Statistical learning guides visual attention within iconic memory.

The present study investigated interactions between iconic memory and long-term memory during visual search. The contextual cueing paradigm was combined with a brief presentation procedure to determine whether statistical learning takes place from flashed displays and acts as a cue to guide spatial attention within iconic memory in subsequent visual search. In five experiments, participants were exposed to search displays that were presented for only 50 ms and had to detect a target among 11 distractors. Half of those displays were repeated across the task and half were presented once. The results revealed a contextual cueing effect in four of the experiments, revealing the capacity of the human brain to extract spatial regularities from very brief visual presentations and to later activate this knowledge to guide attention within a representation briefly maintained within iconic memory.

The fate of visual long term memories for images across weeks in adults and children.

What is the content and the format of visual memories in Long Term Memory (LTM)? Is it similar in adults and children? To address these issues, we investigated, in both adults and 9-year-old children, how visual LTM is affected over time and whether visual vs semantic features are affected differentially. In a learning phase, participants were exposed to hundreds of meaningless and meaningful images presented once or twice for either 120 ms or 1920 ms. Memory was assessed using a recognition task either immediately after learning or after a delay of three or six weeks. The results suggest that multiple and extended exposures are crucial for retaining an image for several weeks. Although a benefit was observed in the meaningful condition when memory was assessed immediately after learning, this benefit tended to disappear over weeks, especially when the images were presented twice for 1920 ms. This pattern was observed for both adults and children. Together, the results call into question the dominant models of LTM for images: although semantic information enhances the encoding & maintaining of images in LTM when assessed immediately, this seems not critical for LTM over weeks.

Operative and Midterm Oncological Outcome of Focal Salvage Cryotherapy for Localized Prostate Cancer.

BACKGROUND: Local recurrence after radiation therapy for prostate cancer is a major clinical issue. Various local treatments are available with mitigated functional and oncological outcomes. The aim of the present study was to evaluate perioperative and oncological results of salvage cryotherapy (CT) as treatment of local recurrence of prostate cancer. METHODS: We retrospectively reviewed all patients treated with hemi-prostatic salvage CT for local recurrence of prostate cancer in 1 academic hospital between November 2011 and April 2019. Local recurrence was defined according to the Phoenix criteria (prostate-specific antigen [PSA] nadir + 2 ng/mL), associated with a prostatic MRI target lesion and confirmed by biopsy. Perioperative and functional complications were collected. Cox regression was conducted to assess factors associated with time to initiation of androgen deprivation therapy (ADT). Statistical analyses were conducted using R Studio. RESULTS: A total of 29 patients were treated with an average follow-up of 37.6 months. Median age at CT was 77 years. Median PSA before CT was 5.1 ng/mL (min-max: 2.74-18). 17.2% of patients displayed a high D'Amico risk group. Median hospital stay was 1.4 days. Four patients (13.8%) experienced postoperative acute urinary retention. Nineteen patients (65.5%) experienced late functional complications (3 erectile dysfunctions, 3 stress incontinence, and 13 urinary frequency). Fourteen patients displayed recurrence after salvage treatment (48.2%). Median time to introduction of ADT was 15.1 months. ADT-free survival at 1 and 2 years was, respectively, 74% and 61%. In multivariate analysis, ISUP score 4 and PSA nadir <1 ng/mL after CT were significantly associated with time to ADT initiation. CONCLUSIONS: Salvage focal CT may delay the use of ADT in locally recurrent prostate cancer after RT and offers an alternative for eligible patients. The technique was feasible with acceptable perioperative morbidity and acceptable midterm oncological outcome.

Perioperative outcomes of transurethral resection for t1 bladder tumors: quality evaluation based on patient, tumor and surgeon criteria.

INTRODUCTION: Transurethral resection of bladder tumor (TURBT) is a fundamental but challenging step in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). The first- and second-look TURBT are central in the management of T1 tumors. MATERIALS AND METHODS: We retrospectively reviewed all patients treated with TURBT for T1 urothelial cell carcinoma (UCC) of the bladder in one academic institution between 2007 and 2017. Quality of TURBT was evaluated based on the presence/absence of muscle on pathology report, the presence/absence of residual tumor on the second look and the occurrence of complications. Patient-, surgeon- and tumor-related factors were investigated for their association with TURBT quality. RESULTS: 283 patients were included. Second-look resection was performed after a mean delay of 54 days. Muscle was observed in 85.9% of the samples on the first TURBT. On the second-look resection, UCC was observed in 52.3% of the samples. 38 complications were reported after the first TURBT (13.4%). Surgeon's experience was the only factor significantly associated with occurrence of post-operative complications (OR = 0.40; p = 0.04). Location of the tumor at the bottom of the bladder was a risk factor for not finding muscle at pathological analysis (OR = 0.20; p = 0.06). Male gender, multiplicity and tumor located at the bottom of the bladder were significantly associated with residual disease on reTURBT. In multivariate analysis, only male gender (OR = 4.71; p = 0.02) and tumor multiplicity remained significant (OR for unique tumor = 0.36; p = 0.02). CONCLUSION: TURBT is a challenging procedure and surgeon's experience is crucial in reducing the rate of post-operative complications. Technical difficulties resulting from patient's gender, tumor location or number of tumors may be as important as oncological factors in deciding whether or not to perform a second-look resection.

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study.

OBJECTIVES: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB. METHODS: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression. RESULTS: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602). CONCLUSIONS: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.

[Conservative management of genital prolapse]. / Traitement non chirurgical des prolapsus génitaux.

Conservative management of genital prolapse may be an alternative to surgical treatment, if prolapse is moderate or has few symptoms, and for frail patients when surgery is contraindicated. Non-surgical management consists of several measures. Topical hormonal treatments improve patients' comfort, but their efficiency was not proven. Pessaries achieve anatomical reintegration of prolapse and reach up to 80% satisfaction rate. Cube-shaped pessaries have to be changed daily, permanent ring pessaries require to be changed by a doctor every 3 months. Pelvic floor muscle training can improve symptoms in moderate forms and delays the prolapse worsening. Prevention is important, associating measures such as fighting obesity, constipation, coughing, eviction of heavy loads carrying and avoiding pelvic floor high solicitating sports.

TRAITEMENT NON CHIRURGICAL DES PROLAPSUS GÉNITAUX Le traitement conservateur des prolapsus des organes pelviens peut être une alternative au traitement chirurgical lorsque le prolapsus est modéré ou peu symptomatique, et chez des patientes fragiles, lorsque la chirurgie est contre-indiquée. Plusieurs mesures s'intègrent dans une prise en charge non chirurgicale. Les traitements hormonaux améliorent le confort des patientes sans que leur efficacité puisse être démontrée. Les pessaires permettent la réduction anatomique du prolapsus. En forme de cube pour un changement quotidien ou d'anneau conservé à demeure avec changement par un médecin tous les 3 mois, ils permettent d'obtenir jusqu'à 80 % de satisfaction des patientes, et sont le plus souvent associés aux estrogènes. La rééducation périnéale améliorerait les symptômes dans les formes modérées, et retarderait l'aggravation du prolapsus. Les mesures préventives sont importantes, et réunissent la lutte contre l'obésité, la constipation, la toux, et l'éviction du port de charges lourdes et de certains sports.

CD8+PD-1-ILT2+ T Cells Are an Intratumoral Cytotoxic Population Selectively Inhibited by the Immune-Checkpoint HLA-G.

Only some cancer patients respond to the immune-checkpoint inhibitors being used in the clinic, and other therapeutic targets are sought. Here, we investigated the HLA-G/ILT2 checkpoint in clear-cell renal-cell carcinoma (ccRCC) patients and focused on tumor-infiltrating CD8+ T lymphocytes (TIL) expressing the HLA-G receptor ILT2. Using transcriptomics and flow cytometry, we characterized both peripheral blood and tumor-infiltrating CD8+ILT2+ T cells from cancer patients as late-differentiated CD27-CD28-CD57+ cytotoxic effectors. We observed a clear dichotomy between CD8+ILT2+ and CD8+PD-1+ TIL subsets. These subsets, which were sometimes present at comparable frequencies in TIL populations, barely overlapped phenotypically and were distinguished by expression of exclusive sets of surface molecules that included checkpoint molecules and activating and inhibitory receptors. CD8+ILT2+ TILs displayed a more mature phenotype and higher expression of cytotoxic molecules. In ex vivo functional experiments with both peripheral blood T cells and TILs, CD8+ILT2+ T cells displayed significantly higher cytotoxicity and IFNγ production than their ILT2- (peripheral blood mononuclear cells, PBMC) and PD-1+ (TILs) counterparts. HLA-G expression by target cells specifically inhibited CD8+ILT2+ T-cell cytotoxicity, but not that of their CD8+ILT2- (PBMC) or CD8+PD-1+ (TIL) counterparts, an effect counteracted by blocking the HLA-G/ILT2 interaction. CD8+ILT2+ TILs may therefore constitute an untapped reservoir of fully differentiated cytotoxic T cells within the tumor microenvironment, independent of the PD1+ TILs targeted by immune therapies, and specifically inhibited by HLA-G. These results emphasize the potential of therapeutically targeting the HLA-G/ILT2 checkpoint in HLA-G+ tumors, either concomitantly with anti-PD-1/PD-L1 or in cases of nonresponsiveness to anti-PD-1/PD-L1.

Prediction of non-muscle-invasive bladder cancer recurrence by measurement of checkpoint HLAG's receptor ILT2 on peripheral CD8+ T cells.

BACKGROUND AND OBJECTIVE: Recurrence of non-muscle invasive bladder cancer (NMIBC) after initial management occurs in 60-70% of patients. Predictive criteria for recurrence remain only clinical and pathological. The aim of this study was to investigate the prognostic significance of the proportion of checkpoint HLA-G's receptor ILT2-expressing peripheral CD8+ T cells. RESULTS: The proportion of CD4+ILT2+and CD8+ILT2+ T cells was not increased in NMIBC compared to controls. However, a strong association was found between recurrence and CD8+ILT2+ T cell population levels (p = 0.0006). Two-year recurrence-free survival was 83% in patients with less than 18% CD8+ILT2+ T cells, 39% in the intermediary group, and 12% in patients with more than 46% CD8+ILT2+ T cells. Multivariate analyses demonstrated that the proportion of CD8+ILT2+ T cells was an independent predictive factor for recurrence. Adding CD8+ILT2+ T cells population level to clinical variables increased the predictive accuracy of the model by 4.5%. MATERIALS AND METHODS: All patients treated for NMIBC between 2012 and 2014 were included prospectively. Blood samples, tumor and clinico-pathological characteristics were collected. HLA-G expression was measured using IHC, and CD8+ILT2+ T cell levels using flow cytometry. Association between HLA-G and CD8+ILT2+ T cell population levels with NMIBC risk of recurrence was investigated using Cox regression analyses. Prediction was measured using the concordance index statistic. CONCLUSIONS: We demonstrated a strong association between the proportion of circulating CD8+ILT2+ T cells and NMIBC risk of recurrence. Gain in prediction was substantial. If externally validated, such immunological marker could be integrated to predict NMIBC recurrence.

On the limits of statistical learning: Intertrial contextual cueing is confined to temporally close contingencies.

Since the seminal study by Chun and Jiang (Cognitive Psychology, 36, 28-71, 1998), a large body of research based on the contextual-cueing paradigm has shown that the cognitive system is capable of extracting statistical contingencies from visual environments. Most of these studies have focused on how individuals learn regularities found within an intratrial temporal window: A context predicts the target position within a given trial. However, Ono, Jiang, and Kawahara (Journal of Experimental Psychology, 31, 703-712, 2005) provided evidence of an intertrial implicit-learning effect when a distractor configuration in preceding trials N - 1 predicted the target location in trials N. The aim of the present study was to gain further insight into this effect by examining whether it occurs when predictive relationships are impeded by interfering task-relevant noise (Experiments 2 and 3) or by a long delay (Experiments 1, 4, and 5). Our results replicated the intertrial contextual-cueing effect, which occurred in the condition of temporally close contingencies. However, there was no evidence of integration across long-range spatiotemporal contingencies, suggesting a temporal limitation of statistical learning.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

BACKGROUND: Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series. METHODS: Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 48 months (95% CI = [45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4 years, HR = 1.97, 95% CI = [1.71; 2.27], p < 0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p < 0.0001). In multivariate analysis, primary Gleason score of 4 (HR = 1.81, 95% CI = [1.55; 2.12], p < 0.0001) and PPBC ≥ 50% (HR = 1.26, 95% CI = [1.02; 1.56], p = 0.0286) were significant preoperative predictors for worse PSA-RFS. CONCLUSIONS: This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

Investigating implicit statistical learning mechanisms through contextual cueing.

Since its inception, the contextual cueing (CC) paradigm has generated considerable interest in various fields of cognitive sciences because it constitutes an elegant approach to understanding how statistical learning (SL) mechanisms can detect contextual regularities during a visual search. In this article we review and discuss five aspects of CC: (i) the implicit nature of learning, (ii) the mechanisms involved in CC, (iii) the mediating factors affecting CC, (iv) the generalization of CC phenomena, and (v) the dissociation between implicit and explicit CC phenomena. The findings suggest that implicit SL is an inherent component of ongoing processing which operates through clustering, associative, and reinforcement processes at various levels of sensory-motor processing, and might result from simple spike-timing-dependent plasticity.

Baboons' response speed is biased by their moods.

The affect-as-information hypothesis (e.g., Schwarz & Clore, 2003), predicts that the positive or negative valence of our mood differentially affects our processing of the details of the environment. However, this hypothesis has only been tested with mood induction procedures and fairly complex cognitive tasks in humans. Here, six baboons (Papio papio) living in a social group had free access to a computerized visual search task on which they were over-trained. Trials that immediately followed a spontaneously expressed emotional behavior were analyzed, ruling out possible biases due to induction procedures. RTs following negatively valenced behaviors are slower than those following neutral and positively valenced behaviors, respectively. Thus, moods affect the performance of nonhuman primates tested in highly automatized tasks, as it does in humans during tasks with much higher cognitive demands. These findings reveal a presumably universal and adaptive mechanism by which moods influence performance in various ecological contexts.

The emergence of explicit knowledge from implicit learning.

Substantial evidence has highlighted the ability of observers to incidentally extract statistical contingencies present in visual environments. This study examined whether the knowledge extracted regarding statistical contingencies is unconscious initially, even when it becomes fully accessible to conscious awareness after extensive training. Using a "typical" contextual cuing procedure adapted to real-world scenes, we first observed that, after extensive training in searching for a target within repeated scenes, knowledge about regularities was associated with conscious awareness (Experiment 1). However, both subjective and objective measures of consciousness revealed that in the early phase of training, learning of regular structures first takes place at an unconscious level (Experiments 2 and 3). These results are discussed in the light of the causal relationships between learning and consciousness.

Learning of spatial statistics in nonhuman primates: contextual cueing in baboons (Papio papio).

A growing number of theories of cognition suggest that many of our behaviors result from the ability to implicitly extract and use statistical redundancies present in complex environments. In an attempt to develop an animal model of statistical learning mechanisms in humans, the current study investigated spatial contextual cueing (CC) in nonhuman primates. Twenty-five baboons (Papio papio) were trained to search for a target (T) embedded within configurations of distrators (L) that were either predictive or non-predictive of the target location. Baboons exhibited an early CC effect, which remained intact after a 6-week delay and stable across extensive training of 20,000 trials. These results demonstrate the baboons' ability to learn spatial contingencies, as well as the robustness of CC as a cognitive phenomenon across species. Nevertheless, in both the youngest and oldest baboons, CC required many more trials to emerge than in baboons of intermediate age. As a whole, these results reveal strong similarities between CC in humans and baboons, suggesting similar statistical learning mechanisms in these two species. Therefore, baboons provide a valid model to investigate how statistical learning mechanisms develop and/or age during the life span, as well as how these mechanisms are implemented in neural networks, and how they have evolved throughout the phylogeny.

How visual and semantic information influence learning in familiar contexts.

Previous research using the contextual cuing paradigm has revealed both quantitative and qualitative differences in learning depending on whether repeated contexts are defined by letter arrays or real-world scenes. To clarify the relative contributions of visual features and semantic information likely to account for such differences, the typical contextual cuing procedure was adapted to use meaningless but nevertheless visually complex images. The data in reaction time and in eye movements show that, like scenes, such repeated contexts can trigger large, stable, and explicit cuing effects, and that those effects result from facilitated attentional guidance. Like simpler stimulus arrays, however, those effects were impaired by a sudden change of a repeating image's color scheme at the end of the learning phase (Experiment 1), or when the repeated images were presented in a different and unique color scheme across each presentation (Experiment 2). In both cases, search was driven by explicit memory. Collectively, these results suggest that semantic information is not required for conscious awareness of context-target covariation, but it plays a primary role in overcoming variability in specific features within familiar displays.

A bias to detail: how hand position modulates visual learning and visual memory.

In this report, we examine whether and how altered aspects of perception and attention near the hands affect one's learning of to-be-remembered visual material. We employed the contextual cuing paradigm of visual learning in two experiments. Participants searched for a target embedded within images of fractals and other complex geometrical patterns while either holding their hands near to or far from the stimuli. When visual features and structural patterns remained constant across to-be-learned images (Exp. 1), no difference emerged between hand postures in the observed rates of learning. However, when to-be-learned scenes maintained structural pattern information but changed in color (Exp. 2), participants exhibited substantially slower rates of learning when holding their hands near the material. This finding shows that learning near the hands is impaired in situations in which common information must be abstracted from visually unique images, suggesting a bias toward detail-oriented processing near the hands.

Categorical implicit learning in real-world scenes: evidence from contextual cueing.

The present study examined the extent to which learning mechanisms are deployed on semantic-categorical regularities during a visual searching within real-world scenes. The contextual cueing paradigm was used with photographs of indoor scenes in which the semantic category did or did not predict the target position on the screen. No evidence of a facilitation effect was observed in the predictive condition compared to the nonpredictive condition when participants were merely instructed to search for a target T or L (Experiment 1). However, a rapid contextual cueing effect occurred when each display containing the search target was preceded by a preview of the scene on which participants had to make a decision regarding the scene's category (Experiment 2). A follow-up explicit memory task indicated that this benefit resulted from implicit learning. Similar implicit contextual cueing effects were also obtained when the scene to categorize was different from the subsequent search scene (Experiment 3) and when a mere preview of the search scene preceded the visual searching (Experiment 4). These results suggested that if enhancing the processing of the scene was required with the present material, such implicit semantic learning can nevertheless take place when the category is task irrelevant.

Semantic contextual cuing and visual attention.

Since M. M. Chun and Y. Jiang's (1998) original study, a large body of research based on the contextual cuing paradigm has shown that the visuocognitive system is capable of capturing certain regularities in the environment in an implicit way. The present study investigated whether regularities based on the semantic category membership of the context can be learned implicitly and whether that learning depends on attention. The contextual cuing paradigm was used with lexical displays in which the semantic category of the contextual words either did or did not predict the target location. Experiments 1 and 2 revealed that implicit contextual cuing effects can be extended to semantic category regularities. Experiments 3 and 4 indicated an implicit contextual cuing effect when the predictive context appeared in an attended color but not when the predictive context appeared in an ignored color. However, when the previously ignored context suddenly became attended, it immediately facilitated performance. In contrast, when the previously attended context suddenly became ignored, no benefit was observed. Results suggest that the expression of implicit semantic knowledge depends on attention but that latent learning can nevertheless take place outside the attentional field.