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1.
Cereb Cortex ; 33(7): 3621-3635, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36045002

RESUMO

Neurons, even in the earliest sensory regions of cortex, are subject to a great deal of contextual influences from both within and across modality connections. Recent work has shown that primary sensory areas can respond to and, in some cases, discriminate stimuli that are not of their target modality: for example, primary somatosensory cortex (SI) discriminates visual images of graspable objects. In the present work, we investigated whether SI would discriminate sounds depicting hand-object interactions (e.g. bouncing a ball). In a rapid event-related functional magnetic resonance imaging experiment, participants listened attentively to sounds from 3 categories: hand-object interactions, and control categories of pure tones and animal vocalizations, while performing a one-back repetition detection task. Multivoxel pattern analysis revealed significant decoding of hand-object interaction sounds within SI, but not for either control category. Crucially, in the hand-sensitive voxels defined from an independent tactile localizer, decoding accuracies were significantly higher for hand-object interactions compared to pure tones in left SI. Our findings indicate that simply hearing sounds depicting familiar hand-object interactions elicit different patterns of activity in SI, despite the complete absence of tactile stimulation. These results highlight the rich contextual information that can be transmitted across sensory modalities even to primary sensory areas.


Assuntos
Mãos , Córtex Somatossensorial , Animais , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiologia , Tato/fisiologia , Neurônios/fisiologia , Imageamento por Ressonância Magnética , Mapeamento Encefálico
2.
J Neurosci ; 41(24): 5263-5273, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33972399

RESUMO

Most neuroimaging experiments that investigate how tools and their actions are represented in the brain use visual paradigms where tools or hands are displayed as 2D images and no real movements are performed. These studies discovered selective visual responses in occipitotemporal and parietal cortices for viewing pictures of hands or tools, which are assumed to reflect action processing, but this has rarely been directly investigated. Here, we examined the responses of independently visually defined category-selective brain areas when participants grasped 3D tools (N = 20; 9 females). Using real-action fMRI and multivoxel pattern analysis, we found that grasp typicality representations (i.e., whether a tool is grasped appropriately for use) were decodable from hand-selective areas in occipitotemporal and parietal cortices, but not from tool-, object-, or body-selective areas, even if partially overlapping. Importantly, these effects were exclusive for actions with tools, but not for biomechanically matched actions with control nontools. In addition, grasp typicality decoding was significantly higher in hand than tool-selective parietal regions. Notably, grasp typicality representations were automatically evoked even when there was no requirement for tool use and participants were naive to object category (tool vs nontools). Finding a specificity for typical tool grasping in hand-selective, rather than tool-selective, regions challenges the long-standing assumption that activation for viewing tool images reflects sensorimotor processing linked to tool manipulation. Instead, our results show that typicality representations for tool grasping are automatically evoked in visual regions specialized for representing the human hand, the primary tool of the brain for interacting with the world.


Assuntos
Mapeamento Encefálico/métodos , Mãos/fisiologia , Imageamento Tridimensional/métodos , Desempenho Psicomotor/fisiologia , Adolescente , Adulto , Encéfalo/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto Jovem
3.
J Infect Dis ; 222(6): 957-961, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32253432

RESUMO

Influenza viruses harboring treatment-emergent I38F/M/N/T substitutions in the polymerase acidic (PA) endonuclease exhibited reduced susceptibility to baloxavir and were associated with virus rebound and variable clinical response in clinical trials. US regulatory review of registrational trial data also identified treatment-emergent PA substitutions E23K in A/H1N1 viruses and E23G/K, A37T, and E199G in A/H3N2 viruses, which conferred reduced susceptibility to baloxavir, although to a lesser degree than I38F/M/N/T substitutions, and were associated with virus rebound. Although these non-I38 substitutions emerged less frequently than substitutions at I38, they represent alternate pathways to baloxavir virologic resistance and should be monitored accordingly.


Assuntos
Substituição de Aminoácidos , Farmacorresistência Viral , Influenza Humana/virologia , Mutação , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/genética , RNA Polimerase Dependente de RNA/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Dibenzotiepinas/farmacologia , Dibenzotiepinas/uso terapêutico , Humanos , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza B/classificação , Vírus da Influenza B/genética , Influenza Humana/tratamento farmacológico , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Orthomyxoviridae/classificação , Orthomyxoviridae/enzimologia , Piridonas/farmacologia , Piridonas/uso terapêutico , Resultado do Tratamento , Triazinas/farmacologia , Triazinas/uso terapêutico , Carga Viral
4.
Neuroimage ; 211: 116660, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32081784

RESUMO

Rapidly and accurately processing information from faces is a critical human function that is known to improve with developmental age. Understanding the underlying drivers of this improvement remains a contentious question, with debate continuing as to the presence of early vs. late maturation of face-processing mechanisms. Recent behavioural evidence suggests an important 'hallmark' of expert face processing - the face inversion effect - is present in very young children, yet neural support for this remains unclear. To address this, we conducted a detailed investigation of the neural dynamics of face processing in children spanning a range of ages (6-11 years) and adults. Uniquely, we applied multivariate pattern analysis (MVPA) to the electroencephalogram signal (EEG) to test for the presence of a distinct neural profile associated with canonical upright faces when compared both to other objects (houses) and to inverted faces. Results revealed robust discrimination profiles, at the individual level, of differentiated neural activity associated with broad face categorization and further with its expert processing, as indexed by the face inversion effect, from the youngest ages tested. This result is consistent with an early functional maturation of broad face processing mechanisms. Yet, clear quantitative differences between the response profile of children and adults is suggestive of age-related refinement of this system with developing face and general expertise. Standard ERP analysis also provides some support for qualitative differences in the neural response to inverted faces in children in contrast to adults. This neural profile is in line with recent behavioural studies that have reported impressively expert early face abilities during childhood, while also providing novel evidence of the ongoing neural specialisation between child and adulthood.


Assuntos
Desenvolvimento Infantil/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Reconhecimento Facial/fisiologia , Percepção Social , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem
5.
Neuroimage ; 195: 261-271, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30940611

RESUMO

Faces transmit a wealth of important social signals. While previous studies have elucidated the network of cortical regions important for perception of facial expression, and the associated temporal components such as the P100, N170 and EPN, it is still unclear how task constraints may shape the representation of facial expression (or other face categories) in these networks. In the present experiment, we used Multivariate Pattern Analysis (MVPA) with EEG to investigate the neural information available across time about two important face categories (expression and identity) when those categories are either perceived under explicit (e.g. decoding facial expression category from the EEG when task is on expression) or incidental task contexts (e.g. decoding facial expression category from the EEG when task is on identity). Decoding of both face categories, across both task contexts, peaked in time-windows spanning 91-170 ms (across posterior electrodes). Peak decoding of expression, however, was not affected by task context whereas peak decoding of identity was significantly reduced under incidental processing conditions. In addition, errors in EEG decoding correlated with errors in behavioral categorization under explicit processing for both expression and identity, however under incidental conditions only errors in EEG decoding of expression correlated with behavior. Furthermore, decoding time-courses and the spatial pattern of informative electrodes showed consistently better decoding of identity under explicit conditions at later-time periods, with weak evidence for similar effects for decoding of expression at isolated time-windows. Taken together, these results reveal differences and commonalities in the processing of face categories under explicit Vs incidental task contexts and suggest that facial expressions are processed to a richer degree under incidental processing conditions, consistent with prior work indicating the relative automaticity by which emotion is processed. Our work further demonstrates the utility in applying multivariate decoding analyses to EEG for revealing the dynamics of face perception.


Assuntos
Encéfalo/fisiologia , Emoções , Expressão Facial , Reconhecimento Facial/fisiologia , Adolescente , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Máquina de Vetores de Suporte , Adulto Jovem
6.
J Antimicrob Chemother ; 73(6): 1464-1478, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554263

RESUMO

Background: A global antimicrobial resistance (AMR) awareness intervention targeting the general public has been prioritized. Objectives: To evaluate the effectiveness of interventions that aim to change AMR awareness and subsequent stewardship behaviours amongst the public. Methods: Five databases were searched between 2000 and 2016 for interventions to change the public's AMR awareness and/or antimicrobial stewardship behaviours. Study designs meeting the Cochrane Effective Practice and Organization of Care (EPOC) criteria, non-controlled before-and-after studies and prospective cohort studies were considered eligible. Participants recruited from healthcare settings and studies measuring stewardship behaviours of healthcare professionals were excluded. Quality of studies was assessed using EPOC risk of bias criteria. Data were extracted and synthesized narratively. Registration: PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016050343). Results: Twenty studies were included in the review with nine meeting the EPOC criteria. The overall risk of bias was high. Nineteen studies were conducted in high-income countries. Mass media interventions were most common (n = 7), followed by school-based (n = 6) and printed material interventions (n = 6). Seventeen studies demonstrated a significant effect on changing knowledge, attitudes or the public's antimicrobial stewardship behaviours. Analysis showed that interventions targeting schoolchildren and parents have notable potential, but for the general public the picture is less clear. Conclusions: Our work provides an in-depth examination of the effectiveness of AMR interventions for the public. However, the studies were heterogeneous and the quality of evidence was poor. Well-designed, experimental studies on behavioural outcomes of such interventions are required.


Assuntos
Gestão de Antimicrobianos/métodos , Farmacorresistência Bacteriana , Conhecimentos, Atitudes e Prática em Saúde , Saúde Pública/métodos , Antibacterianos/farmacologia , Gestão de Antimicrobianos/estatística & dados numéricos , Ensaios Clínicos como Assunto , Humanos , Estudos Prospectivos , Saúde Pública/estatística & dados numéricos
7.
Dis Colon Rectum ; 60(2): 228-239, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28059920

RESUMO

BACKGROUND: Recent evidence shows that the majority of rectal cancers demonstrate occult tumor scatter after neoadjuvant chemoradiotherapy that can extend for several centimeters under adjacent normal-appearing mucosa beside the residual mucosal abnormality or scar. OBJECTIVE: This systematic review aimed to determine all of the published selection criteria and technical descriptions for local excision to date with regard to this phenomenon. DATA SOURCES: PubMed, MEDLINE, and Embase were searched using the following key words: rectal cancer, local excision, radiotherapy, and neoadjuvant. STUDY SELECTION: Studies that assessed local excision of rectal cancer after neoadjuvant chemoradiotherapy were included. Duplicate series were excluded from final analysis. INTERVENTION: All of the data points were tabulated and analyzed using Microsoft Excel. MAIN OUTCOME MEASURES: Criteria for patient selection, surgical technique, clinical restaging, pathologic assessment, and indications for completion surgery were analyzed. RESULTS: After exclusions, data from 25 studies that in total evaluated local excision in 1001 patients were included. Compared with the single accepted technique of total mesorectal excision, described techniques for local excision after neoadjuvant therapy demonstrate significant variability in many critical technical issues, such as marking/tattooing original tumor margins before neoadjuvant therapy, using pretreatment tumor size/stage as exclusion criteria, and specifically stating lateral excision margins. Where detailed, the majority of local recurrences occurred in patients with clear pathological margins, yet significant variation existed for pathological assessment and reporting, with few studies detailing R status and some not reporting margin status at all. Significant variability also existed for adverse tumor features that mandated completion surgery, and, importantly, many series describe patients refusing completion surgery where indicated. LIMITATIONS: We were unable to perform meta-analysis because studies lacked sufficient methodologic homogeneity to synthesize. CONCLUSIONS: The observations from this study prompt additional study, standardization of technique, and cautious use of local excision of rectal cancer in the setting of neoadjuvant chemoradiotherapy.


Assuntos
Adenocarcinoma/cirurgia , Quimiorradioterapia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Mesentério/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Retais/cirurgia , Reto/cirurgia , Adenocarcinoma/patologia , Humanos , Margens de Excisão , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Retais/patologia
8.
Dis Colon Rectum ; 60(1): 30-42, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27926555

RESUMO

BACKGROUND: Radical surgery is associated with significant perioperative mortality in elderly and comorbid populations. Emerging data suggest for patients with a clinical complete response after neoadjuvant chemoradiotherapy that a watch-and-wait approach may provide equivalent survival and oncological outcomes. OBJECTIVE: The purpose of this study was to compare the cost-effectiveness of watch and wait and radical surgery for patients with rectal cancer after a clinical complete response following chemoradiotherapy. DESIGN: Decision analytical modeling and a Markov simulation were used to model long-term costs, quality-adjusted life-years, and cost-effectiveness after watch and wait and radical surgery. Sensitivity analysis was used to investigate the effect of uncertainty in model parameters. SETTINGS: A third-party payer perspective was adopted. PATIENTS: Patients included in the study were a 60-year-old male cohort with no comorbidities, 80-year-old male cohorts with no comorbidities, and 80-year-old male cohorts with significant comorbidities. INTERVENTIONS: Radical surgery and watch-and-wait approaches were studied. MAIN OUTCOME MEASURES: Incremental cost, effectiveness, and cost-effectiveness ratio over the entire lifetime of the hypothetical patient cohorts were measured. RESULTS: Watch and wait was more effective (60-year-old male cohort with no comorbidities = 0.63 quality-adjusted life-years (95% CI, 2.48-3.65 quality-adjusted life-years); 80-year-old male cohort with no comorbidities = 0.56 quality-adjusted life-years (95% CI, 0.52-1.59 quality-adjusted life-years); 80-year-old male cohort with significant comorbidities = 0.72 quality-adjusted life-years (95% CI, 0.34-1.76 quality-adjusted life-years)) and less costly (60-year-old male cohort with no comorbidities = $11,332.35 (95% CI, $668.50-$23,970.20); 80-year-old male cohort with no comorbidities = $8783.93 (95% CI, $2504.26-$21,900.66); 80-year-old male cohort with significant comorbidities = $10,206.01 (95% CI, $2762.014-$24,135.31)) independent of patient cohort age and comorbidity. Consequently, watch and wait was more cost-effective with a high degree of certainty (range, 69.6%-89.2%) at a threshold of $50,000/quality-adjusted life-year. LIMITATIONS: Long-term outcomes were derived from modeled cohorts. Analysis was performed for a United Kingdom third-party payer perspective, limiting generalizability to other healthcare contexts. CONCLUSIONS: Watch and wait is likely to be cost-effective compared with radical surgery. These findings strongly support the discussion of organ-preserving strategies with suitable patients.


Assuntos
Quimiorradioterapia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Terapia Neoadjuvante , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Retais/terapia , Conduta Expectante/estatística & dados numéricos , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Procedimentos Cirúrgicos do Sistema Digestório/economia , Humanos , Reembolso de Seguro de Saúde , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Retais/economia , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Indução de Remissão , Reino Unido , Conduta Expectante/economia
9.
Dis Colon Rectum ; 59(10): 925-33, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27602923

RESUMO

BACKGROUND: Pathological complete response after chemoradiotherapy for rectal cancer occurs in 10% to 30% of patients. The best method to identify such patients remains unclear. Clinical assessment of residual mucosal abnormality is considered the most accurate method. In our institution, magnetic resonance tumor regression grade is performed as routine to assess response. OBJECTIVE: The purpose of this study was to compare the sensitivity of magnetic tumor regression grade against residual mucosal abnormality in detecting patients with a pathological complete response. DESIGN: Magnetic tumor regression grade scores from reported posttreatment MRI scans were documented. Magnetic tumor regression grade 1 to 3 was defined as likely to predict complete or near complete response. Gross appearances of the mucosa were derived from histopathology reports and used as a surrogate for clinical assessment (previously validated). Final histopathological staging was used to determine response. SETTINGS: The study was conducted at Royal Marsden National Health Service Trust, United Kingdom. PATIENTS: A total of 143 patients with rectal adenocarcinoma, diagnosed between September 1, 2009, and September 1, 2013, who received neoadjuvant chemoradiotherapy before curative surgery were included. MAIN OUTCOME MEASURES: The sensitivity of magnetic tumor regression grade and residual mucosal abnormality in detecting patients with pathological complete response were measured RESULTS: : Eighteen patients had a pathological complete response. Seventeen were detected using magnetic resonance tumor regression grade 1 to 3, with sensitivity 94% (95% CI, 0.74-0.99), and 10 were detected using residual mucosal abnormality, with sensitivity 62% (95% CI, 0.38-0.81). There was no statistical difference between the false positive rates for either method. Magnetic tumor regression grade identified 10 times more patients with a pathological complete response (diagnostic OR = 10.2 (95% CI, 1.30-73.73)) compared with clinical assessment with RMA. LIMITATIONS: Residual mucosal abnormality was used as a surrogate marker for endoscopic appearances. CONCLUSIONS: Most patients with rectal cancer who have a pathological complete response do not manifest a complete response at the mucosal level. Magnetic tumor regression grade is able to identify 10 times more patients than clinical assessment, with no significant compromise in the false positive rate.


Assuntos
Adenocarcinoma , Quimiorradioterapia/métodos , Mucosa Intestinal , Imageamento por Ressonância Magnética/métodos , Neoplasia Residual/diagnóstico , Neoplasias Retais , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Biópsia/métodos , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Projetos de Pesquisa
10.
Cereb Cortex ; 25(4): 1020-31, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24122136

RESUMO

Neurons, even in the earliest sensory areas of cortex, are subject to a great deal of contextual influence from both within and across modality connections. In the present work, we investigated whether the earliest regions of somatosensory cortex (S1 and S2) would contain content-specific information about visual object categories. We reasoned that this might be possible due to the associations formed through experience that link different sensory aspects of a given object. Participants were presented with visual images of different object categories in 2 fMRI experiments. Multivariate pattern analysis revealed reliable decoding of familiar visual object category in bilateral S1 (i.e., postcentral gyri) and right S2. We further show that this decoding is observed for familiar but not unfamiliar visual objects in S1. In addition, whole-brain searchlight decoding analyses revealed several areas in the parietal lobe that could mediate the observed context effects between vision and somatosensation. These results demonstrate that even the first cortical stages of somatosensory processing carry information about the category of visually presented familiar objects.


Assuntos
Imageamento por Ressonância Magnética/métodos , Reconhecimento Visual de Modelos/fisiologia , Processamento de Sinais Assistido por Computador , Córtex Somatossensorial/fisiologia , Mapeamento Encefálico , Discriminação Psicológica/fisiologia , Feminino , Humanos , Masculino , Análise Multivariada , Testes Neuropsicológicos
11.
Dis Colon Rectum ; 58(2): 159-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25585073

RESUMO

BACKGROUND: In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe. OBJECTIVE: This study aimed to determine whether patient age and comorbidity should influence surgeon and patient decision making where a complete clinical response is obtained. DESIGN: Decision-analytic modeling consisting of a decision tree and Markov chain simulation was used. Modeled outcome parameters were elicited both from comprehensive literature review and from a national patient outcomes database. SETTINGS: Outcomes for 3 patient cohorts treated with neoadjuvant therapy were modeled after either surgery or watch and wait. PATIENTS: Patients included 60-year-old and 80-year-old men with mild comorbidities (Charlson score <3) and 80-year-old men with significant comorbidities (Charlson score >3). MAIN OUTCOME MEASURES: Absolute survival, disease-free survival, and quality-adjusted life years were measured. RESULTS: The model found that absolute survival was similar in 60-year-old patients but was significantly improved in fit and comorbid 80-year-old patients at 1 year after treatment where watch and wait was implemented instead of radical surgery, with a survival advantage of 10.1% (95% CI, 7.9-12.6) and 13.5% (95% CI, 10.2-16.9). At all of the other time points, absolute survival was equivalent for both techniques. There were no short- or long-term differences among any patient groups managed either by radical surgery or watch and wait in terms of either disease-free survival or quality-adjusted life years. LIMITATIONS: Oncologic data for the watch-and-wait approach used for this study is derived from only a small number of studies pertaining to a highly selected group of patients. The 90-day postoperative mortality rate derived from the United Kingdom population-based study might be lower in other countries or individual institutions. CONCLUSIONS: This study suggests competing effects of oncologic and surgical risk when using watch-and-wait management and that elderly and comorbid patients have the most to gain from this approach.


Assuntos
Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Radioterapia/métodos , Neoplasias Retais/terapia , Reto/cirurgia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Simulação por Computador , Técnicas de Apoio para a Decisão , Intervalo Livre de Doença , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Neoplasias Retais/mortalidade
12.
Dis Colon Rectum ; 57(3): 311-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24509452

RESUMO

BACKGROUND: Published criteria define specific mucosal features of clinical complete response for rectal cancer after neoadjuvant chemoradiotherapy. OBJECTIVE: The aim of this study was to determine the performance of these criteria to identify a pathological complete response. DESIGN: Histopathology reports were retrieved for consecutive rectal cancers treated with neoadjuvant therapy followed by proctectomy. The mucosal appearance of residual disease was compared with the final pathological stage. SETTING: This study was conducted at a single-institution, tertiary referral center. PATIENTS: The study included 238 patients. INTERVENTIONS: All patients underwent neoadjuvant chemoradiation followed by proctectomy between 1997 and 2007. MAIN OUTCOME MEASURES: Gross mucosal appearance was compared with the final pathological stage. RESULTS: Following neoadjuvant chemoradiation, 61 of 238 (25%) patients were downstaged to ypT0. Forty-five of these 61 patients (74%) had a residual mucosal abnormality that precluded assignment of a complete response. Of these, 40 had residual ulcers (up to 10 mm in depth) and 5 had exophytic lesions. The remaining 16 patients with pathological complete response fulfilled criteria for clinical complete response and had either no visible abnormality or a scar. Although mucosal complete clinical response was statistically associated with ypT0 status (p < 0.0001), 6 of 22 (27%) patients with mucosal complete clinical response still had residual disease. Smaller size of residual mucosal abnormality was also associated with ypT0 status (p = 0.002). LIMITATIONS: This is a retrospective study and preoperative clinical assessment of response is not recorded for comparison to resected specimens. CONCLUSIONS: The majority of patients attaining ypT0 status do not display mucosal features of complete response. When present, a mucosal complete response is statistically associated with ypT0 status, but is poorly sensitive. If rectal conservation after chemoradiation is to be pursued, alternative means of restaging are required to maximize the number who might benefit from this approach.


Assuntos
Adenocarcinoma/terapia , Quimiorradioterapia , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
13.
J Surg Oncol ; 109(8): 853-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24862927

RESUMO

BACKGROUND: The main tenets of local excision of rectal cancer following neoadjuvant chemoradiation (CRT) are that the mucosal scar represents the main focus of residual disease and a solid conglomerate around this rather than being scattered (fragmented) through the bowel wall. METHODS: Retrospective review of a prospective cohort of patients with residual rectal ycT1-2N0 adenocarcinoma with small residual tumors (≤3 cm) following CRT who underwent transanal endoscopic microsurgery (TEM) with 1-cm margins around the residual mucosal abnormality was performed. Distribution and morphology (solid vs. fragmented) of tumor spread were studied and correlated to postoperative oncological outcomes. RESULTS: Thirty patients were included. Twenty percent (n = 6) were ypT1, 60% (n = 18) were ypT2, and 20% (n = 6) were ypT3 tumors. Fragmentation was present in 37%. The mean distance between foci of residual scattered tumor was 3.6 ± 2.0 mm. Lateral spread under normal mucosa was present in 19 specimens (53%; mean extension 4.8 ± 2.4 mm). With a median follow up of 32 months, none of these findings impacted upon development of recurrence. CONCLUSIONS: Both occult lateral spread and fragmented tumor patterns are common findings after CRT. Despite the potential of occult spread to mislead surgeon choice of resection margin, its presence did not influence oncological outcome in this series.


Assuntos
Adenocarcinoma/patologia , Quimiorradioterapia/efeitos adversos , Microcirurgia/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasia Residual/patologia , Neoplasias Retais/patologia , Adenocarcinoma/terapia , Canal Anal/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasia Residual/terapia , Prognóstico , Estudos Prospectivos , Neoplasias Retais/terapia , Estudos Retrospectivos
14.
Neuropsychologia ; 199: 108900, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38697558

RESUMO

Whilst previous research has linked attenuation of the mu rhythm to the observation of specific visual categories, and even to a potential role in action observation via a putative mirror neuron system, much of this work has not considered what specific type of information might be coded in this oscillatory response when triggered via vision. Here, we sought to determine whether the mu rhythm contains content-specific information about the identity of familiar (and also unfamiliar) graspable objects. In the present study, right-handed participants (N = 27) viewed images of both familiar (apple, wine glass) and unfamiliar (cubie, smoothie) graspable objects, whilst performing an orthogonal task at fixation. Multivariate pattern analysis (MVPA) revealed significant decoding of familiar, but not unfamiliar, visual object categories in the mu rhythm response. Thus, simply viewing familiar graspable objects may automatically trigger activation of associated tactile and/or motor properties in sensorimotor areas, reflected in the mu rhythm. In addition, we report significant attenuation in the central beta band for both familiar and unfamiliar visual objects, but not in the mu rhythm. Our findings highlight how analysing two different aspects of the oscillatory response - either attenuation or the representation of information content - provide complementary views on the role of the mu rhythm in response to viewing graspable object categories.


Assuntos
Reconhecimento Psicológico , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Reconhecimento Psicológico/fisiologia , Ondas Encefálicas/fisiologia , Eletroencefalografia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa
15.
J Chromatogr A ; 1713: 464522, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38041975

RESUMO

Microsampling allows the collection of blood samples using a method which is inexpensive, simple and minimally-invasive, without the need for specially-trained medical staff. Analysis of whole blood provides a more holistic understanding of per- and polyfluoroalkyl substances (PFAS) body burden. Capillary action microsamplers (Trajan hemaPEN®) allow the controlled collection of whole blood as dried blood spots (DBS) (four 2.74 µL ± 5 %). The quantification of 75 PFAS from DBS was evaluated by comparing five common extraction techniques. Spiked blood (5 ng/mL PFAS) was extracted by protein precipitation (centrifuged; filtered), acid-base liquid-liquid extraction, trypsin protease digestion, and weak anion exchange (WAX) solid-phase extraction with analysis by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Filtered protein precipitation was the most effective extraction method, recovering 72 of the 75 PFAS within 70 to 130 % with method reporting limit (MRL) for PFOS of 0.17 ng/L and ranging between 0.05 ng/mL and 0.34 ng/mL for all other PFAS. The optimised method was applied to human blood samples to examine Inter- (n = 7) and intra-day (n = 5) PFAS blood levels in one individual. Sixteen PFAS were detected with an overall Σ16PFAS mean = 6.3 (range = 5.7-7.0) ng/mL and perfluorooctane sulfonate (branched and linear isomers, ΣPFOS) = 3.3 (2.8-3.7) ng/mL being the dominant PFAS present. To the authors knowledge, this minimally invasive self-sampling protocol is the most extensive method for PFAS in blood reported and could be a useful tool for large scale human biomonitoring studies.


Assuntos
Fluorocarbonos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Teste em Amostras de Sangue Seco/métodos , Cromatografia Líquida de Alta Pressão/métodos
16.
Sci Rep ; 14(1): 9402, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658575

RESUMO

Perceptual decisions are derived from the combination of priors and sensorial input. While priors are broadly understood to reflect experience/expertise developed over one's lifetime, the role of perceptual expertise at the individual level has seldom been directly explored. Here, we manipulate probabilistic information associated with a high and low expertise category (faces and cars respectively), while assessing individual level of expertise with each category. 67 participants learned the probabilistic association between a color cue and each target category (face/car) in a behavioural categorization task. Neural activity (EEG) was then recorded in a similar paradigm in the same participants featuring the previously learned contingencies without the explicit task. Behaviourally, perception of the higher expertise category (faces) was modulated by expectation. Specifically, we observed facilitatory and interference effects when targets were correctly or incorrectly expected, which were also associated with independently measured individual levels of face expertise. Multivariate pattern analysis of the EEG signal revealed clear effects of expectation from 100 ms post stimulus, with significant decoding of the neural response to expected vs. not stimuli, when viewing identical images. Latency of peak decoding when participants saw faces was directly associated with individual level facilitation effects in the behavioural task. The current results not only provide time sensitive evidence of expectation effects on early perception but highlight the role of higher-level expertise on forming priors.


Assuntos
Eletroencefalografia , Reconhecimento Facial , Humanos , Masculino , Feminino , Adulto , Reconhecimento Facial/fisiologia , Adulto Jovem , Estimulação Luminosa , Tempo de Reação/fisiologia , Percepção Visual/fisiologia , Face/fisiologia
17.
Eur J Neurosci ; 37(7): 1130-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23373719

RESUMO

Higher visual areas in the occipitotemporal cortex contain discrete regions for face processing, but it remains unclear if V1 is modulated by top-down influences during face discrimination, and if this is widespread throughout V1 or localized to retinotopic regions processing task-relevant facial features. Employing functional magnetic resonance imaging (fMRI), we mapped the cortical representation of two feature locations that modulate higher visual areas during categorical judgements - the eyes and mouth. Subjects were presented with happy and fearful faces, and we measured the fMRI signal of V1 regions processing the eyes and mouth whilst subjects engaged in gender and expression categorization tasks. In a univariate analysis, we used a region-of-interest-based general linear model approach to reveal changes in activation within these regions as a function of task. We then trained a linear pattern classifier to classify facial expression or gender on the basis of V1 data from 'eye' and 'mouth' regions, and from the remaining non-diagnostic V1 region. Using multivariate techniques, we show that V1 activity discriminates face categories both in local 'diagnostic' and widespread 'non-diagnostic' cortical subregions. This indicates that V1 might receive the processed outcome of complex facial feature analysis from other cortical (i.e. fusiform face area, occipital face area) or subcortical areas (amygdala).


Assuntos
Expressão Facial , Percepção de Forma , Córtex Visual/fisiologia , Adulto , Mapeamento Encefálico , Olho , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Boca
18.
Proc Natl Acad Sci U S A ; 107(46): 20099-103, 2010 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-21041652

RESUMO

Even within the early sensory areas, the majority of the input to any given cortical neuron comes from other cortical neurons. To extend our knowledge of the contextual information that is transmitted by such lateral and feedback connections, we investigated how visually nonstimulated regions in primary visual cortex (V1) and visual area V2 are influenced by the surrounding context. We used functional magnetic resonance imaging (fMRI) and pattern-classification methods to show that the cortical representation of a nonstimulated quarter-field carries information that can discriminate the surrounding visual context. We show further that the activity patterns in these regions are significantly related to those observed with feed-forward stimulation and that these effects are driven primarily by V1. These results thus demonstrate that visual context strongly influences early visual areas even in the absence of differential feed-forward thalamic stimulation.


Assuntos
Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Córtex Visual/fisiologia , Algoritmos , Mapeamento Encefálico , Análise Discriminante , Humanos
19.
Behav Brain Sci ; 36(3): 221, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23663531

RESUMO

Clark offers a powerful description of the brain as a prediction machine, which offers progress on two distinct levels. First, on an abstract conceptual level, it provides a unifying framework for perception, action, and cognition (including subdivisions such as attention, expectation, and imagination). Second, hierarchical prediction offers progress on a concrete descriptive level for testing and constraining conceptual elements and mechanisms of predictive coding models (estimation of predictions, prediction errors, and internal models).


Assuntos
Atenção/fisiologia , Encéfalo/fisiologia , Cognição/fisiologia , Ciência Cognitiva/tendências , Percepção/fisiologia , Humanos
20.
Biology (Basel) ; 12(7)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37508451

RESUMO

Neurons in the primary visual cortex (V1) receive sensory inputs that describe small, local regions of the visual scene and cortical feedback inputs from higher visual areas processing the global scene context. Investigating the spatial precision of this visual contextual modulation will contribute to our understanding of the functional role of cortical feedback inputs in perceptual computations. We used human functional magnetic resonance imaging (fMRI) to test the spatial precision of contextual feedback inputs to V1 during natural scene processing. We measured brain activity patterns in the stimulated regions of V1 and in regions that we blocked from direct feedforward input, receiving information only from non-feedforward (i.e., feedback and lateral) inputs. We measured the spatial precision of contextual feedback signals by generalising brain activity patterns across parametrically spatially displaced versions of identical images using an MVPA cross-classification approach. We found that fMRI activity patterns in cortical feedback signals predicted our scene-specific features in V1 with a precision of approximately 4 degrees. The stimulated regions of V1 carried more precise scene information than non-stimulated regions; however, these regions also contained information patterns that generalised up to 4 degrees. This result shows that contextual signals relating to the global scene are similarly fed back to V1 when feedforward inputs are either present or absent. Our results are in line with contextual feedback signals from extrastriate areas to V1, describing global scene information and contributing to perceptual computations such as the hierarchical representation of feature boundaries within natural scenes.

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