Long-Term Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy.

PURPOSE: Second malignancy is a rare but potentially lethal event after prostate brachytherapy, but data remain scarce on its long-term risk. The objective of this study is to estimate the number of pelvic second malignancies following brachytherapy compared to radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively reviewed patients treated with low-dose 125I brachytherapy and RP in British Columbia from 1999 to 2010. Kaplan-Meier estimates for pelvic (bladder and rectum), invasive pelvic, any second malignancy, and death from any second malignancy were assessed. Cox multivariable analyses were performed adjusting for initial treatment type, age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking history. RESULTS: Two thousand three hundred seventy-eight brachytherapy and 9089 RP patients were included. Median age was 66 years (interquartile range [IQR] 61-71) and 63 years (IQR 58-67), respectively. Median follow-up time to event or censured was 14 years (IQR 11.5-17.3). The Kaplan-Meier estimates for pelvic second malignancy at 15 and 20 years were 6.4% and 9.8%, respectively, after brachytherapy, and 3.2% and 4.2% after RP. Time to any second malignancy and time to death from any second malignancy were not significantly different (P > .05). On Cox multivariable analysis, brachytherapy, compared to surgery, was an independent factor for pelvic (hazard ratio [HR] 1.81 [95% CI 1.45-2.26], P < .001) and invasive pelvic second malignancy (HR 2.13 [95% CI 1.61-2.83], P < .001). Increased age and smoking were also associated with higher estimates of events (P < .001). CONCLUSIONS: After adjustment for age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking status, numerically higher long-term HRs of pelvic and invasive pelvic second malignancy in patients treated with brachytherapy compared to RP were noted.

Brain decoding of the Human Connectome Project tasks in a dense individual fMRI dataset.

Brain decoding aims to infer cognitive states from patterns of brain activity. Substantial inter-individual variations in functional brain organization challenge accurate decoding performed at the group level. In this paper, we tested whether accurate brain decoding models can be trained entirely at the individual level. We trained several classifiers on a dense individual functional magnetic resonance imaging (fMRI) dataset for which six participants completed the entire Human Connectome Project (HCP) task battery >13 times over ten separate fMRI sessions. We evaluated nine decoding methods, from Support Vector Machines (SVM) and Multi-Layer Perceptron (MLP) to Graph Convolutional Neural Networks (GCN). All decoders were trained to classify single fMRI volumes into 21 experimental conditions simultaneously, using ∼7 h of fMRI data per participant. The best prediction accuracies were achieved with GCN and MLP models, whose performance (57-67 % accuracy) approached state-of-the-art accuracy (76 %) with models trained at the group level on >1 K hours of data from the original HCP sample. Our SVM model also performed very well (54-62 % accuracy). Feature importance maps derived from MLP -our best-performing model- revealed informative features in regions relevant to particular cognitive domains, notably in the motor cortex. We also observed that inter-subject classification achieved substantially lower accuracy than subject-specific models, indicating that our decoders learned individual-specific features. This work demonstrates that densely-sampled neuroimaging datasets can be used to train accurate brain decoding models at the individual level. We expect this work to become a useful benchmark for techniques that improve model generalization across multiple subjects and acquisition conditions.

The genitourinary impacts of electronic cigarette use: a systematic review of the literature.

PURPOSE: Electronic cigarette (e-cig) use is prevalent. The health implications of e-cig use on the genitourinary (GU) system are uncertain. This systematic review aims to evaluate how e-cig use impacts the GU system. METHODS: A systematic search was conducted in PubMed, Embase and Ovid alongside citation searching. Review articles, non-English papers, animal model/cell line studies or articles only on combustible cigarettes were excluded. Quality assessment was undertaken using the Joanna Briggs Institute checklists. The primary endpoint was the impact of e-cig use on bladder cancer incidence. Secondary outcomes included urinary carcinogens, chronic kidney disease (CKD), reproductive disorders, and other GU diseases. RESULTS: The search yielded 244 articles, 28 were ultimately included. One study assessed risk of bladder cancer and found the use of e-cig was associated with an increased odds ratio of 1.577 for its diagnosis. Twenty-one articles measured potential urinary carcinogens-including crotonaldehyde and benzene-associated with bladder cancer. Two articles evaluated the association of e-cig use with CKD and reported mixed outcomes. Three articles reported on reproductive disorders, specifically, stuttering priapism and changes to sperm quantity and quality. One study reported on other GU diseases, specifically burns to the GU system. After quality assessment, all articles were deemed to be of acceptable quality for inclusion. CONCLUSIONS: E-cig use was associated with an increased risk of bladder cancer, increased exposure to carcinogenic compounds, mixed evidence on CKD, increased risk of reproductive disorders and burns to the GU system. Further studies are needed to understand long-term GU effects.

Neural reactivation and judgements of vividness reveal separable contributions to mnemonic representation.

Mnemonic representations vary in fidelity, sharpness, and strength-qualities that can be examined using both introspective judgements of mental states and objective measures of brain activity. Subjective and objective measures are both valid ways of "reading out" the content of someone's internal mnemonic states, each with different strengths and weaknesses. St-Laurent and colleagues (2015) compared the neural correlates of memory vividness ratings with patterns of neural reactivation evoked during memory recall and found considerable overlap between the two, suggesting a common neural basis underlying these different markers of representational quality. Here we extended this work with meta-analytic methods by pooling together four neuroimaging datasets in order to contrast the neural substrates of neural reactivation and those of vividness judgements. While reactivation and vividness judgements correlated positively with one another and were associated with common univariate activity in the dorsal attention network and anterior hippocampus, some notable differences were also observed. Vividness judgments were tied to stronger activation in the striatum and dorsal attention network, together with activity suppression in default mode network nodes. We also observed a trend for reactivation to be more closely associated with early visual cortex activity. A mediation analysis found support for the hypothesis that neural reactivation is necessary for memory vividness, with activity in the anterior hippocampus associated with greater reactivation. Our results suggest that neural reactivation and vividness judgements reflect common mnemonic processes but differ in the extent to which they engage effortful, attentional processes. Additionally, the similarity between reactivation and vividness appears to arise, partly, through hippocampal engagement during memory retrieval.

Eye Movement Reinstatement and Neural Reactivation During Mental Imagery.

Half a century ago, Donald Hebb posited that mental imagery is a constructive process that emulates perception. Specifically, Hebb claimed that visual imagery results from the reactivation of neural activity associated with viewing images. He also argued that neural reactivation and imagery benefit from the re-enactment of eye movement patterns that first occurred at viewing (fixation reinstatement). To investigate these claims, we applied multivariate pattern analyses to functional MRI (fMRI) and eye tracking data collected while healthy human participants repeatedly viewed and visualized complex images. We observed that the specificity of neural reactivation correlated positively with vivid imagery and with memory for stimulus image details. Moreover, neural reactivation correlated positively with fixation reinstatement, meaning that image-specific eye movements accompanied image-specific patterns of brain activity during visualization. These findings support the conception of mental imagery as a simulation of perception, and provide evidence consistent with the supportive role of eye movement in neural reactivation.

Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans.

The dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

Recovering and preventing loss of detailed memory: differential rates of forgetting for detail types in episodic memory.

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared. Given the sensitivity of memory to loss of details, the present study sought to investigate factors that mediate the forgetting of different types of information from naturalistic episodic memories in young healthy adults. The study investigated (1) time-dependent loss of "central" and "peripheral" details from episodic memories, (2) the effectiveness of cuing with reminders to reinstate memory details, and (3) the role of retrieval in preventing forgetting. Over the course of 7 d, memory for naturalistic events (film clips) underwent a time-dependent loss of peripheral details, while memory for central details (the core or gist of events) showed significantly less loss. Giving brief reminders of the clips just before retrieval reinstated memory for peripheral details, suggesting that loss of details is not always permanent, and may reflect both a storage and retrieval deficit. Furthermore, retrieving a memory shortly after it was encoded prevented loss of both central and peripheral details, thereby promoting retention over time. We consider the implications of these results for behavioral and neurobiological models of retention and forgetting.

Functional and effective hippocampal-neocortical connectivity during construction and elaboration of autobiographical memory retrieval.

Autobiographical memory (AM) provides the opportunity to study interactions among brain areas that support the search for a specific episodic memory (construction), and the later experience of mentally reliving it (elaboration). While the hippocampus supports both construction and elaboration, it is unclear how hippocampal-neocortical connectivity differs between these stages, and how this connectivity involves the anterior and posterior segments of the hippocampus, as these have been considered to support the retrieval of general concepts and recollection processes, respectively. We acquired fMRI data in 18 healthy participants during an AM retrieval task in which participants were asked to access a specific AM (construction) and then to recollect it by recovering as many episodic details as possible (elaboration). Using multivariate analytic techniques, we examined changes in functional and effective connectivity of hippocampal-neocortical interactions during these phases of AM retrieval. We found that the left anterior hippocampus interacted with frontal areas during construction and bilateral posterior hippocampi with visual perceptual areas during elaboration, indicating key roles for both hippocampi in coordinating transient neocortical networks at both AM stages. Our findings demonstrate the importance of direct interrogation of hippocampal-neocortical interactions to better illuminate the neural dynamics underlying complex cognitive tasks such as AM retrieval.

Memory reactivation in healthy aging: evidence of stimulus-specific dedifferentiation.

We investigated how aging affects the neural specificity of mental replay, the act of conjuring up past experiences in one's mind. We used functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to quantify the similarity between brain activity elicited by the perception and memory of complex multimodal stimuli. Young and older human adults viewed and mentally replayed short videos from long-term memory while undergoing fMRI. We identified a wide array of cortical regions involved in visual, auditory, and spatial processing that supported stimulus-specific representation at perception as well as during mental replay. Evidence of age-related dedifferentiation was subtle at perception but more salient during mental replay, and age differences at perception could not account for older adults' reduced neural reactivation specificity. Performance on a post-scan recognition task for video details correlated with neural reactivation in young but not in older adults, indicating that in-scan reactivation benefited post-scan recognition in young adults, but that some older adults may have benefited from alternative rehearsal strategies. Although young adults recalled more details about the video stimuli than older adults on a post-scan recall task, patterns of neural reactivation correlated with post-scan recall in both age groups. These results demonstrate that the mechanisms supporting recall and recollection are linked to accurate neural reactivation in both young and older adults, but that age affects how efficiently these mechanisms can support memory's representational specificity in a way that cannot simply be accounted for by degraded sensory processes.

Distributed Patterns of Reactivation Predict Vividness of Recollection.

According to the principle of reactivation, memory retrieval evokes patterns of brain activity that resemble those instantiated when an event was first experienced. Intuitively, one would expect neural reactivation to contribute to recollection (i.e., the vivid impression of reliving past events), but evidence of a direct relationship between the subjective quality of recollection and multiregional reactivation of item-specific neural patterns is lacking. The current study assessed this relationship using fMRI to measure brain activity as participants viewed and mentally replayed a set of short videos. We used multivoxel pattern analysis to train a classifier to identify individual videos based on brain activity evoked during perception and tested how accurately the classifier could distinguish among videos during mental replay. Classification accuracy correlated positively with memory vividness, indicating that the specificity of multivariate brain patterns observed during memory retrieval was related to the subjective quality of a memory. In addition, we identified a set of brain regions whose univariate activity during retrieval predicted both memory vividness and the strength of the classifier's prediction irrespective of the particular video that was retrieved. Our results establish distributed patterns of neural reactivation as a valid and objective marker of the quality of recollection.

The perceptual richness of complex memory episodes is compromised by medial temporal lobe damage.

Perceptual richness, a defining feature of episodic memory, emerges from the reliving of multimodal sensory experiences. Although the importance of the medial temporal lobe (MTL) to episodic memory retrieval is well documented, the features that determine its engagement are not well characterized. The current study assessed the relationship between MTL function and episodic memory's perceptual richness. We designed a laboratory memory task meant to capture the complexity of memory for life episodes, while manipulating memory's perceptual content. Participants encoded laboratory episodes with rich (film clips) and impoverished (written narratives) perceptual content that were matched for other characteristics such as personal significance, emotionality and story content. At retrieval, participants were probed to describe the stories' perceptual features and storyline. Participants also recalled autobiographical memories (AMs) in a comparison condition. We compared the performance of patients with unilateral medial temporal lobe epilepsy (mTLE) and healthy controls to assess how damage to the MTL affects retrieval in these conditions. We observed an overall decrease in detail count in the mTLE group, along with a disproportionate deficit in perceptual details that was most acute in the AM and the perceptually enriched film clip conditions. Our results suggest that the impaired sense of reliving the past that accompanies MTL insult is mediated by a paucity of perceptual episodic memory details. We also introduce a new protocol that successfully mimics naturalistic memories while benefiting from the experimental control provided by using laboratory stimuli.

Using multivariate data reduction to predict postsurgery memory decline in patients with mesial temporal lobe epilepsy.

Predicting postsurgery memory decline is crucial to clinical decision-making for individuals with mesial temporal lobe epilepsy (mTLE) who are candidates for temporal lobe excisions. Extensive neuropsychological testing is critical to assess risk, but the numerous test scores it produces can make deriving a formal prediction of cognitive change quite complex. In order to benefit from the information contained in comprehensive memory assessment, we used principal component analysis (PCA) to simplify neuropsychological test scores (presurgical and pre- to postsurgical change) obtained from a cohort of 56 patients with mTLE into a few easily interpretable latent components. We next performed discriminant analyses using presurgery latent components to categorize seizure laterality and then regression analyses to assess how well presurgery latent components could predict postsurgery memory decline. Finally, we validated the predictive power of these regression models in an independent sample of 18 patients with mTLE. Principal component analysis identified three significant latent components that reflected IQ, verbal memory, and visuospatial memory, respectively. Together, the presurgery verbal and visuospatial memory components classified 80% of patients with mTLE correctly according to their seizure laterality. Furthermore, the presurgery verbal memory component predicted postsurgery verbal memory decline, while the presurgery visuospatial memory component predicted visuospatial memory decline. These regression models also predicted postsurgery memory decline successfully in the independent cohort of patients with mTLE. Our results demonstrate the value of data reduction techniques in identifying cognitive metrics that can characterize laterality of damage and risk of postoperative decline.

Is Engineered Tissue the Future of Bladder Reconstruction: Con.

Tissue engineering, once promising, faces significant technical challenges. Current limitations impede progression of the field, as evidenced by clinical trial failures over the past decades. Existing established surgical techniques remain the only proven, successful, and durable methods for bladder reconstruction.

Influence of aging on the neural correlates of autobiographical, episodic, and semantic memory retrieval.

We used fMRI to assess the neural correlates of autobiographical, semantic, and episodic memory retrieval in healthy young and older adults. Participants were tested with an event-related paradigm in which retrieval demand was the only factor varying between trials. A spatio-temporal partial least square analysis was conducted to identify the main patterns of activity characterizing the groups across conditions. We identified brain regions activated by all three memory conditions relative to a control condition. This pattern was expressed equally in both age groups and replicated previous findings obtained in a separate group of younger adults. We also identified regions whose activity differentiated among the different memory conditions. These patterns of differentiation were expressed less strongly in the older adults than in the young adults, a finding that was further confirmed by a barycentric discriminant analysis. This analysis showed an age-related dedifferentiation in autobiographical and episodic memory tasks but not in the semantic memory task or the control condition. These findings suggest that the activation of a common memory retrieval network is maintained with age, whereas the specific aspects of brain activity that differ with memory content are more vulnerable and less selectively engaged in older adults. Our results provide a potential neural mechanism for the well-known age differences in episodic/autobiographical memory, and preserved semantic memory, observed when older adults are compared with younger adults.

Representation of viewed and recalled film clips in patterns of brain activity in a person with developmental amnesia.

As clear memories transport us back into the past, the brain also revives prior patterns of neural activity, a phenomenon known as neural reactivation. While growing evidence indicates a link between neural reactivation and typical variations in memory performance in healthy individuals, it is unclear how and to what extent reactivation is disrupted by a memory disorder. The current study characterizes neural reactivation in a case of amnesia using Multivoxel Pattern Analysis (MVPA). We tested NC, an individual with developmental amnesia linked to a diencephalic stroke, and 19 young adult controls on a functional magnetic resonance imaging (fMRI) task during which participants viewed and recalled short videos multiple times. An encoding classifier trained and tested to identify videos based on brain activity patterns elicited at perception revealed superior classification in NC. The enhanced consistency in stimulus representation we observed in NC at encoding was accompanied by an absence of multivariate repetition suppression, which occurred over repeated viewing in the controls. Another recall classifier trained and tested to identify videos during mental replay indicated normal levels of classification in NC, despite his poor memory for stimulus content. However, a cross-condition classifier trained on perception trials and tested on mental replay trials-a strict test of reactivation-revealed significantly poorer classification in NC. Thus, while NC's brain activity was consistent and stimulus-specific during mental replay, this specificity did not reflect the reactivation of patterns elicited at perception to the same extent as controls. Fittingly, we identified brain regions for which activity supported stimulus representation during mental replay to a greater extent in NC than in controls. This activity was not modeled on perception, suggesting that compensatory patterns of representation based on generic knowledge can support consistent mental constructs when memory is faulty. Our results reveal several ways in which amnesia impacts distributed patterns of stimulus representation during encoding and retrieval.

Exploring the patterns of practice and satisfaction among female urologists in Canada.

INTRODUCTION: Our aim was to explore the satisfaction, personal and professional challenges, and practice barriers among female urologists in Canada. METHODS: A literature review was completed to design our survey. Trends with respect to career and personal satisfaction were identified, including academic advancement, mentorship, professional challenges, workplace discrimination, family satisfaction, and remuneration, among others. These key themes were formatted into 44 questions, translated into French, and distributed electronically as a survey to 80 female urology staff across Canada. RESULTS: Sixty (75.0%) women completed the survey. Many had been in practice <5 years (44.1%) and 72.9% completed a fellowship. Overall, 96.6% of women were very or somewhat satisfied with their career. Seeing more time-consuming patients and financial constraints within the healthcare system were the greatest source of dissatisfaction. Two-thirds of respondents reported that they received significant mentorship and 40% found it difficult to find a mentor during their training. Overall, 65.0% experienced gender discrimination, most commonly from a colleague or a patient. Women who practiced in the community were more likely to report experiencing discrimination compared to women practicing in an academic setting (78.1% vs. 51.9%; p=0.034). Mean time for maternity leave was 17.1 (±8.3) weeks, and 30.2% reported a pregnancy-related complication triggered by their work. Overall, 66.1% would choose urology again. CONCLUSIONS: It is important to advocate for the wellness of female urologists. To accomplish this, we need to address the challenges revealed in the survey, including supporting women on maternity leave, improving mentorship, and prioritizing female urology leadership initiatives. We have established a formal circle of support within the urology community in Canada to achieve these goals.

Does the cingulate cortex contribute to spatial conditional associative learning in the rat?

Rats with lesions to the anterior or posterior (retrosplenial) region of the cingulate cortex and rats with lesions that included both the anterior and posterior cingulate cortex were tested on a visual-spatial conditional task in which they had to learn to approach one of the two objects depending on the spatial context within which they were embedded. Lesions restricted to either the anterior or the retrosplenial cingulate region did not impair learning of this task which is known to be very sensitive to the effects of hippocampal lesions. Complete lesions of the cingulate cortex gave rise to only a minor retardation in learning. In contrast, lesions to the retrosplenial cortex impaired performance on a spatial navigation task and the classic radial maze. These results suggest that the retrosplenial portion of the cingulate region forms part of a hippocampal circuit underlying learning about spatial responses. The dissociation between the effects of lesions of the cingulate region on different classes of behavior known to be associated with hippocampal function suggests that, although this neural structure does play a role in an extended hippocampal circuit underlying spatial learning, its role in such learning may be a selective one.

How Multiple Retrievals Affect Neural Reactivation in Young and Older Adults.

OBJECTIVES: Aging can reduce the specificity with which memory episodes are represented as distributed patterns of brain activity. It remains unclear, however, whether repeated encoding and retrieval of stimuli modulate this decline. Memory repetition is thought to promote semanticization, a transformative process during which episodic memory becomes gradually decontextualized and abstracted. Because semantic memory is considered more resilient to aging than context-rich episodic memory, we hypothesized that repeated retrieval would affect cortical reinstatement differently in young versus older adults. METHODS: We reanalyzed data from young and older adults undergoing functional magnetic resonance imaging while repeatedly viewing and recalling short videos. We derived trial-unique multivariate measures of similarity between video-specific brain activity patterns elicited at perception and at recall, which we compared between age groups at each repetition. RESULTS: With repetition, memory representation became gradually more distinct from perception in young adults, as reinstatement specificity converged downward toward levels observed in the older group. In older adults, alternative representations that were item-specific but orthogonal to patterns elicited at perception became more salient with repetition. DISCUSSION: Repetition transformed dominant patterns of memory representation away and orthogonally from perception in young and older adults, respectively. Although distinct, both changes are consistent with repetition-induced semanticization.