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Dopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area generally respond to aversive stimuli or the absence of expected rewards with transient inhibition of firing rates, which can be recapitulated with activation of the lateral habenula (LHb) and eliminated by lesioning the intermediating rostromedial tegmental nucleus (RMTg). However, a minority of DA neurons respond to aversive stimuli, such as foot shock, with a transient increase in firing rate, an outcome that rarely occurs with LHb stimulation. The degree to which individual neurons respond to these two stimulation modalities with the same response phenotype and the role of the RMTg is not known. Here, we record responses from single SN DA neurons to alternating activation of the LHb and foot shock in male rats. Lesions of the RMTg resulted in a shift away from inhibition to no response during both foot shock and LHb stimulation. Furthermore, lesions unmasked an excitatory response during LHb stimulation. The response correspondence within the same neuron between the two activation sources was no different from chance in sham controls, suggesting that external inputs rather than intrinsic DA neuronal properties are more important to response outcome. These findings contribute to a literature that shows a complex neurocircuitry underlies the regulation of DA activity and, by extension, behaviors related to learning, anhedonia, and cognition.
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Neuronas Dopaminérgicas , Habénula , Sustancia Negra , Animales , Masculino , Habénula/fisiología , Neuronas Dopaminérgicas/fisiología , Sustancia Negra/fisiología , Electrochoque , Potenciales de Acción/fisiología , Ratas , Estimulación Eléctrica , Ratas Sprague-Dawley , Área Tegmental Ventral/fisiologíaRESUMEN
The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.
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Introduction: Clinically relevant sex differences have been noted in a number of affective, behavioral, cognitive, and neurological health disorders. Midbrain dopamine neurons are implicated in several of these same disorders and consequently are under investigation for their potential role in the manifestation of these sex differences. The lateral habenula exerts significant inhibitory control over dopamine neuronal firing, yet little is known about sex differences in this particular neurocircuit. Methods: We performed in vivo, single unit, extracellular recordings of dopamine neurons in female and male anesthetized rats in response to single pulse stimulation of the lateral habenula. In addition, we assessed baseline firing properties of lateral habenula neurons and, by immunochemical means, assessed the distribution of estrogen receptor alpha cells in the lateral habenula. Results: Habenula-induced inhibition of dopamine neuronal firing is reduced in female rats relative to male rats. In addition, male rats had a higher prevalence of rebound excitation. Furthermore, the firing pattern of lateral habenula neurons was less variable in female rats, and female rats had a higher density of estrogen receptor alpha positive cells in the lateral habenula. Discussion: We found that the dopamine neuronal response to habenular stimulation is both qualitatively and quantitatively different in female and male rats. These novel findings together with reports in the contemporary literature lead us to posit that the sex difference in dopamine inhibition seen here relate to differential firing properties of lateral habenula neurons resulting from the presence of sex hormones. Further work is needed to test this hypothesis, which may have implications for understanding the etiology of several mental health disorders including depression, schizophrenia, and addiction.
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OBJECTIVES: Vaccine hesitancy is a public health challenge highlighted during the COVID-19 pandemic. This study sought to determine the prevalence and explanatory factors leading to COVID-19 vaccine hesitancy in the Jamaican population to inform vaccination strategies. STUDY DESIGN: This was an exploratory cross-sectional study. METHODS: An exploratory survey was distributed electronically between September and October 2021 to gather information on COVID-19 vaccination behaviour and beliefs among the Jamaican population. Data were expressed as frequencies and analysed using Chi-squared followed by multivariate logistic regressions. Significant analyses were determined at P < 0.05. RESULTS: Of the 678 eligible responses, most were females (71.5%, n = 485), between ages 18-45 years (68.2%, n = 462), had tertiary education (83.4%, n = 564) and were employed (73.4%, n = 498), with 10.6% (n = 44) being healthcare workers. COVID-19 vaccine hesitancy was present in 29.8% (n = 202) of the survey population, mainly because of safety and efficacy concerns and a general lack of reliable information about the vaccines. The likelihood of hesitancy increased amongst respondents under 36 years (odds ratio [OR] 6.8, 95% confidence interval [CI] 3.6, 12.9), those who delayed initial acceptance of vaccines (OR 2.7, 95% CI 2.3, 3.1); parents for their children and with long waits at vaccination centres. Likelihood of hesitancy decreased for respondents over 36 years (OR 3.7, 95% CI 1.8, 7.8) and with vaccine support from pastors/religious leaders (OR 1.6, 95% CI 1.1, 2.4). CONCLUSIONS: Vaccine hesitancy was more prevalent in younger respondents who were never exposed to the effects of vaccine-preventable diseases. Religious leaders had more influence than healthcare workers to increase vaccine uptake.
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Vacunas contra la COVID-19 , COVID-19 , Niño , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Masculino , Vacunas contra la COVID-19/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Prevalencia , Estudios Transversales , Países en Desarrollo , Pandemias , VacunaciónRESUMEN
Charge diffusion and extraction are crucial steps in the operation of solar cells. Here we show that time-resolved photoluminescence can be used to study electron diffusion in hybrid perovskite films and subsequent transfer to the adjacent electron extraction layer. As diffusion and transfer to the extraction layer are consecutive processes, they can be hard to distinguish, but by exciting from each side of the sample we can separate them and identify which process limits charge extraction. We find that the introduction of a fullerene monolayer between the methylammonium lead iodide (MAPbI3) and the electron-transporting SnO2 layers greatly increases the electron transfer velocity between them to the extent that electron diffusion limits the rate of electron extraction. Our results suggest that increasing the electron diffusion coefficient in MAPbI3 would further enhance the electron extraction rate, which could result in more efficient n-i-p type solar cells.
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INTRODUCTION: Kuwait has a shortage of radiologists, especially in mammography, resulting in increased workload and longer waiting times for women receiving imaging investigations. This study looked at how radiographers and radiologists perceived radiographers' role extension (RE) in mammography, and whether this could reduce radiologist workload, thereby improving patient service and waiting times. METHODS: A single case study design with 10 radiographers (mammographers) and 10 radiologists was undertaken across multiple sites: hospitals, screening clinics and specialist centres in Kuwait. Data included individual semi-structured interviews, documentary analysis and field notes. Perceptions were examined under a theoretical framework, Abbotts' System of Professions. RESULTS: Two main themes were identified, firstly in examining the current role of radiographers in mammography and areas of interest for extending role, this highlighted insufficient knowledge of the concept. The second focused on in-depth understanding of drivers and barriers to RE in mammography, both groups opposed radiographers performing extended tasks without radiologist supervision. CONCLUSION: Radiologists and radiographers' attitudes were influenced by concepts of professional identity and professional identity formation. Insufficient professional knowledge negatively affected the radiographers' readiness to undertake RE in mammography. Radiologists are reluctant to blur boundaries, enabling them to maintain and control jurisdiction of their own profession and that of radiographers, thereby, as discussed in Abbott's theory, limiting impact on workload or waiting times. IMPLICATIONS FOR PRACTICE: Whilst RE is limited, to improve workload and patient waiting times, setting up an educational programme for radiographers specialising in mammography would be an important step to extending the radiographers' role. The study highlighted a need to educate radiographers to undertake breast ultrasound and amend policy to introduce training programmes for radiographers. Radiographer rotation across the various radiographic modalities negatively affected radiographers' performance, placing well-trained radiographers permanently within the mammography department should improve experience and overall skills.
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Técnicos Medios en Salud , Radiólogos , Actitud , Femenino , Humanos , Kuwait , MamografíaRESUMEN
The present study investigated the relationship between perceived racial discrimination and prescription drug misuse (PDM) among Asian, Black, and Latinx Americans during the COVID-19 crisis. U.S. racial/ethnic minorities may have been uniquely affected by two national and one global pandemic: the opioid crisis, racism, and COVID-19. Opioid death rates increased among many groups prior to the pandemic. This country witnessed an increase in racialized acts against people of color across the spectrum in the spring and summer months of the world's COVID-19 outbreak. While studies have shown a clear link between perceived racial discrimination and substance abuse outside of the global pandemic, no identified studies have done so against the backdrop of a global health pandemic. Separate hierarchical regressions revealed a significant association between perceived racial discrimination and PDM for Black Americans, Asian Americans, and Latinx individuals. Findings build on the scant literature on PDM in diverse samples and establish a relationship between perceived racial discrimination and PDM, as previously identified for other abused substances. Future post-pandemic substance misuse interventions should consider the influence of perceived racial discrimination as they help individuals recover from the aftermath of this stressful trifecta.
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COVID-19 , Mal Uso de Medicamentos de Venta con Receta , Racismo , Minorías Étnicas y Raciales , Humanos , Pandemias , SARS-CoV-2RESUMEN
Implementation of wildfire- and climate-adaptation strategies in seasonally dry forests of western North America is impeded by numerous constraints and uncertainties. After more than a century of resource and land use change, some question the need for proactive management, particularly given novel social, ecological, and climatic conditions. To address this question, we first provide a framework for assessing changes in landscape conditions and fire regimes. Using this framework, we then evaluate evidence of change in contemporary conditions relative to those maintained by active fire regimes, i.e., those uninterrupted by a century or more of human-induced fire exclusion. The cumulative results of more than a century of research document a persistent and substantial fire deficit and widespread alterations to ecological structures and functions. These changes are not necessarily apparent at all spatial scales or in all dimensions of fire regimes and forest and nonforest conditions. Nonetheless, loss of the once abundant influence of low- and moderate-severity fires suggests that even the least fire-prone ecosystems may be affected by alteration of the surrounding landscape and, consequently, ecosystem functions. Vegetation spatial patterns in fire-excluded forested landscapes no longer reflect the heterogeneity maintained by interacting fires of active fire regimes. Live and dead vegetation (surface and canopy fuels) is generally more abundant and continuous than before European colonization. As a result, current conditions are more vulnerable to the direct and indirect effects of seasonal and episodic increases in drought and fire, especially under a rapidly warming climate. Long-term fire exclusion and contemporaneous social-ecological influences continue to extensively modify seasonally dry forested landscapes. Management that realigns or adapts fire-excluded conditions to seasonal and episodic increases in drought and fire can moderate ecosystem transitions as forests and human communities adapt to changing climatic and disturbance regimes. As adaptation strategies are developed, evaluated, and implemented, objective scientific evaluation of ongoing research and monitoring can aid differentiation of warranted and unwarranted uncertainties.
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Incendios , Incendios Forestales , Ecosistema , Bosques , Humanos , América del NorteRESUMEN
Common carp (Cyprinus carpio) are an invasive species of the rivers and waterways of south-eastern Australia, implicated in the serious decline of many native fish species. Over the past 50 years a variety of control options have been explored, all of which to date have proved either ineffective or cost prohibitive. Most recently the use of cyprinid herpesvirus 3 (CyHV-3) has been proposed as a biocontrol agent, but to assess the risks and benefits of this, as well as to develop a strategy for the release of the virus, a knowledge of the fundamental processes driving carp distribution and abundance is required. To this end, we developed a novel process-based modelling framework that integrates expert opinion with spatio-temporal datasets via the construction of a Bayesian Network. The resulting weekly networks thus enabled an estimate of the habitat suitability for carp across a range of hydrological habitats in south-eastern Australia, covering five diverse catchment areas encompassing in total a drainage area of 132,129 km2 over a period of 17-27 years. This showed that while suitability for adult and subadult carp was medium-high across most habitats throughout the period, nevertheless the majority of habitats were poorly suited for the recruitment of larvae and young-of-year (YOY). Instead, high population abundance was confirmed to depend on a small number of recruitment hotspots which occur in years of favourable inundation. Quantification of the underlying ecological drivers of carp abundance thus makes possible detailed planning by focusing on critical weaknesses in the population biology of carp. More specifically, it permits the rational planning for population reduction using the biocontrol agent, CyHV-3, targeting areas where the total population density is above a "damage threshold" of approximately 100 kg/ha.
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Carpas , Enfermedades de los Peces , Infecciones por Herpesviridae , Animales , Australia , Teorema de Bayes , Herpesviridae , Especies IntroducidasRESUMEN
Understanding the function of social networks can make a critical contribution to achieving desirable environmental outcomes. Social-ecological systems are complex, adaptive systems in which environmental decision makers adapt to a changing social and ecological context. However, it remains unclear how multiple social influences interact with environmental feedbacks to generate environmental outcomes. Based on national-scale survey data and a social-ecological agent-based model in the context of voluntary private land conservation, our results suggest that social influences can operate synergistically or antagonistically, thereby enabling behaviors to spread by two or more mechanisms that amplify each other's effects. Furthermore, information through social networks may indirectly affect and respond to isolated individuals through environmental change. The interplay of social influences can, therefore, explain the success or failure of conservation outcomes emerging from collective behavior. To understand the capacity of social influence to generate environmental outcomes, social networks must not be seen as 'closed systems'; rather, the outcomes of environmental interventions depend on feedbacks between the environment and different components of the social system.
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AIM: To inform the activity of the newly formed Radiology Academic Network for Trainees (RADIANT) regarding the current level of interest, engagement, and barriers experienced by UK radiology trainees to undertake research. MATERIALS AND METHODS: A web-based survey containing nine questions was sent to the UK radiology training programme directors for distribution to trainees. The survey was also distributed to all trainee members of the RADIANT network. This led to 224 responses over a period of 2 months. RESULTS: A large proportion of respondents indicated a desire to participate in research in the next 12 months 72.3% (n=162). The most frequently reported barriers to research were lack of time (60.7%, n=136), lack of awareness of local/departmental opportunities (53.6%, n=120), and limited experience in research statistics (46%, n=103). The most favoured factor that would improve access to research was structured research training opportunities, qualified as a project with clear goals and timeline (71%, n=159), protected time for research (68.8%, n=154), and local or national trainee research networks (40.2%, n=90 and 37.1%, n=83, respectively). CONCLUSION: Many radiology trainees would like to participate in research, but multiple barriers exist. The formation of RADIANT is seen as a key part of a multifaceted approach to improving access to quality research activity alongside support from local and regional training bodies.
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Investigación Biomédica , Selección de Profesión , Radiología/educación , Educación de Postgrado en Medicina , Humanos , Motivación , Encuestas y Cuestionarios , Factores de Tiempo , Reino UnidoRESUMEN
Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment.
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Estimulación Encefálica Profunda/métodos , Ritmo Gamma/fisiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Núcleo Subtalámico/fisiopatología , Anciano , Antiparkinsonianos , Femenino , Humanos , Levodopa , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: The Covid-19 crisis continues to profoundly impact on radiotherapy practice in the UK. We explore the views of therapeutic radiographer students on entering their first post in unique circumstances as a means to evaluate the support that may minimise negative impacts on their transition to practitioners. METHOD: Focus groups were conducted outside of students' final year educational programme and immediately prior to them starting work. Qualitative data were analysed using a framework analysis. RESULTS: Emergent themes from the eleven participants were: Covid-19 as a layer on top of underlying anxieties; Degree of readiness for imminent psychological, emotional and practical challenges; Feeling valued as a health professional/radiographer at this time; A mixed student and qualified staff professional identity as HCPC temporary registrants. CONCLUSION: Uncertainties related to Covid-19 were seen to add a destabilising component to existing anxieties and challenges. In this context, there are significant risks of impaired professional socialisation due to incongruence between students' expectations and the reality in clinical departments. IMPLICATIONS FOR PRACTICE: Informed academic support and flexible clinical preceptorship that address anxieties and congruence barriers are vital to guide new practitioners through a health crisis that presents significant challenges but also opportunity for professional development.
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COVID-19/epidemiología , Motivación , Pandemias , Preceptoría , Radiografía , Radiología/educación , Estudiantes de Medicina/psicología , Adulto , Ansiedad/etiología , COVID-19/diagnóstico por imagen , Femenino , Grupos Focales , Humanos , Identificación Psicológica , Masculino , Sistema de Registros , SARS-CoV-2 , Interacción Social , Incertidumbre , Gales/epidemiología , Adulto JovenRESUMEN
Background: Acute kidney injury (AKI) is common among patients admitted to the intensive care unit (ICU). It is an independent risk factor for morbidity and mortality. The optimal timing of renal replacement therapy (RRT) remains unknown, resulting in a wide variation in observed current practices. There is a paucity of data on current practices within ICUs in South Africa. Objectives: To describe current practices in the timing of RRT in patients with AKI admitted to the ICU. The secondary objectives were to describe the patient characteristics, severity of illness scores, staging at initiation of RRT, outcome at ICU discharge, and to estimate and describe delays in the initiation of RRT. Methods: A retrospective, descriptive study was conducted in an adult academic ICU in Soweto from 1 January 2014 to 31 December 2015. Results: There were 2 152 ICU admissions over the 2 years. Less than a tenth of the patients (3.5%; n=76) required RRT and the majority had sepsis (83%). The most common indication for RRT was oliguria/anuria (50%; n=38), followed by worsening urea/creatinine (29%; n=22), metabolic acidosis (11.8%; n=9), refractory hyperkalaemia (5.3%; n=4), fluid overload (2.6%; n=2) and other (1.3%; n=1). More than half of the patients (55%; n=42) had RRT instituted on admission day (D0 ), while 45% (n=34) had RRT initiated after D0 (D1-21). RRT was initiated at stage 3 AKI in 90% and 94% of D0 RRT group and D1-21 RRT group, respectively. The median (interquartile range (IQR)) time to starting RRT was 4 (4) hours once the decision to initiate RRT was made. The composite outcome of death, RRT dependence and diuretic dependence at ICU discharge was 21% and there was no difference between the two groups (p=0.22). The ICU mortality was 3%. Conclusion: The sampled population was young, predominantly male and had post emergency surgery with a high burden of sepsis and HIV. The observed current threshold for RRT was late (stage 3 AKI with classic/emergent indications) with outcomes comparable with the reviewed literature. Contributions of the study: The present study adds insight into the practice of initiating RRT in patients admitted to the ICU with AKI. These data have previously not been described in the South African context. The patient population differed from the literature in that they were young, predominantly male and had post-emergency surgery with a high burden of sepsis and HIV.
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AIM: To determine whether machine learning-based radiomic feature analysis of baseline integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) computed tomography (CT) predicts disease progression in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (SCC) receiving (chemo)radiotherapy. MATERIALS AND METHODS: Patients with larynx and hypopharynx SCC treated with definitive (chemo)radiotherapy at a specialist cancer centre undergoing pre-treatment PET-CT between 2008 and 2017 were included. Tumour segmentation and radiomic analysis was performed using LIFEx software (University of Paris-Saclay, France). Data were assigned into training (80%) and validation (20%) cohorts adhering to TRIPOD guidelines. A random forest classifier was created for four predictive models using features determined by recursive feature elimination: (A) PET, (B) CT, (C) clinical, and (D) combined PET-CT parameters. Model performance was assessed using area under the curve (AUC) receiver operating characteristic (ROC) analysis. RESULTS: Seventy-two patients (40 hypopharynx 32 larynx tumours) were included, mean age 61 (range 41-77) years, 50 (69%) were men. Forty-five (62.5%) had chemoradiotherapy, 27 (37.5%) had radiotherapy alone. Median follow-up 26 months (range 12-105 months). Twenty-seven (37.5%) patients progressed within 12 months. ROC AUC for models A, B, C, and D were 0.91, 0.94, 0.88, and 0.93 in training and 0.82, 0.72, 0.70, and 0.94 in validation cohorts. Parameters in model D were metabolic tumour volume (MTV), maximum CT value, minimum standardized uptake value (SUVmin), grey-level zone length matrix (GLZLM) small-zone low grey-level emphasis (SZLGE) and histogram kurtosis. CONCLUSION: FDG PET-CT derived radiomic features are potential predictors of early disease progression in patients with locally advanced larynx and hypopharynx SCC.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Aprendizaje Automático , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Femenino , Fluorodesoxiglucosa F18 , Humanos , Hipofaringe/diagnóstico por imagen , Hipofaringe/patología , Neoplasias Laríngeas/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Valor Predictivo de las Pruebas , RadiofármacosRESUMEN
Composite endpoints reveal the tendency for statistical convention to arise locally within subfields. Composites are familiar in cardiovascular trials, yet almost unknown in sepsis. However, the VITAMINS trial in patients with septic shock adopted a composite of mortality and vasopressor-free days, and an ordinal scale describing patient status rapidly became standard in COVID studies. Aware that recent use could incite interest in such endpoints, we are motivated to flag their potential value and pitfalls for sepsis research and COVID studies.
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COVID-19/epidemiología , Determinación de Punto Final/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , COVID-19/terapia , Determinación de Punto Final/métodos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodosRESUMEN
BACKGROUND: The growth pattern of colorectal cancer is seldom investigated. This cohort study aimed to explore tumour growth rate in colorectal cancers managed non-surgically or deemed not resectable, and to determine its implication for prognosis. METHODS: Consecutive patients with colonic or rectal adenocarcinoma were identified through the colorectal multidisciplinary team database at Leeds Teaching Hospitals NHS Trust over a 2-year interval. Patients who received no treatment (surgery, stenting, colonic defunctioning procedures, chemotherapy, radiotherapy) and who underwent CT twice more than 5 weeks apart were included. Multidetector CT/three-dimensional image analysis was performed independently by three experienced radiologists. RESULTS: Of 804 patients reviewed, 43 colorectal cancers were included in the final analysis. Median age at first CT was 80 (73-85) years and the median interval between scans was 150 (i.q.r. 72-471) days. An increase in T category was demonstrated in 31 of 43 tumours, with a median doubling time of 211 (112-404) days. The median percentage increase in tumour volume was 34·1 (13·3-53·9) per cent per 62 days. The all-cause 3-year mortality rate was 81 per cent (35 of 43) with a median survival time of 1·1 (0·4-2·2) years after the initial diagnostic scan. In those obstructed, the relative risk of death from subsequent perforation was 1·26 (95 per cent c.i. 1·07 to 1·49; P = 0·005). CONCLUSION: This study documented a median doubling time of 211 days, with a concerning suggestion of tumour progression, which has implications for the current management standard.
ANTECEDENTES: El patrón de crecimiento del CRC (colorectal cancer, CRC) ha sido poco investigado. El objetivo de este estudio de cohortes fue explorar la tasa de crecimiento tumoral en los pacientes con CRC no tratados quirúrgicamente o con tumores irresecables para determinar su valor pronóstico. MÉTODOS: Los pacientes consecutivos con adenocarcinoma de colon o recto se identificaron a partir de la base de datos del equipo multidisciplinario colorrectal del "Leeds Teaching Hospitals NHS Trust" durante un período de 2 años. Se incluyeron los pacientes que no recibieron tratamiento (cirugía, colocación de endoprótesis, procedimientos de desfuncionalización del colon, quimioterapia, radioterapia), en los que se obtuvieron tomografías computarizadas con > 5 semanas de diferencia. El análisis de imágenes TC/3D multidetector fue realizado de forma independiente por tres radiólogos expertos. RESULTADOS: De los 804 pacientes revisados, 43 CRCs se incluyeron en el análisis final con una mediana de 150 días (rango intercuartílico, interquartile range, IQR: 72-471) entre los escáners. La mediana de edad en el primer escáner era de 80 años (IQR: 73-85). En 31 (72%) casos, se demostró un aumento del estadio TNM del tumor, con un tiempo medio de duplicación del tamaño tumoral de 211 días (IQR: 112-404). La mediana de aumento porcentual del volumen del tumor era de un 34% cada 62 días (IQR: 13,3-53,9). La mortalidad por cualquier causa a los 3 años fue del 81% (35/43), con una mediana de supervivencia de 1,1 años (IQR: 0,4-2,2) desde el escáner inicial diagnóstico. El riesgo relativo de mortalidad como resultado de la obstrucción intestinal y perforación subsiguiente era de 1,26 (i.c. del 95% 1,07-1,49, P < 0,01). CONCLUSIÓN: Este estudio documentó una mediana de tiempo de duplicación del tamaño del tumor de 211 días, así como datos preocupantes de la progresión del tumor que podrían tener repercusión en el tratamiento estándar actual.
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Local field potentials (LFPs) may afford insight into the mechanisms of action of deep brain stimulation (DBS) and potential feedback signals for adaptive DBS. In Parkinson's disease (PD) DBS of the subthalamic nucleus (STN) suppresses spontaneous activity in the beta band and drives evoked resonant neural activity (ERNA). Here, we investigate how STN LFP activities change over time following the onset and offset of DBS. To this end we recorded LFPs from the STN in 14 PD patients during long (mean: 181.2 s) and short (14.2 s) blocks of continuous stimulation at 130 Hz. LFP activities were evaluated in the temporal and spectral domains. During long stimulation blocks, the frequency and amplitude of the ERNA decreased before reaching a steady state after ~70 s. Maximal ERNA amplitudes diminished over repeated stimulation blocks. Upon DBS cessation, the ERNA was revealed as an under-damped oscillation, and was more marked and lasted longer after short duration stimulation blocks. In contrast, activity in the beta band suppressed within 0.5 s of continuous DBS onset and drifted less over time. Spontaneous activity was also suppressed in the low gamma band, suggesting that the effects of high frequency stimulation on spontaneous oscillations may not be selective for pathological beta activity. High frequency oscillations were present in only six STN recordings before stimulation onset and their frequency was depressed by stimulation. The different dynamics of the ERNA and beta activity with stimulation imply different DBS mechanisms and may impact how these activities may be used in adaptive feedback.