Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy.

Purpose: In stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. Methods: A retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. Results: All treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (-46.1 %) and 1.3 min (-56.2 %) for 6 and 10 MV FFF respectively. Conclusions: The high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Naturalistic Object Representations Depend on Distance and Size Cues.

Egocentric distance and real-world size are important cues for object perception and action. Nevertheless, most studies of human vision rely on two-dimensional pictorial stimuli that convey ambiguous distance and size information. Here, we use fMRI to test whether pictures are represented differently in the human brain from real, tangible objects that convey unambiguous distance and size cues. Participants directly viewed stimuli in two display formats (real objects and matched printed pictures of those objects) presented at different egocentric distances (near and far). We measured the effects of format and distance on fMRI response amplitudes and response patterns. We found that fMRI response amplitudes in the lateral occipital and posterior parietal cortices were stronger overall for real objects than for pictures. In these areas and many others, including regions involved in action guidance, responses to real objects were stronger for near vs. far stimuli, whereas distance had little effect on responses to pictures-suggesting that distance determines relevance to action for real objects, but not for pictures. Although stimulus distance especially influenced response patterns in dorsal areas that operate in the service of visually guided action, distance also modulated representations in ventral cortex, where object responses are thought to remain invariant across contextual changes. We observed object size representations for both stimulus formats in ventral cortex but predominantly only for real objects in dorsal cortex. Together, these results demonstrate that whether brain responses reflect physical object characteristics depends on whether the experimental stimuli convey unambiguous information about those characteristics. Significance Statement: Classic frameworks of vision attribute perception of inherent object characteristics, such as size, to the ventral visual pathway, and processing of spatial characteristics relevant to action, such as distance, to the dorsal visual pathway. However, these frameworks are based on studies that used projected images of objects whose actual size and distance from the observer were ambiguous. Here, we find that when object size and distance information in the stimulus is less ambiguous, these characteristics are widely represented in both visual pathways. Our results provide valuable new insights into the brain representations of objects and their various physical attributes in the context of naturalistic vision.

Environmental influences on induction of itching and scratching using immersive virtual reality.

Chronic itching is a serious and uncomfortable condition. The scratch response might result in a vicious cycle of alternating itching and scratching. To develop psychological interventions for people suffering from chronic itching and to break the vicious itch-scratching-itch cycle, it is important to elucidate which environmental factors trigger itch sensations. Virtual reality (VR) techniques provide a useful tool to examine specific content characteristics in a three-dimensional (3D VR) environment and their influences on itch sensations and scratching behaviour. This article describes two experiments in which we focused on the effects of environmental information on itching and scratching behaviour. Additionally, in the second experiment, we examined the influence of having a chronic skin condition on sensitivity to itch induction. We found evidence for the importance of the content of audio-visual materials for the effectiveness in inducing feelings of itch in the observers. In both experiments, we observed significantly higher levels of perceived itch in the itch-inducing conditions than in the control condition. Moreover, the results showed that elevated levels of perceived itch were associated with an increase in scratching behaviours, which was especially salient in the contagious itch condition, in which perceived itch was accompanied by a significant increase in the number of scratches. Experiment 2 additionally showed increased perceived itch levels in participants who reported having a chronic skin condition, reflecting higher sensitivity to itch-inducing audio-visual stimuli in this group than in participants without a chronic skin condition. Based on the results we concluded that directing attention towards itch- or scratch aspects of related information in the environment and to the consequences for one's own skin are effective tools to induce itch sensations and scratching behaviour. This knowledge provides tools for developing novel strategies in advising and treating people suffering from chronic itching and breaking the vicious itch-scratching-itch cycle.

Full-Dose Intraoperative Electron Radiotherapy for Early Breast Cancer: Evidence from a Single Center's Experience.

To evaluate the clinical response rate and cosmetic outcome after full-dose intraoperative electron radiotherapy (IOERT) in early breast cancer (BC) treated with conserving surgery. Inclusion criteria were: >60 years old, clinical tumor size ≤2 cm, luminal A carcinoma, patological negative lymph nodes, excluded lobular carcinoma histology. IOERT was delivered with a dose of 21 Gy at 90% isodose. Clinical, cosmetic and/or instrumental follow-up were performed 45 days after IOERT, 6 months after the first check, and every 12 months thereafter. Acute and late toxicities were assessed with the CTCAE v.4.03 and EORTC-RTOG scales, respectively. Cosmetic outcome was evaluated using the Harvard/NSABO/RTOG Breast Cosmesis Grading Scale. Overall, 162 consecutive patients were included in this analysis (median follow-up: 54 months, range: 1-98 months). The overall response rate was 97.5% (CI 95%: 0.93-0.99%). Locoragional relapse occurred in 2.5% of patients. No patient showed distant metastases. No patient showed radiation-related acute complications, with 3.7% showing late G2-3 toxicity. Only 3.7% of patients showed poor cosmetic results. Our data confirmed that IOERT is a feasible and valid therapeutic option in low-risk BC patients treated with lumpectomy. A low local recurrence rate combined with good cosmetic results validates the settings of our operative method in routinely clinical practice.

Dosimetric characterization of a mobile accelerator dedicated for intraoperative radiation therapy: Monte Carlo simulations and experimental validation.

PURPOSE: This Technical Note validates previously published data about the dosimetry of the electron beams produced by a mobile accelerator dedicated for intraoperative radiation therapy (IORT). The evaluation of the directional response of a PTW microDiamond detector is presented together with a detailed analysis of the output factors (OFs) for bevelled applicators. METHODS: The OFs of the 6, 8, 10 and 12 MeV electron beams produced by a light intraoperative accelerator (LIAC, SIT, Italy) were measured in a commercial water phantom using the microDiamond. A set of flat and bevelled applicators with sizes ranging from 4 to 10 cm was characterized. For bevelled applicators, a correction for the angular dependence of the microDiamond was calculated using a home-made spherical phantom. Correction factors were obtained through measurements performed rotating the accelerator treatment head at 0°, 15°, 30° and 45°. RESULTS: For flat applicators, the average deviation between measured and simulated OFs was (-1.1 ± 0.7)%. The microDiamond showed a higher angular dependence for the 6 MeV beam (∼8% for angles up to 45°, range 92 % ÷ 100 %), while the variations for 8, 10 and 12 MeV beams were âˆ¼ 4 % (range 97 % ÷ 101 %). Correcting for this dependence, the average deviation of the OFs for bevelled applicators was (-0.9 ± 1.6)%. CONCLUSIONS: The presented results were in very good agreement with those reported in literature. Very similar deviations were found between flat and bevelled applicators confirming the suitability of our method to determine the angular dependence correction factors of the microDiamond detector.

"My Life during the Lockdown": Emotional Experiences of European Adolescents during the COVID-19 Crisis.

This study investigates, using an online self-report questionnaire, adolescents' emotional reactions during the lockdown in a sample of 2105 secondary school students (aged 14-19) in Italy, Romania, and Croatia. We used a self-reported online questionnaire (answers on a 5-point scale or binary), composed of 73 questions investigating the opinions, feelings, and emotions of teenagers, along with sociodemographic information and measures of the exposure to lockdown. The survey was conducted online through a web platform in Italy (between 27 April and 15 June 2020), Romania, and Croatia (3 June and 2 July 2020). Students aged >14 years, living in a small flat, and not spending time outside were more likely to report anger, sadness, boredom/emptiness, and anxiety. Boys were significantly less likely than girls to report all measured emotional reactions. Those who lost someone from COVID-19 were more than twice as likely to experience anger compared to those who did not. Our findings may help identifying adolescents more likely to report negative emotional reactions during the COVID-19 pandemic and inform public health strategies for improving mental health among adolescents during/after the COVID-19 crisis.

Object responses are highly malleable, rather than invariant, with changes in object appearance.

Theoretical frameworks of human vision argue that object responses remain stable, or 'invariant', despite changes in viewing conditions that can alter object appearance but not identity. Here, in a major departure from previous approaches that have relied on two-dimensional (2-D) images to study object processing, we demonstrate that changes in an object's appearance, but not its identity, can lead to striking shifts in behavioral responses to objects. We used inverse multidimensional scaling (MDS) to measure the extent to which arrangements of objects in a sorting task were similar or different when the stimuli were displayed as scaled 2-D images, three-dimensional (3-D) augmented reality (AR) projections, or real-world solids. We were especially interested in whether sorting behavior in each display format was based on conceptual (e.g., typical location) versus physical object characteristics. We found that 2-D images of objects were arranged according to conceptual (typical location), but not physical, properties. AR projections, conversely, were arranged primarily according to physical properties such as real-world size, elongation and weight, but not conceptual properties. Real-world solid objects, unlike both 2-D and 3-D images, were arranged using multidimensional criteria that incorporated both conceptual and physical object characteristics. Our results suggest that object responses can be strikingly malleable, rather than invariant, with changes in the visual characteristics of the stimulus. The findings raise important questions about limits of invariance in object processing, and underscore the importance of studying responses to richer stimuli that more closely resemble those we encounter in real-world environments.

Directional tuning for eye and arm movements in overlapping regions in human posterior parietal cortex.

A network of frontal and parietal regions is known to be recruited during the planning and execution of arm and eye movements. While movements of the two effectors are typically coupled with each other, it remains unresolved how information is shared between them. Here we aimed to identify regions containing neuronal populations that show directional tuning for both arm and eye movements. In two separate fMRI experiments, the same participants were scanned while performing a center-out arm or eye movement task. Using a whole-brain searchlight-based representational similarity analysis (RSA), we found that a bilateral region in the posterior superior parietal lobule represents both arm and eye movement direction, thus extending previous findings in monkeys.

Flexible Visuomotor Associations in Touchscreen Control.

To move real objects, our hand needs to get in direct physical contact with the object. However, this is not necessarily the case when interacting with virtual objects, for example when displacing objects on tablets by swipe movements. Here, we performed two experiments to study the behavioral strategies of these movements, examining how visual information about the virtual object is mapped into a swipe that moves the object into a goal location. In the first experiment, we investigated how swiping behavior depends on whether objects were located within or outside the swiping workspace. Results show that participants do not start the swipe movement by placing their finger on the virtual object, as they do when reaching to real objects, but rather keep a systematic distance between the object location and the initial swipe location. This mismatch, which was experimentally imposed by placing the object outside the workspace, also occurred when the object was within the workspace. In the second experiment, we investigated which factors determine this mismatch by systematically manipulating the initial hand location, the location of the object and the location of the goal. Dimensionality reduction of the data showed that three factors are taken into account when participants choose the initial swipe location: the expected total movement distance, the distance between their finger on the screen and the object, and a preference not to cover the object. The weight given to each factor differed among individuals. These results delineate, for the first time, the flexibility of visuomotor associations in the virtual world.

Disentangling Representations of Object and Grasp Properties in the Human Brain.

UNLABELLED: The properties of objects, such as shape, influence the way we grasp them. To quantify the role of different brain regions during grasping, it is necessary to disentangle the processing of visual dimensions related to object properties from the motor aspects related to the specific hand configuration. We orthogonally varied object properties (shape, size, and elongation) and task (passive viewing, precision grip with two or five digits, or coarse grip with five digits) and used representational similarity analysis of functional magnetic resonance imaging data to infer the representation of object properties and hand configuration in the human brain. We found that object elongation is the most strongly represented object feature during grasping and is coded preferentially in the primary visual cortex as well as the anterior and posterior superior-parieto-occipital cortex. By contrast, primary somatosensory, motor, and ventral premotor cortices coded preferentially the number of digits while ventral-stream and dorsal-stream regions coded a mix of visual and motor dimensions. The representation of object features varied with task modality, as object elongation was less relevant during passive viewing than grasping. To summarize, this study shows that elongation is a particularly relevant property of the object to grasp, which along with the number of digits used, is represented within both ventral-stream and parietal regions, suggesting that communication between the two streams about these specific visual and motor dimensions might be relevant to the execution of efficient grasping actions. SIGNIFICANCE STATEMENT: To grasp something, the visual properties of an object guide preshaping of the hand into the appropriate configuration. Different grips can be used, and different objects require different hand configurations. However, in natural actions, grip and object type are often confounded, and the few experiments that have attempted to separate them have produced conflicting results. As such, it is unclear how visual and motor properties are represented across brain regions during grasping. Here we orthogonally manipulated object properties and grip, and revealed the visual dimension (object elongation) and the motor dimension (number of digits) that are more strongly coded in ventral and dorsal streams. These results suggest that both streams play a role in the visuomotor coding essential for grasping.

Increased incidence of childhood leukemia in urban areas: a population-based case-control study.

OBJECTIVE: We carried out a population-based case-control study to assess the possibility of an excess risk of childhood leukemia in urban areas, independently from road traffic pollution. METHODS: Study subjects were the 111 cases of childhood leukemia diagnosed from 1998 to 2011 among residents of two provinces of the northern Italian Emilia-Romagna region, and 444 controls matched by age and sex. Through mapping of the region carried out by remote sensing, we examined the percentage of urban or rural area in the 100-meter circular buffer around each child's house. We also modeled annual average exposure to benzene and PM10 from vehicular traffic at each residence. RESULTS: In a multivariate model adjusting for benzene and PM10, the odds ratio of leukemia associated with residence in a highly urbanized area and residential area (≥95% land use of this type near the child's home) was 1.4 (95% confidence intervals 0.8-2.4) and 1.3 (0.8-2.2), respectively. An increased risk was also found in association with the proximity to «dumps, scrap yards, and building sites¼. No association emerged with residence in rural areas or near industrial plants. CONCLUSIONS: These results indicate that children living in urban areas experience an excess leukemia risk, independently from exposure to pollutants from vehicles.

Overlapping representations for grip type and reach direction.

To grasp an object, we need to move the arm toward it and assume the appropriate hand configuration. While previous studies suggested dorsomedial and dorsolateral pathways in the brain specialized respectively for the transport and grip components, more recent studies cast doubt on such a clear-cut distinction. It is unclear, however, to which degree neuronal populations selective for the two components overlap, and if so, to which degree they interact. Here, we used multivoxel pattern analysis (MVPA) of functional magnetic resonance imaging (fMRI) data to investigate the representation of three center-out movements (touch, pincer grip, whole-hand grip) performed in five reach directions. We found selectivity exclusively for reach direction in posterior and rostral superior parietal lobes (SPLp, SPLr), supplementary motor area (SMA), and the superior portion of dorsal premotor cortex (PMDs). Instead, we found selectivity for both grip type and reach direction in the inferior portion of dorsal premotor cortex (PMDi), ventral premotor cortex (PMv), anterior intraparietal sulcus (aIPS), primary motor (M1), somatosensory (S1) cortices and the anterior superior parietal lobe (SPLa). Within these regions, PMv, M1, aIPS and SPLa showed weak interactions between the transport and grip components. Our results suggest that human PMDi and S1 contain both grip- and reach-direction selective neuronal populations that retain their functional independence, whereas this information might be combined at the level of PMv, M1, aIPS, and SPLa.

Cross-modal plasticity preserves functional specialization in posterior parietal cortex.

In congenitally blind individuals, many regions of the brain that are typically heavily involved in visual processing are recruited for a variety of nonvisual sensory and cognitive tasks (Rauschecker 1995; Pascual-Leone et al. 2005). This phenomenon-cross-modal plasticity-has been widely documented, but the principles that determine where and how cross-modal changes occur remain poorly understood (Bavelier and Neville 2002). Here, we evaluate the hypothesis that cross-modal plasticity respects the type of computations performed by a region, even as it changes the modality of the inputs over which they are carried out (Pascual-Leone and Hamilton 2001). We compared the fMRI signal in sighted and congenitally blind participants during proprioceptively guided reaching. We show that parietooccipital reach-related regions retain their functional role-encoding of the spatial position of the reach target-even as the dominant modality in this region changes from visual to nonvisual inputs. This suggests that the computational role of a region, independently of the processing modality, codetermines its potential cross-modal recruitment. Our findings demonstrate that preservation of functional properties can serve as a guiding principle for cross-modal plasticity even in visuomotor cortical regions, i.e. beyond the early visual cortex and other traditional visual areas.

The role of numerosity in processing nonsymbolic proportions.

The difficulty in processing fractions seems to be related to the interference between the whole-number value of the numerator and the denominator and the real value of the fraction. Here we assess whether the reported problems with symbolic fractions extend to the nonsymbolic domain, by presenting fractions as arrays of black and white dots representing the two operands. Participants were asked to compare a target array with a reference array in two separate tasks using the same stimuli: a numerosity task comparing just the number of white dots in the two arrays; and a proportion task comparing the proportion of black and white dots. The proportion task yielded lower accuracy and slower response, confirming that even with nonsymbolic stimuli accessing proportional information is relatively difficult. However, using a congruity manipulation in which the greater numerosity of white dots could co-occur with a lower proportion of them, and vice versa, it was found that both task-irrelevant dimensions would interfere with the task-relevant dimension suggesting that both numerosity and proportion information was automatically accessed. The results indicate that the magnitude of fractions can be automatically and holistically processed in the nonsymbolic domain.

Distributed sensitivity for movement amplitude in directionally tuned neuronal populations.

Neurons in macaque primary motor cortex and dorsal premotor cortex are tuned to movement direction. In humans, neuronal populations tuned to movement direction have recently been described using multivoxel pattern analysis and functional magnetic resonance imaging adaptation. It is unclear, however, to what extent directionally tuned neuronal populations are sensitive to movement amplitude. Here we used functional magnetic resonance imaging adaptation to determine whether directionally tuned neuronal populations are modulated by movement amplitude. In different blocks, participants were adapted to small- or large-amplitude hand-reaching movements. On occasional test trials, we parametrically varied the angular difference between adaptation and test direction and the congruency between adapted and tested amplitude (same or different). We predicted that the blood oxygen level-dependent signal in directionally tuned regions should be adapted in proportion to the angular difference between adaptation and test direction. Directionally tuned regions insensitive to movement amplitude should show a transfer of adaptation from the adapted to the nonadapted amplitude. In contrast, regions sensitive to the specific combination of movement direction and amplitude should show directional tuning only for the adapted amplitude. We identified a network of parietal and frontal regions tuned to movement direction. We found that parietal areas contain neuronal populations sensitive to specific combinations of movement direction and amplitude, while frontal areas show transfer from the adapted to the nonadapted amplitude during small-amplitude movements after adaptation to large amplitude, but not vice versa. Our results thus imply different processing of movement amplitude in directionally tuned frontal and parietal areas.

Tuning curves for movement direction in the human visuomotor system.

Neurons in macaque primary motor cortex (M1) are broadly tuned to arm movement direction. Recent evidence suggests that human M1 contains directionally tuned neurons, but it is unclear which other areas are part of the network coding movement direction and what characterizes the responses of neuronal populations in those areas. Such information would be highly relevant for the implementation of brain-computer interfaces (BCIs) in paralyzed patients. We used functional magnetic resonance imaging adaptation to identify which areas of the human brain show directional selectivity and the degree to which these areas are affected by the type of motor act (to press vs to grasp). After adapting participants to one particular hand movement direction, we measured the release from adaptation during occasional test trials, parametrically varying the angular difference between adaptation and test direction. We identified multiple areas broadly tuned to movement direction, including M1, dorsal premotor cortex, intraparietal sulcus, and the parietal reach region. Within these areas, we observed a gradient of directional selectivity, with highest directional selectivity in the right parietal reach region, for both right- and left-hand movements. Moreover, directional selectivity was modulated by the type of motor act to varying degrees, with the largest effect in M1 and the smallest modulation in the parietal reach region. These data provide an important extension of our knowledge about directional tuning in the human brain. Furthermore, our results suggest that the parietal reach region might be an ideal candidate for the implementation of BCI in paralyzed patients.

The mental representation of numerical fractions: real or integer?

Numerical fractions are commonly used to express ratios and proportions (i.e., real numbers), but little is known about how they are mentally represented and processed by skilled adults. Four experiments employed comparison tasks to investigate the distance effect and the effect of the spatial numerical association of response codes (SNARC) for fractions. Results showed that fractions were processed componentially and that the real numerical value of the fraction was not accessed, indicating that processing the fraction's magnitude is not automatic. In contrast, responses were influenced by the numerical magnitude of the components and reflected the simple comparison between numerators, denominators, and reference, depending on the strategy adopted. Strategies were used even by highly skilled participants and were flexibly adapted to the specific experimental context. In line with results on the whole number bias in children, these findings suggest that the understanding of fractions is rooted in the ability to represent discrete numerosities (i.e., integers) rather than real numbers and that the well-known difficulties of children in mastering fractions are circumvented by skilled adults through a flexible use of strategies based on the integer components.