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Escalating wildfire frequency and severity, exacerbated by shifting climate patterns, pose significant ecological and economic challenges. Prescribed burns, a common forest management tool, aim to mitigate wildfire risks and protect biodiversity. Nevertheless, understanding the impact of prescribed burns on soil and microbial communities in temperate mixed forests, considering temporal dynamics and slash fuel types, remains crucial. Our study, conducted at the University of Tennessee Forest Resources AgResearch and Education Center in Oak Ridge, TN, employed controlled burns across various treatments, and the findings indicate that low-intensity prescribed burns have none or minimal short-term effects on soil parameters but may alter soil nutrient concentrations, as evidenced by significant changes in porewater acetate, formate, and nitrate concentrations. These burns also induce shifts in microbial community structure and diversity, with Proteobacteria and Acidobacteria increasing significantly post-fire, possibly aiding soil recovery. In contrast, Verrucomicrobia showed a notable decrease over time, and other specific microbial taxa correlated with soil pH, porewater nitrate, ammonium, and phosphate concentrations. Our research contributes to understanding the intricate relationships between prescribed fire, soil dynamics, and microbial responses in temperate mixed forests in the Southern Appalachian Region, which is valuable for informed land management practices in the face of evolving environmental challenges.
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OBJECTIVE: The nociceptive withdrawal reflex (NWR) has been proposed to read-out central sensitization (CS). Replicating a published study, it was assessed if the NWR magnitude reflects sensitization by painful heat. Additionally, NWR response rates were compared for two stimulation, the sural nerve at the lateral malleolus (SU) and the medial plantar nerve on the foot sole (MP), and three recording sites, biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) muscles. METHODS: 16 subjects underwent one experiment with six blocks of eight transcutaneous electrical stimulations to elicit the NWR while surface electromyography was collected. Tonic heat was concurrently applied in the same dermatome. Temperatures rose from 32 °C in the first to 46 °C in the last block following the previously published protocol. RESULTS: Tonic heat did not influence NWR magnitude. The highest NWR response rate was obtained for MP-TA combination (79%). Regarding elicitation in all three muscles, SU stimulation outperformed MP (59% vs 57%). CONCLUSIONS: The replication failed. NWR magnitude as a CS proxy in healthy subjects needs continued investigation. With respect to response rates, MP-TA proved efficient, whereas SU stimulation seemed preferable for multiple muscle recordings. SIGNIFICANCE: Unclear methodological descriptions in the original study affected CS and NWR replication. The NWR magnitude changes induced by CS may closely depend on the different stimulation methods used.
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Nocicepción , Umbral del Dolor , Humanos , Umbral del Dolor/fisiología , Nocicepción/fisiología , Dimensión del Dolor/métodos , Sensibilización del Sistema Nervioso Central , Reflejo/fisiología , Electromiografía/métodos , Músculo Esquelético/fisiología , Estimulación EléctricaRESUMEN
A combination of direct current (DC) fields and high amplitude radio frequency (RF) fields is necessary to trap ions in a Paul trap. Such high electric RF fields are usually reached with the help of a resonator in close proximity to the ion trap. Ion trap based quantum computers profit from good vacuum conditions and low heating rates that cryogenic environments provide. However, an impedance matching network between the resonator and its RF source is necessary, as an unmatched resonator would require higher input power due to power reflection. The reflected power would not contribute to the RF trapping potential, and the losses in the cable induce additional heat into the system. The electrical properties of the matching network components change during cooling, and a cryogenic setup usually prohibits physical access to integrated components while the experiment is running. This circumstance leads to either several cooling cycles to improve the matching at cryogenic temperatures or the operation of poorly matched resonators. In this work, we demonstrate an RF resonator that is actively matched to the wave impedance of coaxial cables and the signal source. The active part of the matching circuit consists of a varactor diode array. Its capacitance depends on the DC voltage applied from outside the cryostat. We present measurements of the power reflection, the Q-factor, and higher harmonic signals resulting from the nonlinearity of the varactor diodes. The RF resonator is tested in a cryostat at room temperature and cryogenic temperatures, down to 4.3 K. A superior impedance matching for different ion traps can be achieved with this type of resonator.
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Cosmogenic radiosulfur (35S; half-life: 87.4 days) is transferred with the rain to the groundwater (as 35SO42-) and can be used as residence time tracer for the detection of sub-yearly groundwater residence times. Due to the distinct but non-regular annual 35S pattern in precipitation, related data evaluation requires consideration of a35S input function that is based on representative rain samples. While minor rain events can easily be sampled quantitatively and hence representatively, a long-lasting rain event may get documented by a sample that represents only a certain sequence of the event, thus potentially resulting in a35S activity concentration that might not be representative. With the aim to examine the magnitude of temporal variations of the 35S activity concentration in rain during long-lasting rain events, we present and discuss two related exemplary 35S time series. Furthermore, we evaluate the applicability of the parameters total sulfate and electrical conductivity (EC), both detected in rainwater as easily attainable 35S proxies. The results of the study show (i) that the 35S activity concentration may vary substantially during long-lasting rain events due to atmospheric migration processes and aerosol washout and (ii) that neither sulfate nor EC are suitable as 35S proxies due to the different origin of 35S on the one hand and sulfate/EC on the other. Hence, for the determination of a35S activity concentration that is representative for a long-lasting rain event 35S analyses of an adequate number of sub-samples cannot be avoided.
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Agua Subterránea , Monitoreo de Radiación , Aerosoles/análisis , Monitoreo del Ambiente , Lluvia , SulfatosRESUMEN
BACKGROUND AND PURPOSE: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.
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Médula Cervical/fisiopatología , Enfermedades de la Médula Espinal/fisiopatología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Movimiento (Física) , Enfermedades de la Médula Espinal/etiología , Estenosis Espinal/complicaciones , Estenosis Espinal/fisiopatologíaRESUMEN
Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.
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Síndromes de Neurotoxicidad , Receptores Quiméricos de Antígenos , Tratamiento Basado en Trasplante de Células y Tejidos , Humanos , Inmunoterapia Adoptiva , Recurrencia Local de Neoplasia , Receptores de Antígenos de Linfocitos T/genética , Receptores Quiméricos de Antígenos/genéticaRESUMEN
Perceptual learning, the ability to improve the sensitivity of sensory perception through training, has been shown to exist in all sensory systems but the vestibular system. A previous study found no improvement of passive self-motion thresholds in the dark after intense direction discrimination training of either yaw rotations (stimulating semicircular canals) or y-translation (stimulating otoliths). The goal of the present study was to investigate whether perceptual learning of self-motion in the dark would occur when there is a simultaneous otolith and semicircular canal input, as is the case with roll tilt motion stimuli. Blindfolded subjects (n = 10) trained on a direction discrimination task with 0.2-Hz roll tilt motion stimuli (9 h of training, 1,800 trials). Before and after training, motion thresholds were measured in the dark for the trained motion and for three transfer conditions. We found that roll tilt sensitivity in the 0.2-Hz roll tilt condition was increased (i.e., thresholds decreased) after training but not for controls who were not exposed to training. This is the first demonstration of perceptual learning of passive self-motion direction discrimination in the dark. The results have potential therapeutic relevance as 0.2-Hz roll thresholds have been associated with poor performance on a clinical balance test that has been linked to more than a fivefold increase in falls.
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Percepción de Movimiento , Humanos , Aprendizaje , Movimiento (Física) , Membrana Otolítica , Percepción VisualRESUMEN
Information about groundwater residence times is essential for evaluating appropriate groundwater abstraction rates and aquifer vulnerabilities and hence for sustainable groundwater management in general. Naturally occurring radionuclides are suitable tools for related investigations. While the applicability of several long-lived radionuclides for the investigation of long-term processes has been demonstrated frequently, residence times of less than one year are only scarcely discussed in the literature. That is due to the rather small number of applicable radionuclides that show adequately short half-lives. A promising approach for investigating sub-yearly residence times applies radioactive sulphur. 35S is continuously produced in the upper atmosphere from where it is transferred with the rain to the groundwater. As soon as the water enters the subsurface its 35S activity concentration decreases with an 87.4 day half-life. This makes 35S suitable for investigating sub-yearly groundwater residence times. However, the low 35S activities in natural waters require sulphate pre-concentration for 35S detection by means of liquid scintillation counting (LSC). That is usually done by sulphate extraction from large water samples with an anion-exchange resin (Amberlite IRA400, Cl-form), elution from the resin with NaCl, and precipitation as BaSO4. Our study aimed at optimizing the standard sample preparation procedure by avoiding the laborious precipitation step. We suggest (i) sulphate extraction using the exchange resin Amberlite IRA67 (OH-form), (ii) elution with ammonium hydroxide, (iii) evaporation of the eluate and (iv) dissolving the resulting dry precipitate in 2 ml H2O. In contrast to the standard approach our method results in a final sample solution of low ionic strength, which allows applying the water miscible scintillation cocktail Hionic-Fluor®. Since Hionic-Fluor accepts only aqueous solutions of low ionic strength the approach is applicable for waters with high 35S/32SO42- ratios, i.e., low total sulphate sample loads (e.g. rainwater).
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Agua Subterránea/química , Monitoreo de Radiación , Radioisótopos , Sulfatos , Contaminantes Radiactivos del AguaRESUMEN
STUDY DESIGN: Observational cohort study. OBJECTIVE: To benchmark all-cause and cause-specific mortality following NTSCI to the general population (GP). SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) Medical Record study were probabilistically linked with cause of death (CoD) information from the Swiss National Cohort. Standardized mortality ratios (SMRs) were estimated for all-cause and cause-specific mortality. Competing risk frameworks were used to estimate the probability of death due to specific CoD. RESULTS: One thousand five hundred and one individuals were admitted for first rehabilitation with NTSCI between 1990-2011; CoD information was available for 454 individuals of the 525 individuals that died. Overall, the mortality rate for persons with NTSCI was 1.6 times greater than that of the GP. Deaths due to cardiovascular disease (39.8%), neoplasms (22%), and infection (9.9%) were most often reported. Individuals with an SCI due to a vascular etiology indicated the greatest burden of mortality from infection compared with the GP (SMR 5.4; 95% CI, 3.1 to 9.2). CONCLUSIONS: Cause-specific SMRs varied according to etiology. This supports the need for targeted clinical care and follow-up. Cardiovascular disease, neoplasms, and infection, emerged as main causes of death following NTSCI and should thus be targets for future research and differential clinical management approaches.
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Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Infecciones/mortalidad , Neoplasias/mortalidad , Traumatismos de la Médula Espinal/epidemiología , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Traumatismos de la Médula Espinal/etiología , Suiza/epidemiología , Adulto JovenRESUMEN
Autonomous animal locomotion, such as swimming, is modulated by neuronal networks acting on cilia or muscles. Understanding how these networks are formed and coordinated is a complex scientific problem, which requires various technical approaches. Among others, behavioral studies of developing animals treated with exogenous substances have proven to be a successful approach for studying the functions of neuronal networks. One such substance crucial for the proper development of the nervous system is the vitamin A-derived morphogen retinoic acid (RA). In the larva of the marine annelid Platynereis dumerilii , for example, RA is involved in the specification and differentiation of individual neurons and responsible for orchestrating the swimming behavior of the developing larva. Here, we report a workflow to analyze the effects of RA on the locomotion of the P. dumerilii larva. We provide a protocol for both the treatment with RA and the recording of larval swimming behavior. Additionally, we present a pipeline for the analysis of the obtained data in terms of swimming speed and movement trajectory. This chapter thus summarizes the methodology for analyzing the effects of a specific drug treatment on larval swimming behavior. We expect this approach to be readily adaptable to a wide variety of pharmacological compounds and aquatic species.
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Anélidos/fisiología , Neuronas/citología , Tretinoina/farmacología , Animales , Organismos Acuáticos/fisiología , Conducta Animal/efectos de los fármacos , Tipificación del Cuerpo , Diferenciación Celular/efectos de los fármacos , Larva/fisiología , Neuronas/efectos de los fármacos , Natación/fisiología , Flujo de TrabajoRESUMEN
The knowledge of groundwater residence times in (vulnerable) aquifers is essential for the sustainable management of the associated groundwater resources. A powerful tool for related investigations is the application of naturally occurring radioisotopes as water age indicators. However, due to the limited number of suitable (i.e. omnipresent, short-lived and easily detectable) radionuclides only few studies focus on groundwater ages below one year. A natural radionuclide that does have the potential to cover this time range is 35S (87.4 day half-life). 35S is continually produced in the upper atmosphere and transferred with the rain to the groundwater. Since no natural sources of 35S exist in the subsurface the decrease of the 35S activity concentration in such young groundwater can be used for the determination of its age. Still, 35S activities in precipitation (and hence even more in groundwater) are very low and necessitate appropriate analytical protocols based on liquid scintillation counting (LSC). This turns out to be challenging due to the required large sample volumes and due to potentially high SO42- loads of the samples, both limiting the range of possible applications of 35S as indicator for short groundwater residence times. In the paper we present an improved straightforward LSC based approach for the detection of 35S in natural water samples. We recommend using Insta-Gel Plus as scintillation cocktail for allowing a homogeneous suspension of 35S-containing BaSO4 in the cocktail. The recommended improvements in instrument setting concern the LSC (TriCarb 3170 Tr/SL) counting window, the pulse decay discriminator setting and the delay before burst setting. The settings allow measuring low activity concentrations of 35S, which was previously pre-concentrated from natural water samples, containing SO42- loads of up to 1500â¯mg with a reasonably high statistical reliability.
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Agua Subterránea/química , Monitoreo de Radiación/métodos , Contaminantes Radiactivos del Agua/análisis , Conteo por Cintilación , Radioisótopos de Azufre/análisisAsunto(s)
Carcinoma Basocelular/diagnóstico , Cirugía de Mohs , Patología Quirúrgica/métodos , Neoplasias Cutáneas/diagnóstico , Coloración y Etiquetado/métodos , Carcinoma Basocelular/patología , Carcinoma Basocelular/cirugía , Colorantes/química , Eosina Amarillenta-(YS)/química , Estudios de Factibilidad , Hematoxilina/química , Humanos , Microscopía , Adhesión en Parafina , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
Continuous powder feeding is a critical step in continuous manufacturing of solid dosage forms, as this unit operation should ensure the mass flow consistency at the desired powder feed rate to guarantee the process throughput and final product consistency. In this study, twin-screw feeding of a pharmaceutical formulation (i.e., blend) existing of a highly dosed very poorly flowing active pharmaceutical ingredient (API) leading to insufficient feeding capacity was investigated. Furthermore, the API showed very high batch-to-batch variability in raw material properties dominating the formulation blend properties. Formulation changes were evaluated to improve the flowability of the blends and to mitigate the impact of API batch-to-batch variability on the twin-screw feeding. Herewith, feeding evaluation tests and an extensive material characterization of the reformulated blends were performed to assess the impact of the formulation changes upon continuous twin-screw feeding. The transfer of the glidant from extra-granular to intra-granular phase allowed to improve the flowability of the blends. A sufficient feeding capacity for the downstream process and a mitigation of the impact of batch-to-batch variability of the API upon twin-screw feeding of the blends could be achieved. No effect of the formulation or of the API properties on the feeding stability was observed. The material characterization of the blends allowed identifying the material attributes which were critical for continuous twin-screw feeding (i.e., bulk density, mass charge and powder cohesiveness).
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Química Farmacéutica/métodos , Excipientes/química , Preparaciones Farmacéuticas/administración & dosificación , Tecnología Farmacéutica/métodos , Composición de Medicamentos/métodos , Preparaciones Farmacéuticas/química , PolvosRESUMEN
AIM: Neurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration-related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalization affects not only calbindin calcium binding capacity, but also calcium-sensitive mitochondrial-associated signalling, causing mitochondrial calcium overload and thereby Purkinje neurone death. METHODS: Immunohistochemically, we evaluated cerebellar organotypic slice cultures of rat brains after inducing PCD through the application of Yo antibody-positive PCD patient sera or purified antibodies against CDR2 and CDR2L how pharmacologically biased mitochondrial signalling affected PCD pathology. RESULTS: We found that Yo antibody internalization into Purkinje neurons caused depletion of Purkinje neurone calbindin-immunoreactivity, cannabinoid 1 receptor over-activation and alterations in the actions of the mitochondria permeability transition pore (MPTP), voltage-dependent anion channels, reactive oxygen species (ROS) and Na+ /Ca2+ exchangers (NCX). The pathological mechanisms caused by Yo antibody binding to CDR2 or CDR2L differed between the two targets. Yo-CDR2 binding did not alter the mitochondrial calcium retention capacity, cyclophilin D-independent opening of MPTP or activity of NCX. CONCLUSION: These findings suggest that minimizing intracellular calcium overload toxicity either directly with cyclosporin-A or indirectly with cannabidiol or the ROS scavenger butylated hydroxytoluene promotes mitochondrial calcium homeostasis and may therefore be used as future neuroprotective therapy for PCD patients.
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Calcio/metabolismo , Mitocondrias/patología , Degeneración Cerebelosa Paraneoplásica/patología , Células de Purkinje/patología , Animales , Autoanticuerpos/inmunología , Enfermedades Cerebelosas/patología , Cerebelo/patología , Humanos , Mitocondrias/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Degeneración Cerebelosa Paraneoplásica/inmunología , Células de Purkinje/metabolismo , RatasRESUMEN
BACKGROUND: For safe excision of malignant skin tumours, complete negative surgical margins are mandatory. The gold standard for analysis is frozen sections or paraffin-embedded haematoxylin and eosin (H&E)-stained slides. The production of H&E-stained slides is time-consuming (>20 h) while wounds remain unclosed. An upcoming method is confocal laser scanning microscopy (CLSM), a technique that scans unfixed fresh tissue rapidly. OBJECTIVE: Evaluation of the process to generate and analyse CLSM images and assessment of the accuracy to detect basal cell carcinoma (BCC) tissue. METHODS: Digital microscopic images were generated by the Histolog Scanner v1 from 544 fresh specimens of 148 BCCs that had been stained with a 0.01% proflavine solution. CLSM images were compared to the histological diagnoses of the corresponding H&E-stained slides. RESULTS: A total of 525 images could be analysed. The sensitivity was 73% (95% CI = [65.27%; 80.47%]), and the specificity was 96% (95% CI = [93.40%; 97.60%]). Detection of BCCs in punch biopsies was certainly detected (sensitivity of 100%). The median total time to generate and evaluate a CLSM image was 5.17 min (maximum 20.17 min and minimum 2.05 min). The greatest challenge was flattening the specimen to assure complete representation of the surgical margins. CONCLUSION: Confocal laser scanning microscopy is a time-saving and very effective alternative to classical paraffin-embedded or frozen sections. Patient treatment could be improved due to shorter hospital stays or faster outpatient therapy due to reduced intervals between surgical stages. Diagnostic accuracy of the microscope used still must be improved.
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Carcinoma Basocelular/patología , Carcinoma Basocelular/cirugía , Microscopía Confocal/métodos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Adulto , Anciano , Biopsia con Aguja , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Cirugía de Mohs/métodos , Tempo Operativo , Parafina/farmacología , Estudios Prospectivos , Sensibilidad y Especificidad , Adhesión del TejidoRESUMEN
STUDY DESIGN: Observational cohort study. OBJECTIVE: To investigate survival and life expectancy after NTSCI in Switzerland according to etiology. SETTING: Specialized rehabilitation centers in Switzerland. METHODS: Longitudinal data from the Swiss Spinal Cord Injury (SwiSCI) medical records study were used. Adjusted hazard ratios (HRs) and life expectancies were estimated using flexible parametric survival modeling. RESULTS: One thousand four hundred and fifty individuals were admitted to first rehabilitation for NTSCI between 1990 and 2011, contributing 6137 cumulative person-years at risk and 528 deaths. With reference to persons with a degenerative disc disorder, the HR for mortality in individuals with NTSCIs from infections was 1.42 (95% CI 0.99-2.04), while risk in those with NTSCIs from vascular disorders was 1.28 (95% CI 0.97-1.68). Mortality risk was most pronounced in individuals with NTSCIs from malignant neoplasms (HR 6.32, 95% CI 4.79-8.34). Exemplified for males with an attained age of 60 years, a malignant etiology was associated with 1.7 life years remaining (LYR), as compared to 10.1 LYR for non-malignant etiologies. Males with an attained age of 60 years and a degenerative disc etiology were estimated to have 12.9 LYR. CONCLUSIONS: This study contributes an evidence base for risk factors of mortality after NTSCI, reducing a considerable knowledge gap in survival after NTSCI. Survival and life expectancy estimates were highly differential between etiological groups, indicating a need for a heterogeneous clinical approach and dynamic health-care provisions for this growing population.
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Traumatismos de la Médula Espinal/mortalidad , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Esperanza de Vida , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Centros de Rehabilitación , Estudios Retrospectivos , Factores de Riesgo , Traumatismos de la Médula Espinal/etiología , Traumatismos de la Médula Espinal/rehabilitación , Análisis de Supervivencia , Suiza , Adulto JovenRESUMEN
Vector autoregressive models (VAR models) are often used to model and to analyze multivariate time series, especially to provide short-term forecasts. A common method of estimating coefficients of these VAR models is solving the Yule- Walker equations. This work introduces and investigates a method to set up "sparse" VAR models, in order to obtain a comparable prognosis quality with significantly fewer coefficients. For this purpose, an artificial neural network was programmed in Python with TensorFlow. Sparsity arises from the implementation of regularization algorithms.Based on simulated data and an ECG, we show that a comparable prognosis quality can be achieved with significantly fewer coefficients. In addition, sparse VAR models can also be determined if the data would actually lead to an underdetermined system of equations. Thus, sparse VAR models may help to classify short epochs of biosignals, e.g. P-waves or QRS-complexes.
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Algoritmos , Técnicas Biosensibles , Redes Neurales de la Computación , Simulación por ComputadorRESUMEN
Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product development and product life cycle leading to changes in physical material attributes which can potentially affect their processability. Recent literature highlights the need for a global approach to understand the link between material synthesis, material variability, process and product quality. The study described in this article aims at explaining the raw material variability of an API using extensive material characterization on a restricted number of representative batches using multivariate data analysis. It is part of a larger investigation trying to link the API drug substance manufacturing process, the resulting physical API raw material attributes and the drug product continuous manufacturing process. Eight API batches produced using different synthetic routes, crystallization, drying, delumping processes and processing equipment were characterized, extensively. Seventeen properties from seven characterization techniques were retained for further analysis using Principal Component Analysis (PCA). Three principal components (PCs) were sufficient to explain 92.9% of the API raw material variability. The first PC was related to crystal length, agglomerate size and fraction, flowability and electrostatic charging. The second PC was driven by the span of the particle size distribution and the agglomerates strength. The third PC was related to surface energy. Additionally, the PCA allowed to summarize the API batch-to-batch variability in only three PCs which can be used in future drug product development studies to quantitatively evaluate the impact of the API raw material variability upon the drug product process. The approach described in this article could be applied to any other compound which is prone to batch-to-batch variability.
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Preparaciones Farmacéuticas/química , Química Farmacéutica/métodos , Cristalización/métodos , Tamaño de la Partícula , Análisis de Componente Principal/métodos , Tecnología Farmacéutica/métodosRESUMEN
BACKGROUND: Rehabilitative health care is paying increasing attention to multimorbid people with 2 and more coexistent chronic diseases of sociomedical relevance. METHODS: Terms, requirements, design, configuration, challenges and supply of sociomedical rehabilitation were described in part I. A project group of the Medical Advisory Board of the Federal Rehabilitation Council describes manifold fields of actions to be taken in the rehabilitation of persons with multimorbidity. RESULTS: The actions proposed range from reviewing existing forms of management to identifying rehabilitative needs and initiating accurately fitting interventions, sensitizing and enlarging competences of involved personnel, considering multimorbidity in guidelines and further research on questions still open.
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Atención a la Salud , Multimorbilidad , Rehabilitación , Predicción , Alemania , Humanos , Rehabilitación/tendenciasRESUMEN
BACKGROUND: Rehabilitative health care is increasingly focusing its attention on multimorbid people with 2 and more coexistent chronic diseases of sociomedical relevance. METHODS: After defining the term "multimorbidity" in the context of rehabilitative health care, an exploratory overview of the prevalence and clinical implication of this condition as reported in the literature was drafted. Based on a case history, special attention was paid to general as well as special challenges regarding design, configuration and supply of sociomedical rehabilitative care. Consensus was achieved with the Health Advisory Board of the German Federal Rehabilitation Council. RESULTS: The proposed actions necessary for the healthcare of persons with multimorbidity include specific function-oriented individual assessment of needs via the distinctive allocation, selection and performance of rehabilitative procedures as well as post-rehabilitative care until the patient's reintegration into his social environment.