•This Clinical Practice Guideline provides key recommendations on the management of soft tissue and visceral sarcomas.•Recommendations have been agreed following a consensus meeting of ...representatives from ESMO, EURACAN and GENTURIS.•Authorship includes a multidisciplinary group of experts from several European institutions, India and Japan.
Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with ...cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival.
We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years.
A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval CI, 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively.
The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).
Estimates of objectively measured physical activity among older adults differ depending on the cut points used to define intensity. Our objective was to assess 1) moderate to vigorous physical ...activity (MVPA), exploring differences in prevalence depending on the cut point used, and 2) sedentary behavior, among US adults aged 60 years or older.
We used the most recently available accelerometer data (2003-2004 and 2005-2006) from the National Health and Nutrition Examination Survey. The sample included 2,630 adults aged 60 or older who wore an ActiGraph accelerometer for 1 week. We defined MVPA using 4 cut points (≥500, ≥1,000, ≥1,500, and ≥2,000 counts/min) and sedentary behavior as fewer than 100 counts per minute. All estimates were weighted to reflect the US population.
The overall average counts per minute was 216. Mean MVPA ranged from 10.8 minutes per day (based on 2,000 counts/min) to 106.8 minutes per day (based on 500 counts/min). Regardless of the cut point used, MVPA was lower with each successive age group (60-69, 70-79, and ≥80) and higher among men than women. At any cut point, MVPA was highest for Hispanics and "other" racial/ethnic groups, followed by non-Hispanic whites and non-Hispanic blacks. The average time spent in sedentary behavior was 8.5 hours per day. The amount of sedentary time was greater among participants who were aged 80 or older compared to younger groups and among men compared to women.
MVPA estimates vary among adults aged 60 or older, depending on the cut point chosen, and most of their time is spent in sedentary behaviors. These considerations and the data presented suggest more research is necessary to identify the appropriate method of setting accelerometer cut points for MVPA in older adults.
•This Clinical Practice Guideline provides key recommendations on the management of bone sarcomas.•Recommendations have been agreed following a consensus meeting of representatives from ESMO, ...EURACAN, GENTURIS and ERNPaedCan.•Authorship includes a multidisciplinary group of experts from different institutions and countries worldwide.
The spatial sensitivity of the human visual system depends on stimulus color: achromatic gratings can be resolved at relatively high spatial frequencies while sensitivity to isoluminant color ...contrast tends to be more low-pass. Models of early spatial vision often assume that the receptive field size of pattern-sensitive neurons is correlated with their spatial frequency sensitivity - larger receptive fields are typically associated with lower optimal spatial frequency. A strong prediction of this model is that neurons coding isoluminant chromatic patterns should have, on average, a larger receptive field size than neurons sensitive to achromatic patterns. Here, we test this assumption using functional magnetic resonance imaging (fMRI). We show that while spatial frequency sensitivity depends on chromaticity in the manner predicted by behavioral measurements, population receptive field (pRF) size measurements show no such dependency. At any given eccentricity, the mean pRF size for neuronal populations driven by luminance, opponent red/green and S-cone isolating contrast, are identical. Changes in pRF size (for example, an increase with eccentricity and visual area hierarchy) are also identical across the three chromatic conditions. These results suggest that fMRI measurements of receptive field size and spatial resolution can be decoupled under some circumstances - potentially reflecting a fundamental dissociation between these parameters at the level of neuronal populations.
•Novel use of fMRI population receptive field (pRF) mapping, using chromatic stimuli.•Spatial frequency sensitivity in early visual areas measured with fMRI.•Differences in spatial sensitivity found between S-cone and luminance conditions.•No significant differences in pRF sizes between S-cone and luminance conditions.•Suggests that pRF sizes and spatial resolution are not coupled.
Even after conventional patching treatment, individuals with a history of amblyopia typically lack good stereo vision. This is often attributed to atypical suppression between the eyes, yet the ...specific mechanism is still unclear. Guided by computational models of binocular vision, we tested explicit predictions about how neural responses to contrast might differ in individuals with impaired binocular vision. Participants with a history of amblyopia (N = 25), and control participants with typical visual development (N = 19) took part in the study. Neural responses to different combinations of contrast in the left and right eyes, were measured using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Stimuli were sinusoidal gratings with a spatial frequency of 3c/deg, flickering at 4 Hz. In the fMRI experiment, we also ran population receptive field and retinotopic mapping sequences, and a phase-encoded localiser stimulus, to identify voxels in primary visual cortex (V1) sensitive to the main stimulus. Neural responses in both modalities increased monotonically with stimulus contrast. When measured with EEG, responses were attenuated in the weaker eye, consistent with a fixed tonic suppression of that eye. When measured with fMRI, a low contrast stimulus in the weaker eye substantially reduced the response to a high contrast stimulus in the stronger eye. This effect was stronger than when the stimulus-eye pairings were reversed, consistent with unbalanced dynamic suppression between the eyes. Measuring neural responses using different methods leads to different conclusions about visual differences in individuals with impaired binocular vision. Both of the atypical suppression effects may relate to binocular perceptual deficits, e.g. in stereopsis, and we anticipate that these measures could be informative for monitoring the progress of treatments aimed at recovering binocular vision.
Seminal work in the early nineties revealed that the visual receptive field of neurons in cat primary visual cortex can change in location and size when artificial scotomas are applied. Recent work ...now suggests that these single neuron receptive field dynamics also pertain to the neuronal population receptive field (pRF) that can be measured in humans with functional magnetic resonance imaging (fMRI). To examine this further, we estimated the pRF in twelve healthy participants while masking the central portion of the visual field. We found that the pRF changes in location and size for two differently sized artificial scotomas, and that these pRF dynamics are most likely due to a combination of the neuronal receptive field position and size scatter as well as modulatory feedback signals from extrastriate visual areas.
Symmetry is effortlessly perceived by humans across changes in viewing geometry. Here, we re‐examined the network subserving symmetry processing in the context of up‐to‐date retinotopic definitions ...of visual areas. Responses in object selective cortex, as defined by functional localizers, were also examined. We further examined responses to both frontoparallel and slanted symmetry while manipulating attention both toward and away from symmetry. Symmetry‐specific responses first emerge in V3 and continue across all downstream areas examined. Of the retinotopic areas, ventral occipital VO1 showed the strongest symmetry response, which was similar in magnitude to the responses observed in object selective cortex. Neural responses were found to increase with both the coherence and folds of symmetry. Compared to passive viewing, drawing attention to symmetry generally increased neural responses and the correspondence of these neural responses with psychophysical performance. Examining symmetry on the slanted plane found responses to again emerge in V3, continue through downstream visual cortex, and be strongest in VO1 and LOB. Both slanted and frontoparallel symmetry evoked similar activity when participants performed a symmetry‐related task. However, when a symmetry‐unrelated task was performed, fMRI responses to slanted symmetry were reduced relative to their frontoparallel counterparts. These task‐related changes provide a neural signature that suggests slant has to be computed ahead of symmetry being appropriately extracted, known as the “normalization” account of symmetry processing. Specifically, our results suggest that normalization occurs naturally when attention is directed toward symmetry and orientation, but becomes interrupted when attention is directed away from these features.
In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are ...plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1–V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere.
•DWI confirms asymmetric optic nerve projection in a patient with chiasma hypoplasia.•pRF mapping reveals superposition of 3 hemifield representations in left hemisphere.•Triple maps highlight scope of plasticity in congenital visual system abnormalities.
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