources have to be used otherwise but for the synthesis of the carbon free product NH3.
RESUMEN
Upon repetition, certain stimuli induce reduced neural responses (i.e., repetition suppression), whereas others evoke stronger signals (i.e., repetition enhancement). It has been hypothesized that stimulus properties (e.g., visibility) determine the direction of the repetition effect. Here, we show that the very same stimuli can induce both repetition suppression and enhancement, whereby the only determining factor is the number of repetitions. Repeating the same, initially novel low-visible pictures of scenes for up to 5 times enhanced the blood oxygen level-dependent (BOLD) response in scene-selective areas, that is, the parahippocampal place area (PPA) and the transverse occipital sulcus (TOS), presumably reflecting the strengthening of the internal representation. Additional repetitions (6-9) resulted in progressively attenuated neural responses indicating a more efficient representation of the now familiar stimulus. Behaviorally, repetition led to increasingly faster responses and higher visibility ratings. Novel scenes induced the largest BOLD response in the PPA and also higher activity in yet another scene-selective region, the retrospenial cortex (RSC). We propose that 2 separable processes modulate activity in the PPA: one process optimizes the internal stimulus representation and involves TOS and the other differentiates between familiar and novel scenes and involves RSC.
Asunto(s)
Mapeo Encefálico , Encéfalo/fisiología , Reconocimiento en Psicología/fisiología , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Adulto JovenRESUMEN
The Rasch-based, computerized adaptive assessment procedure RehaCAT allows to assess the ICF-oriented dimensions "activities in daily living", "functionality upper extremities" and "functionality lower extremities" as well as "depression" economically and reliably in orthopaedic rehabilitation patients. This validation study aimed at analyzing the multivariate association of the RehaCAT dimensions with the commonly applied ODI, SF-12 and HADS-D assessment scales in a sample of rehabilitation patient suffering from musculoskeletal diseases (spine disease: 58,7%). By means of structural equation modeling high convergent and divergent validity of the RehaCAT dimensions could be proven in a sample of N=184 rehabilitation patients (71,2% inpatient and 28,8% outpatient). In the resulting model between 41% (functionality upper extremities) and 76% (activities in daily living) of the RehaCAT dimensions could be explained mainly by the theoretical assumed predictor constructs. Because of its psychometric foundation, economy and validity, the RehaCAT provides an optimal basis to assess central ICF-oriented constructs in orthopaedic rehabilitation.