Search

The incidence of early onset colorectal cancer (EOCRC) in Canada has increased. To address the growing incidence of EOCRC, Colorectal Cancer Canada (CCC) developed the Never Too Young (N2Y) program to identify gaps in care and evaluate patient and caregiver experiences with CRC. The survey was available online using SurveyMonkey across Canada between 12 December 2022 and 1 May 2023. The patient and caregiver survey consisted of 113 and 94 questions, respectively. A total of 108 EOCRC patients and 20 caregivers completed the survey. Many respondents were unaware of EOCRC (41.6%) and the disease symptoms (45.2%) before diagnosis. Patient age at diagnosis was between 45 and 50 years in 31.7%, and 72.8% of them were diagnosed at stage III or IV. A perception of an initial misdiagnosis was common (67.4%) for EOCRC patients, and 51.2% felt dismissed due to their age. Patients and caregivers reported impacts of EOCRC on their mental health, with 70.9% of patients expressing a need for support with depression and 93.3% of caregivers experiencing a constant fear of recurrence of their loved one's cancer. Improving the Canadian population's awareness of EOCRC (e.g., CRC symptoms) is important for ensuring timely diagnoses. Similarly, it is critical to ensure that healthcare providers are aware of the increase in EOCRC cases and the unique needs of these patients. Re-evaluation of the CRC screening age should be undertaken in Canada to determine whether lowering the start age to 45 years will improve outcomes in this demographic. [ABSTRACT FROM AUTHOR]

Despite ongoing screening efforts, colorectal cancer (CRC) remains a leading cause of death in Canada. The aim of this study was to better understand the experiences of Canadian CRC patients with their family practitioners (FPs) during and after their CRC diagnosis. Patient-reported data were collected through an online questionnaire to understand their CRC diagnosis experiences and identify potential gaps in care. Various factors contributing to challenges throughout a patient's CRC diagnosis (e.g., delayed CRC diagnosis) were determined using descriptive, qualitative, and inferential analyses. These factors could be targeted to optimize CRC care. This study found that 40.6% of the 175 respondents were unaware of at least one of the following aspects of CRC prior to their diagnosis: early-age onset (EAO), symptoms, and screening procedures. While 84.6% had access to a family physician (FP) before their diagnosis, only 17.7% were diagnosed by FPs. Higher proportions of younger individuals experienced misdiagnoses and felt dismissed compared to older individuals. Only half felt fully informed about their diagnosis when it was explained to them by their FP, while 53.1% had their diagnosis explained in plain language. Transitioning towards patient-centred care would promote pre-diagnosis CRC awareness, address differences in management of CRC care (e.g., dismissal and support), and accommodate for age and health-literacy-related disparities, thereby improving CRC care pathways for patients. Future research should investigate FPs experiences in detecting CRC cases to develop educational resources and recommendations, enhancing early detection and improving patient outcomes (1). [ABSTRACT FROM AUTHOR]

Canada has one of the most complex and rigorous drug approval and public reimbursement processes and is, unfortunately, one of the countries with the longest delays in drug access. To assess the overall impact of systemic delays in access to cancer therapy, a targeted literature review (TLR) was performed to identify studies associated with the clinical, economic, and quality of life impacts of delayed access to oncology drugs. Using MEDLINE/PubMed databases and snowballing, four unique records met the eligibility criteria. Results revealed that clinical outcomes were the most impacted by systemic delays in access to oncology drugs (e.g., life years lost, overall survival, and progression-free survival). The four articles retrieved by the TLR specifically illustrated that a substantial number of life years could potentially be saved by increasing systemic efficiency regarding the development, approval, and reimbursement processes of new drugs for advanced malignancies. It is imperative that initiatives are put in place to improve the performance and speed of Canadian drug regulatory and health technology assessment (HTA) processes, especially for new cancer therapeutics. The proposed solutions in this paper include better coordination between HTA and Canadian payers to harmonize coverage decisions, international collaborations, information sharing, and national standards for timeliness in oncology drug access. [ABSTRACT FROM AUTHOR]

Background: Low patient activation (PA) is associated with worse postoperative outcomes, however, its impact on the effectiveness of digital health interventions is unknown. We sought to determine the impact of PA on the effectiveness of digital health application for remote post-discharge follow-up for patients undergoing elective colectomy. Methods: Data analysis included a control cohort (CC) of patients undergoing elective colorectal surgery from 10/2017 to 04/2018 without the digital health intervention and a digital application cohort (DAC) that received a smart phone application for remote post-discharge follow-up from 03/2021 to 08/2022, including a subset of same-day discharge (SDD) patients. PA was measured using the Patient Activation Measure (PAM; score 0–100) and categorized into low (< 55.1) and high (≥ 55.1). The PAM was administered 4–6 weeks before surgery in the DAC group and on postoperative day (POD) 1 in the CC group. The main outcome measure was 30-day emergency department (ED) visits. Results: A total of 164 patients were included (89DAC with 50 SDD, 75CC), with no differences in patient characteristics other than more stoma closures in the DAC group. Overall, 77% of patients had high PA level, with no difference between CC and DAC (77% vs. 81%, p = 0.25). There was no difference in ED visits between CC and DAC (19% vs. 18%, p = 0.90). Overall, low PA was associated more ED visits (29% vs 14%, p = 0.04). In the SDD subgroup, low PA patients had more ED visits (38% vs. 7%, p = 0.015). PA level did not affect app usage metrics. On multiple regression, only low PA remained independently associated with ED visits (OR 3.42, 95%CI 1.27, 9.24). Conclusion: Low PA remains an important predictor of surgical outcomes after elective colorectal surgery regardless of the use of a digital health application for remote post-discharge follow-up. This suggests that improving PA levels may improve postoperative outcomes. [ABSTRACT FROM AUTHOR]

Sleep difficulties are a common symptom in cancer patients at different stages of treatment trajectory and may lead to numerous negative consequences for which management is required. This pilot Randomized Controlled Trial (RCT) aims to assess the potential effectiveness of home-based prehabilitation intervention (prehab) on sleep quality and parameters compared to standard care (SOC) in colorectal cancer patients during the preoperative period and up to 8 weeks after the surgery. One hundred two participants (48.3% female, mean age 65 years) scheduled for elective resection of colorectal cancer were randomized to the prehab (n = 50) or the SOC (n = 52) groups. Recruitment and retention rates were 54% and 72%, respectively. Measures were completed at the baseline and preoperative, 4- and 8-week after-surgery follow-ups. Our mixed models' analyses revealed no significant differences between groups observed over time for all subjective and objective sleep parameters. A small positive change was observed in the perceived sleep quality only at the preoperative time point for the prehabilitation group compared to the SOC group, with an effect size d = 0.11 and a confidence interval (CI) between − 2.1 and − 0.1, p =.048. Prehab group patients with high anxiety showed a significant improvement in the rate of change of sleep duration over time compared to the SOC group, with a difference of 110 min between baseline and 8 weeks after surgery (d = 0.51, 95% CI: 92.3 to 127.7, p =.02). Multimodal prehabilitation intervention is feasible in colorectal cancer patients and may improve sleep duration for patients with high anxiety symptoms. Future large-scale RCTs are needed to confirm our results. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused disruptions in colorectal cancer (CRC) care by interrupting CRC screening across Canada, posing problems for program participants, patients, and physicians and no clear understanding of how provincial healthcare systems would adapt in the face of another pandemic or shock to the system. A nationwide online survey targeted to members of the National Colorectal Cancer Screening Network (NCCSN) using the SurveyMonkey platform was conducted to gain insight into the impact of the pandemic on CRC screening from March 2020 to March 2022 across all thirteen Canadian jurisdictions. The survey included 25 multiple-choice and free-text questions. Both quantitative and qualitative methods were used to analyze the data using Microsoft Excel and NVivo software. Twenty-one provincial and territorial representatives participated in the survey conducted between 13 May 2022 and 27 October 2022. All jurisdictions (100%) reported decreased screenings, including fecal immunochemical testing (FIT) or Fecal Occult Blood testing (FOBT) procedures, and subsequent diagnostic colonoscopies. The average wait time for colonoscopies due to a positive FIT/FOBT was 76 days. To mitigate the backlog and initiate an effective intervention plan, representatives highlighted some key points, including the importance of prioritizing high-risk patients. Survey results concluded that the COVID-19 pandemic impacted CRC screening across Canada. This landscape assessment can help inform intervention measures and policy-related solutions to create greater resilience for CRC screening in provincial and territorial healthcare systems. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence to support discharge prior to gastrointestinal recovery following colorectal surgery. Furthermore, many patients are discharged early despite being excluded from an ambulatory colectomy pathway. The objective of this study was to determine the outcomes of patients discharged early following laparoscopic colectomy in an enhanced recovery pathway (ERP). Methods: A retrospective review of all adult patients undergoing elective laparoscopic colectomy at a single university-affiliated colorectal referral center (08/2017–06/2021) was performed. Patients were included if they had undergone elective laparoscopic colectomy or ileostomy closure and excluded if they had been enrolled in an ambulatory colectomy pathway. Patients were then divided into three groups: LOS =1 day, LOS 2–3 days, and LOS 4+ days. The main outcomes were 30-day emergency room (ER) visits and readmissions. Reasons for inpatient stay per post-operative day (POD) were also recorded. Results: A total of 497 patients were included [LOS1 n = 63 (13%), LOS2–3 n = 284 (57%), and LOS4+ n = 150 (30%)]. There were no differences in patient characteristics, diagnosis, or procedure between the groups. Patients were discharged with gastrointestinal recovery (GI-3) in 54% LOS1 vs. 98% LOS2–3 vs. 100% LOS4+ (p<0.001). Shorter procedure duration, transversus abdominus plane block, and lower opioid requirements were associated with shorter LOS (p<0.001). The absence of flatus was the most common reason to keep patients hospitalized: 61% on POD1, 21% on POD2, and 8% on POD3 (p<0.001). There were no differences in 30-day emergency visits, or readmission between the groups. In the LOS1 group, there were no differences in outcomes between patients with full return of bowel function at discharge compared to those without. Conclusion: Discharge on POD1 was not associated with increased emergency department use, complications, or readmissions. Importantly, full return of bowel function at discharge did not affect outcomes. There may be potential to expand eligibility criteria for ambulatory colectomy protocol. [ABSTRACT FROM AUTHOR]

The multisensory (deep) layers of the superior colliculus (SC) play an important role in detecting, localizing, and guiding orientation responses to salient events in the environment. Essential to this role is the ability of SC neurons to enhance their responses to events detected by more than one sensory modality and to become desensitized ('attenuated' or 'habituated') or sensitized ('potentiated') to events that are predictable via modulatory dynamics. To identify the nature of these modulatory dynamics, we examined how the repetition of different sensory stimuli affected the unisensory and multisensory responses of neurons in the cat SC. Neurons were presented with 2HZ stimulus trains of three identical visual, auditory, or combined visual–auditory stimuli, followed by a fourth stimulus that was either the same or different ('switch'). Modulatory dynamics proved to be sensory-specific: they did not transfer when the stimulus switched to another modality. However, they did transfer when switching from the visual–auditory stimulus train to either of its modality-specific component stimuli and vice versa. These observations suggest that predictions, in the form of modulatory dynamics induced by stimulus repetition, are independently sourced from and applied to the modality-specific inputs to the multisensory neuron. This falsifies several plausible mechanisms for these modulatory dynamics: they neither produce general changes in the neuron's transform, nor are they dependent on the neuron's output. [ABSTRACT FROM AUTHOR]

Hemianopia (unilateral blindness), a common consequence of stroke and trauma to visual cortex, is a debilitating disorder for which there are few treatments. Research in an animal model has suggested that visual-auditory stimulation therapy, which exploits the multisensory architecture of the brain, may be effective in restoring visual sensitivity in hemianopia. It was tested in two male human patients who were hemianopic for at least 8 months following a stroke. The patients were repeatedly exposed to congruent visual-auditory stimuli within their blinded hemifield during 2 h sessions over several weeks. The results were dramatic. Both recovered the ability to detect and describe visual stimuli throughout their formerly blind field within a few weeks. They could also localize these stimuli, identify some of their features, and perceive multiple visual stimuli simultaneously in both fields. These results indicate that the multisensory therapy is a rapid and effective method for restoring visual function in hemianopia. [ABSTRACT FROM AUTHOR]

Introduction: A high proportion of colorectal surgery patients within an enhanced recovery pathway (ERP) do not experience complications but remain hospitalized mainly waiting for gastrointestinal (GI) recovery. Accurate identification of these patients may allow discharge prior to the return of GI function. Therefore, the objective of this study is to determine if tolerating clear fluid (CF) on postoperative day (POD) 0 was associated with uncomplicated return of GI function after laparoscopic colorectal surgery. Methods: Pooled data from three prospective studies from a single specialist colorectal referral center were analyzed (2013–2019). The present study included adult patients that underwent elective laparoscopic colectomy without stoma. Postoperative GI symptoms were collected daily in all three datasets. The main exposure variable, whether CF diet was tolerated on POD0, was defined as patients drinking at least 300 mL of CF without any nausea, anti-emetics, or vomiting (CF+ vs CF−). The main outcome measure was time to GI-3 (tolerating solid diet and passage of gas or stools). Results: A total of 221 patients were included in this study, including 69% CF+ and 31% CF−. The groups were similar in age, gender, and comorbidities, but the CF− patients were more likely to have surgery for inflammatory bowel disease. CF+ patients had faster time to GI-3 (mean 1.6d (SD 0.7) vs. 2.3d (SD 1.5), p < 0.001). The CF+ group also experienced fewer complications (19% vs. 35%, p = 0.009), shorter mean LOS (mean 3.6d (SD 2.9) vs. 6.2d (SD 9.4), p = 0.002), and were more likely to be discharged by the target LOS (66% vs. 50%, p = 0.024). Conclusion: Toleration of CF on POD0 was associated with faster return of GI function, fewer complications, and shorter LOS. This may be used as a criteria for potential discharge prior to full return of GI function after laparoscopic colectomy within an ERP. [ABSTRACT FROM AUTHOR]

Bacillus mycoides Ko01 strain grows rapidly and forms extensive rhizoidal colonies on hard agar despite limited surface water availability. The agar concentrations affect the handedness of the colonies as well as other colony architectures. In this study, we found that the local curvature of cell chains in the developing colonies did not vary based on the agar concentration, while concentration does affect the handedness of chirality at the macroscale. This result suggests independence between the microscale filament curvature and macroscale colony chirality. In addition, we discovered a novel microscopic property of cells that has not been observed before: T-shaped budding under extremely low surface water availability conditions. We propose that this feature gives rise to chaotic colony morphology. Together with bundling of chains, cells form a unique set of spatial arrangements under different surface water availability. These properties appear to impact the structural features of thick tendrils, and thereby the overall morphology of colonies. Our study provides additional insights as to how bacteria proliferate, spread, and develop macroscale colony architecture under water-limited conditions. [ABSTRACT FROM AUTHOR]

The superior colliculus (SC) is richly endowed with neurons that integrate cues from different senses to enhance their physiological responses and the overt behaviors they mediate. However, in the absence of experience with cross‐modal combinations (e.g., visual–auditory), they fail to develop this characteristic multisensory capability: Their multisensory responses are no greater than their most effective unisensory responses. Presumably, this impairment in neural development would be reflected as corresponding impairments in SC‐mediated behavioral capabilities such as detection and localization performance. Here, we tested that assumption directly in cats raised to adulthood in darkness. They, along with a normally reared cohort, were trained to approach brief visual or auditory stimuli. The animals were then tested with these stimuli individually and in combination under ambient light conditions consistent with their rearing conditions and home environment as well as under the opposite lighting condition. As expected, normally reared animals detected and localized the cross‐modal combinations significantly better than their individual component stimuli. However, dark‐reared animals showed significant defects in multisensory detection and localization performance. The results indicate that a physiological impairment in single multisensory SC neurons is predictive of an impairment in overt multisensory behaviors. [ABSTRACT FROM AUTHOR]

The brain enhances its perceptual and behavioral decisions by integrating information from its multiple senses in what are believed to be optimal ways. This phenomenon of "multisensory integration" appears to be pre‐conscious, effortless, and highly efficient. The present experiments examined whether experience could modify this seemingly automatic process. Cats were trained in a localization task in which congruent pairs of auditory‐visual stimuli are normally integrated to enhance detection and orientation/approach performance. Consistent with the results of previous studies, animals more reliably detected and approached cross‐modal pairs than their modality‐specific component stimuli, regardless of whether the pairings were novel or familiar. However, when provided evidence that one of the modality‐specific component stimuli had no value (it was not rewarded) animals ceased integrating it with other cues, and it lost its previous ability to enhance approach behaviors. Cross‐modal pairings involving that stimulus failed to elicit enhanced responses even when the paired stimuli were congruent and mutually informative. However, the stimulus regained its ability to enhance responses when it was associated with reward. This suggests that experience can selectively block access of stimuli (i.e., filter inputs) to the multisensory computation. Because this filtering process results in the loss of useful information, its operation and behavioral consequences are not optimal. Nevertheless, the process can be of substantial value in natural environments, rich in dynamic stimuli, by using experience to minimize the impact of stimuli unlikely to be of biological significance, and reducing the complexity of the problem of matching signals across the senses. [ABSTRACT FROM AUTHOR]

Background—to guide the implementation of patient centricity and engagement in cancer clinical trials (CTs) and to operationalize the Canadianized version of the Clinical Trials Transformation Initiative (C-CTTI) model, the development of a charter was identified by cancer CT stakeholders. Methods—the Canadian Cancer Trial Stakeholder Charter (the Charter) was initiated by Colorectal Cancer Canada (CCC) and developed via the—1—formation of an inclusive working group (WG) that drafted the document using recommendations collected during the development of the C-CTTI model; 2—socialization of the draft Charter to solicit feedback from cancer CT stakeholders, including those who attended the 2019 CCC Conference; and 3—incorporation of stakeholders’ feedback and finalization of the Charter by the WG. Results—the Charter was built around five guiding principles—1—patient centricity; 2—commitment to education and training; 3—collaboration as equal and independent partners in research; 4—transparency and accountability; and 5—high standards in data collection integrity and honesty. These principles led to the Charter’s five tenets, which stipulate stakeholder commitments, aiming to make CTs accessible to all patients, improve the design and implementation of CTs to benefit patients, expand recruitment and retention of patients in CTs, and further advance cancer research and treatment. Conclusions—the Charter is intended to integrate the patient voice into the Canadian cancer CT continuum. The next phases of the C-CTTI model include the adoption and implementation of the Charter, the establishment of a patient group training program, and the development of real-world evidence/real-world data methodologies. [ABSTRACT FROM AUTHOR]

Timely identification of COVID-19 patients at high risk of mortality can significantly improve patient management and resource allocation within hospitals. This study seeks to develop and validate a data-driven personalized mortality risk calculator for hospitalized COVID-19 patients. De-identified data was obtained for 3,927 COVID-19 positive patients from six independent centers, comprising 33 different hospitals. Demographic, clinical, and laboratory variables were collected at hospital admission. The COVID-19 Mortality Risk (CMR) tool was developed using the XGBoost algorithm to predict mortality. Its discrimination performance was subsequently evaluated on three validation cohorts. The derivation cohort of 3,062 patients has an observed mortality rate of 26.84%. Increased age, decreased oxygen saturation (≤ 93%), elevated levels of C-reactive protein (≥ 130 mg/L), blood urea nitrogen (≥ 18 mg/dL), and blood creatinine (≥ 1.2 mg/dL) were identified as primary risk factors, validating clinical findings. The model obtains out-of-sample AUCs of 0.90 (95% CI, 0.87–0.94) on the derivation cohort. In the validation cohorts, the model obtains AUCs of 0.92 (95% CI, 0.88–0.95) on Seville patients, 0.87 (95% CI, 0.84–0.91) on Hellenic COVID-19 Study Group patients, and 0.81 (95% CI, 0.76–0.85) on Hartford Hospital patients. The CMR tool is available as an online application at covidanalytics.io/mortality_calculator and is currently in clinical use. The CMR model leverages machine learning to generate accurate mortality predictions using commonly available clinical features. This is the first risk score trained and validated on a cohort of COVID-19 patients from Europe and the United States. [ABSTRACT FROM AUTHOR]

Background: High-quality surgery is essential for optimal oncologic outcomes in rectal cancer, but total mesorectal excision (TME) can be difficult for mid- and low rectal cancers. Preoperative identification of patients at risk for difficult TME may change the operative approach. The objective of this study was to determine if MRI pelvimetry can predict poor-quality surgery in patients undergoing laparoscopic low anterior resection (LAR) for mid- and low rectal cancer.Methods: All patients undergoing laparoscopic LAR for rectal cancer ≤ 9 cm from the anal verge at a single tertiary care referral center from 2011 to 2017 were retrospectively reviewed. Pelvic dimensions were measured from preoperative staging MRI on sagittal and axial views. Pelvimetry variables were all dichotomized based on median values. Exploratory factor analysis then identified the most relevant variables for regression analysis. The primary outcome was poor-quality resection, defined as an incomplete mesorectal grade, or involved circumferential (CRM) or distal (DRM) resection margins.Results: There were 92 patients included in this study, of which 70% were male, the mean BMI was 26.0 kg/m2, and the mean tumor height was 6.6 cm. Preoperative (chemo)radiotherapy was administered in 70%, and the pathologic T-stage was T3/T4 in 41%. The overall incidence of poor-quality resection was 17%, including 13% incomplete TME, 7% involved CRM, and 1% involved DRM. Factor analysis identified S1-pubic symphysis and the angle between S1 and S5-bottom of symphysis (angle ABD) as relevant variables. After adjusting for pathologic T-stage, BMI, and tumor height, a S1-S5-bottom of symphysis angle > 74.3° (OR 6.19, 95% CI 1.18-32.37) independently predicted poor-quality resection.Conclusions: MRI pelvimetry can identify patients at risk for a poor-quality resection after laparoscopic proctectomy for mid- and low rectal cancer. These patients may benefit from the selective use of more advanced access methods to improve surgical resection quality. [ABSTRACT FROM AUTHOR]

Introduction: Delayed gastrointestinal (GI) recovery remains a significant morbidity after colorectal surgery. Intracorporeal anastomosis for right colectomy may hasten GI recovery. Therefore, the objective of this study was to determine the effect of intracorporeal versus extracorporeal anastomosis on GI recovery after elective laparoscopic right colectomy within an established ERAS program.Methods: Adult patients undergoing elective laparoscopic right colectomy at a single high-volume institution from 07/2014 to 12/2018 were reviewed. Patients were divided into two groups: intracorporeal (IC) and extracorporeal (EC). The primary outcome was time to GI-3 defined as days to tolerance of solid diet and first flatus/bowel movement. Prolonged postoperative ileus (PPOI) was defined as GI-3 not met by postoperative day 4. Secondary outcomes were length of stay (LOS) and overall 30-day complications. Sensitivity analysis was performed using coarsened exact matching to account for unmeasured confounding. Multiple regression was performed using a Cox proportional hazard model to identify predictors of GI recovery.Results: A total of 346 patients were reviewed, of which 226 were included (71IC, 155EC). Patient characteristics were well balanced between groups: mean age was 64.9 years (SD 15.9), BMI was 26.3 (SD 5.7), 38.1% of patients had ASA ≥ 3, and 78.3% underwent surgery for neoplasms. IC anastomosis was associated with longer operative duration (165 min (SD 40); 144 min (SD 48), p = 0.002). There was no difference in the median time to GI-3 (IC 2 days [IQR1-2]; EC 2 days [IQR2-3], p = 0.135). The incidence of PPOI (IC 8.5%; EC 10.3%, p = 0.659), superficial SSI (4.2% vs. 5.8%, p = 0.757), deep SSI (2.8% vs. 5.2%, p = 0.729), and median LOS (3 days [IQR 2-4] vs. 3 [IQR 3-5], p = 0.059) were also similar. On multivariate analysis, IC anastomosis did not independently predict faster GI recovery (HR 0.98, 95% CI 0.71-1.34). Similar results were observed in the matched cohort (185 patients (61IC, 124EC)).Conclusion: In this study, IC anastomosis was not associated with faster GI recovery or reduced complication rate compared to EC anastomosis. Longer term studies may be required to determine the potential benefits of IC anastomosis. [ABSTRACT FROM AUTHOR]

Current stroke risk assessment tools presume the impact of risk factors is linear and cumulative. However, both novel risk factors and their interplay influencing stroke incidence are difficult to reveal using traditional additive models. The goal of this study was to improve upon the established Revised Framingham Stroke Risk Score and design an interactive Non-Linear Stroke Risk Score. Leveraging machine learning algorithms, our work aimed at increasing the accuracy of event prediction and uncovering new relationships in an interpretable fashion. A two-phase approach was used to create our stroke risk prediction score. First, clinical examinations of the Framingham offspring cohort were utilized as the training dataset for the predictive model. Optimal Classification Trees were used to develop a tree-based model to predict 10-year risk of stroke. Unlike classical methods, this algorithm adaptively changes the splits on the independent variables, introducing non-linear interactions among them. Second, the model was validated with a multi-ethnicity cohort from the Boston Medical Center. Our stroke risk score suggests a key dichotomy between patients with history of cardiovascular disease and the rest of the population. While it agrees with known findings, it also identified 23 unique stroke risk profiles and highlighted new non-linear relationships; such as the role of T-wave abnormality on electrocardiography and hematocrit levels in a patient's risk profile. Our results suggested that the non-linear approach significantly improves upon the baseline in the c-statistic (training 87.43% (CI 0.85–0.90) vs. 73.74% (CI 0.70–0.76); validation 75.29% (CI 0.74–0.76) vs 65.93% (CI 0.64–0.67), even in multi-ethnicity populations. The clinical implications of the new risk score include prioritization of risk factor modification and personalized care at the patient level with improved targeting of interventions for stroke prevention. [ABSTRACT FROM AUTHOR]

Here, flexible nanocomposites based on reduced graphene oxide (RGO) and commercial elastomers such as poly (acrylonitrile-ran-butadiene) (PANB) and poly (styrene-block-isoprene-block-styrene) (SIS) have been developed with enhanced electrical and mechanical properties due to the RGO fine dispersion. The RGO incorporation via stepwise addition resulted in well-dispersed RGO platelets in all polymer matrices. This allowed us to attain a comparatively low percolation threshold concentration (4.2 wt.% for all nanocomposites), at which the conductivity and current flow through the nanocomposites appreciably increased. The nanocomposite conductivity further increased with the increase of the RGO loading independently of the polymer type (PANB or SIS) or PANB molecular weight and acrylonitrile content. The highest conductivities obtained in this work are in the range 7.5–8.0 × 10–5 S/cm. Mechanical properties measured for SIS and PANB nanocomposites showed that tensile strength increases (in the case of SIS, by a factor of three) with the increase of the RGO content most likely due to physical crosslinking of the polymer with RGO. Improved electrical and mechanical properties of these nanocomposites make them promising as microwave absorbers or antistatic coatings. [ABSTRACT FROM AUTHOR]

Although the ability to integrate information across the senses is compromised in some individuals for unknown reasons, similar defects have been observed when animals are reared without multisensory experience. The experience-dependent development of multisensory integration has been studied most extensively using the visual-auditory neuron of the cat superior colliculus (SC) as a neural model. In the normally-developed adult, SC neurons react to concordant visual-auditory stimuli by integrating their inputs in real-time to produce non-linearly amplified multisensory responses. However, when prevented from gathering visual-auditory experience, their multisensory responses are no more robust than their responses to the individual component stimuli. The mechanisms operating in this defective state are poorly understood. Here we examined the responses of SC neurons in "naïve" (i.e., dark-reared) and "neurotypic" (i.e., normally-reared) animals on a millisecond-by-millisecond basis to determine whether multisensory experience changes the operation by which unisensory signals are converted into multisensory outputs (the "multisensory transform"), or whether it changes the dynamics of the unisensory inputs to that transform (e.g., their synchronization and/or alignment). The results reveal that the major impact of experience was on the multisensory transform itself. Whereas neurotypic multisensory responses exhibited non-linear amplification near their onset followed by linear amplification thereafter, the naive responses showed no integration in the initial phase of the response and a computation consistent with competition in its later phases. The results suggest that multisensory experience creates an entirely new computation by which convergent unisensory inputs are used cooperatively to enhance the physiological salience of cross-modal events and thereby facilitate normal perception and behavior. [ABSTRACT FROM AUTHOR]

Background: Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment.Methods: The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores.Results: The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results.Conclusions: Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care. [ABSTRACT FROM AUTHOR]

Background: Increased adherence with enhanced recovery pathways (ERP) is associated with improved outcomes. However, adherence to postoperative elements that rely on patient participation remains suboptimal. Mobile device apps may improve delivery of health education material and have the potential to foster behavior change and improve patient compliance. The objective of this study was to estimate the extent to which a novel mobile device app affects adherence to an ERP for colorectal surgery in comparison to standard written education.Methods: This was a superiority, parallel-group, assessor-blind, sham-controlled randomized trial involving 97 patients undergoing colorectal resection. Participants were randomly assigned with a 1:1 ratio into one of two groups: (1) iPad including a novel mobile device app for postoperative education and self-assessment of recovery, or (2) iPad without the app. The primary outcome measure was mean adherence (%) to a bundle of five postoperative ERP elements requiring patient participation: mobilization, gastrointestinal motility stimulation, breathing exercises, and consumption of oral liquids and nutritional drinks.Results: In the intervention group, app usage was high (94% completed surveys on POD0, 82% on POD1, 72% on POD2). Mean overall adherence to the bundle on the two first postoperative days was similar between groups: 59% (95% CI 52-66%) in the intervention group and 62% (95% CI 56-68%) in the control group [Adjusted mean difference 2.4% (95% CI - 5 to 10%) p = 0.53].Conclusions: In this randomized trial, access to a mobile health application did not improve adherence to a well-established enhanced recovery pathway in colorectal surgery patients, when compared to standard written patient education. Future research should evaluate the impact of applications integrating novel behavioral change techniques, particularly in contexts where adherence is low. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend incorporation of more than 20 perioperative interventions within an enhanced recovery program (ERP). However, the impact of overall adherence to the pathway and the relative contribution of each intervention are unclear. The aim of this study was to estimate the extent to which adherence to ERP elements is associated with outcomes and identify key ERP elements predicting successful recovery following bowel resection.Methods: Prospectively collected data entered in a registry specifically designed for ERPs were reviewed. Patients undergoing elective bowel resection between 2012 and 2014 were treated within an ERP comprising 23 care elements. Primary outcome was successful recovery defined as the absence of complications, discharge by postoperative day 4 and no readmission. Secondary outcomes were length of hospital stay (LOS), 30-day morbidity, and severity (Comprehensive complication index, CCI, 0-100). Regression analyses were adjusted for potential confounders.Results: A total of 347 patients were included in the study. Median primary LOS was 4 days (IQR 3-7). Patients were adherent to median 18 (IQR 16-20) elements. A total of 156 (45 %) patients had successful recovery. Morbidity occurred in 175 (50 %) patients with median CCI 8.6 (IQR 0-22.6). There was a positive association between adherence and successful recovery (OR 1.39 for every additional element, p < 0.001), LOS (11 % reduction for every additional element, p < 0.001), 30-day postoperative morbidity (OR 0.78, p < 0.001), and the CCI (17 % reduction, p < 0.001). Laparoscopy (OR 4.32, p < 0.001), early mobilization out of bed (OR 2.25, p = 0.021), and early termination of IV fluid infusion (OR 2.00, p = 0.013) significantly predicted successful recovery. These factors were also associated with reduced morbidity and complication severity.Conclusions: Increased adherence to ERP interventions was associated with successful early recovery and a reduction in postoperative morbidity and complication severity. In an established ERP where overall adherence was high, laparoscopic approach, perioperative fluid management, and patient mobilization remain key elements associated with improved outcomes. [ABSTRACT FROM AUTHOR]

Hemianopia is characterized by blindness in one half of the visual field and is a common consequence of stroke and unilateral injury to the visual cortex. There are few effective rehabilitative strategies that can relieve it. Using the cat as an animal model of hemianopia, we found that blindness induced by lesions targeting all contiguous areas of the visual cortex could be rapidly reversed by a non-invasive, multisensory (auditory-visual) exposure procedure even while animals were anesthetized. Surprisingly few trials were required to reinstate vision in the previously blind hemisphere. That rehabilitation was possible under anesthesia indicates that the visuomotor behaviors commonly believed to be essential are not required for this recovery, nor are factors such as attention, motivation, reward, or the various other cognitive features that are generally thought to facilitate neuro-rehabilitative therapies. [ABSTRACT FROM AUTHOR]

The operation of our multiple and distinct sensory systems has long captured the interest of researchers from multiple disciplines. When the Society was founded 50 years ago to bring neuroscience research under a common banner, sensory research was largely divided along modalityspecific lines. At the time, there were only a few physiological and anatomical observations of the multisensory interactions that powerfully influence our everyday perception. Since then, the neuroscientific study of multisensory integration has increased exponentially in both volume and diversity. From initial studies identifying the overlapping receptive fields of multisensory neurons, to subsequent studies of the spatial and temporal principles that govern the integration of multiple sensory cues, our understanding of this phenomenon at the single-neuron level has expanded to include a variety of dimensions. We now can appreciate how multisensory integration can alter patterns of neural activity in time, and even coordinate activity among populations of neurons across different brain areas. There is now a growing battery of sophisticated empirical and computational techniques that are being used to study this process in a number of models. These advancements have not only enhanced our understanding of this remarkable process in the normal adult brain, but also its underlying circuitry, requirements for development, susceptibility to malfunction, and how its principles may be used to mitigate malfunction. [ABSTRACT FROM AUTHOR]

Introduction: Treatment delay may have detrimental effects on cancer outcomes. The impact of longer delays on colorectal cancer outcomes remains poorly described. The objective of this study was to determine the effect of delays to curative-intent surgical resection on survival in colorectal cancer patients.Methods: All adult patients undergoing elective resection of primary non-metastatic colorectal adenocarcinoma from January 2009 to December 2014 were reviewed. Treatment delays were defined as the time from tissue diagnosis to definitive surgery, categorized as < 4, 4 to < 8, and ≥ 8 weeks. Primary outcomes were 5-year disease-free (DFS) and overall survival (OS). Statistical analysis included Kaplan-Meier curves and Cox regression models.Results: A total of 408 patients were included (83.2% colon;15.8% rectal) with a mean follow-up of 58.4 months (SD29.9). Fourteen percent (14.0%) of patients underwent resection < 4 weeks, 40.0% 4 to < 8 weeks, and 46.1% ≥ 8 weeks. More rectal cancer patients had treatment delay ≥ 8 weeks compared with colonic tumors (69.8% vs. 41.4%, p < 0.001). Cumulative 5-year DFS and OS were similar between groups (p = 0.558; p = 0.572). After adjusting for confounders, surgical delays were not independently associated with DFS and OS.Conclusions: Treatment delays > 4 weeks were not associated with worse oncologic outcomes. Delaying surgery to optimize patients can safely be considered without compromising survival. [ABSTRACT FROM AUTHOR]

Unilateral lesions of visual cortex have the secondary consequence of suppressing visual circuits in the midbrain superior colliculus (SC), collectively producing blindness in contralesional space ("hemianopia"). Recent studies have demonstrated that SC visual responses and contralesional vision can be reinstated by a non‐invasive multisensory training procedure in which spatiotemporally concordant visual‐auditory pairs are repeatedly presented within the blind hemifield. Despite this recovery of visual responsiveness, the loss of visual cortex was expected to result in permanent deficits in that hemifield, especially when visual events in both hemifields compete for attention and access to the brain's visuomotor circuitry. This was evaluated in the present study in a visual choice paradigm in which the two visual hemifields of recovered cats were simultaneously stimulated with equally valent visual targets. Surprisingly, the expected disparity was not found, and some animals even preferred stimuli presented in the previously blind hemifield. This preference persisted across multiple stimulus intensity levels and there was no indication that animals were less aware of cues in the previously blind hemifield than in its spared counterpart. Furthermore, when auditory cues were combined with visual cues, the enhanced performance they produced on a visual task was no greater in the normal than in the previously blind hemifield. These observations suggest that the multisensory rehabilitation paradigm revealed greater inherent visual information processing potential in the previously blind hemifield than was believed possible given the loss of visual cortex. [ABSTRACT FROM AUTHOR]

Introduction: Patient-reported outcome measures (PROMs) are pivotal to promote patient-centered perioperative care. Adherence to enhanced recovery programs (ERPs) is associated with improved clinical outcomes (i.e., morbidity, length of stay), but the impact of adherence on PROMs is uncertain. The objective of this study was to evaluate the extent to which adherence to an ERP for colorectal surgery is associated with postoperative recovery as assessed using PROMs.Methods and Procedures: 100 patients were included [median age 63 (IQR 50-71) years, 81 laparoscopic, 37 rectal surgery]. Overall adherence to the ERP and adherence to specific ERP elements were analyzed. Adjusted linear regression was used to evaluate the association of adherence with PROMs assessing early recovery [Abdominal surgery impact scale (ASIS) and Multidimensional fatigue inventory (MFI) on POD2] and late recovery (Duke Activity Status Index, RAND-36 Physical and Mental Summary Scores, Life-Space Mobility Assessment at 4 weeks after surgery). Missing data were addressed using multiple imputations.Results: Median adherence to the ERP was 80% (16/20 elements, IQR 70-90%). Overall adherence was associated with ASIS scores on POD2 (4% increase per additional element, 95% CI 1-8%; p = 0.018). When specific ERP elements were analyzed, ASIS scores were associated with adherence to PONV prophylaxis (34% increase, 95% CI 5-63%; p = 0.023) and early solid food diet (20% increase, 95% CI 5-35%; p = 0.009). MFI General fatigue and MFI Mental fatigue scores on POD2 were associated with adherence to PONV prophylaxis (36% decrease, 95% CI - 64 to - 8%, p = 0.014 and 22% decrease, 95% CI - 44 to - 8%, p = 0.042). Overall adherence and adherence to specific elements were not associated with PROMs at 4 weeks after surgery.Conclusion: Our findings suggest that, from the perspective of patients, adherence to an ERP for colorectal surgery impacts early, but not late postoperative recovery. This result may reflect the lack of PROMs able to validly measure postoperative recovery beyond hospital discharge. [ABSTRACT FROM AUTHOR]

Background: Prolonged postoperative ileus (PPOI) is common after colorectal surgery but has not been widely studied in the context of enhanced recovery pathways (ERPs) that include interventions aimed to accelerate gastrointestinal recovery. The aim of this study is to estimate the incidence and predictors of PPOI in the context of an ERP for colorectal surgery.Methods: We analyzed data from an institutional colorectal surgery ERP registry. Incidence of PPOI was estimated according to a definition adapted from Vather (intolerance of solid food and absence of flatus or bowel movement for ≥ 4 days) and compared to other definitions in the literature. Potential risk factors for PPOI were identified from previous studies, and their predictive ability was evaluated using Bayesian model averaging (BMA). Results are presented as posterior effect probability (PEP). Evidence of association was categorized as: no evidence (PEP < 50%), weak evidence (50-75%), positive evidence (75-95%), strong evidence (95-99%), and very strong evidence (> 99%).Results: There were 323 patients analyzed (mean age 63.5 years, 51% males, 74% laparoscopic, 33% rectal resection). The incidence of PPOI was 19% according to the primary definition, but varied between 11 and 59% when using other definitions. On BMA analysis, intraoperative blood loss (PEP 99%; very strong evidence), administration of any intravenous opioids in the first 48 h (PEP 94%; strong evidence), postoperative epidural analgesia (PEP 56%; weak evidence), and non-compliance with intra-operative fluid management protocols (3 ml/kg/h for laparoscopic and 5 ml/kg/h for open; PEP 55%, weak evidence) were predictors of PPOI.Conclusions: The incidence of PPOI after colorectal surgery is high even within an established ERP and varied considerably by diagnostic criteria, highlighting the need for a consensus definition. The use of intravenous opioids is a modifiable strong predictor of PPOI within an ERP, while the role of epidural analgesia and intraoperative fluid management should be further evaluated. [ABSTRACT FROM AUTHOR]

Background: Poor functional capacity (FC) is an independent predictor of postoperative morbidity. However, there is still a lack of evidence as to whether enhancing FC before surgery has a protective effect on postoperative complications. The purpose of this study was to determine whether an improvement in preoperative FC impacted positively on surgical morbidity. Methods: This was a secondary analysis of a cohort of patients who underwent colorectal resection for cancer under Enhanced Recovery After Surgery care. FC was assessed with the 6-min walk test, which measures the distance walked in 6 min (6MWD), at 4 weeks before surgery and again the day before. The study population was classified into two groups depending on whether participants achieved a significant improvement in FC preoperatively (defined as a preoperative 6MWD change ≥19 meters) or not (6MWD change <19 meters). The primary outcome measure was 30-d postoperative complications, assessed with the Comprehensive Complication Index (CCI). The association between improved preoperative FC and severe postoperative complication was evaluated using multivariable logistic regression. Results: A total of 179 eligible adults were studied: 80 (44.7%) improved in 6MWD by ≥19 m preoperatively, and 99 (55.3%) did not. Subjects whose FC increased had lower CCI (0 [0–8.7] versus 8.7 [0–22.6], p =.022). Furthermore, they were less likely to have a severe complication (adjusted OR 0.28 (95% CI 0.11–0.74), p =.010), and to have an ED visit. Conclusion: Improved preoperative FC was independently associated with a lower risk of severe postoperative complications. Further investigation is required to establish a causative relationship conclusively. [ABSTRACT FROM AUTHOR]

Mature multisensory superior colliculus (SC) neurons integrate information across the senses to enhance their responses to spatiotemporally congruent cross-modal stimuli. The development of this neurotypic feature of SC neurons requires experience with cross-modal cues. In the absence of such experience the response of an SC neuron to congruent cross-modal cues is no more robust than its response to the most effective component cue. This "default" or "naive" state is believed to be one in which cross-modal signals do not interact. The present results challenge this characterization by identifying interactions between visual-auditory signals in male and female cats reared without visual-auditory experience. By manipulating the relative effectiveness of the visual and auditory cross-modal cues that were presented to each of these naive neurons, an active competition between cross-modal signals was revealed. Although contrary to current expectations, this result is explained by a neuro-computational model in which the default interaction is mutual inhibition. These findings suggest that multisensory neurons at all maturational stages are capable of some form of multisensory integration, and use experience with cross-modal stimuli to transition from their initial state of competition to their mature state of cooperation. By doing so, they develop the ability to enhance the physiological salience of cross-modal events thereby increasing their impact on the sensorimotor circuitry of the SC, and the likelihood that biologically significant events will elicit SC-mediated overt behaviors. [ABSTRACT FROM AUTHOR]

Background: Complete mesocolic excision (CME) is advocated based on oncologic superiority, but not commonly performed in North America. Many data are case series with few comparative studies. Our aim was to perform a systematic review comparing outcomes between CME and non-CME colectomy.Methods: A systematic review was performed according to PRISMA guidelines of MEDLINE, EMBASE, HealthStar, Web of Science, and Cochrane Library. Studies were included if they compared conventional resection (non-CME) to CME for colon cancer. Quality was assessed using methodological index for non-randomized studies (MINORS). The main outcome measures were short-term morbidity and oncologic outcomes. Weighted pooled means and proportions with 95% CI were calculated using a random-effects model when appropriate.Results: Out of 825 unique citations, 23 studies underwent full-text reviews and 14 met inclusion criteria. Mean MINORS score was 13.3 (range 11-15). The mean sample size in CME group was 1166 (range 45-3756) and 945 (range 40-3425) in non-CME. Four papers reported plane of dissection, with CME plane achieved in 85.8% (95% CI 79.8-91.7). Mean OR time in CME group was 167 min (163-171) and 138 min (135-142) in conventional group. Perioperative morbidity was reported in six studies, with pooled overall complications of 22.5% (95% CI 18.4-26.6) for CME and 19.6 (95% CI 13.6-25.5) for non-CME. Anastomotic leak occurred in 6.0% (95% CI 2.2-9.7) of CME resections versus 6.0% (95% CI 4.1-7.9) in non-CME. CME had more lymph nodes, longer distance to high tie, and specimen length in all studies. Nine studies compared long-term oncologic outcomes and only three reported statistically significant higher disease-free or overall survival in favor of CME. Local recurrence was lower after CME in two of four studies.Conclusions: The quality of evidence is limited and does not consistently support the superiority of CME. Better data are needed before CME can be recommended as the standard of care for colon cancer resections. [ABSTRACT FROM AUTHOR]

Background: The short-term benefits of laparoscopy for rectal surgery are equivocal. The objective of this study was to determine the clinical and economic impact of an enhanced recovery pathway (ERP) for laparoscopic and open rectal surgery.Materials and Methods: All patients who underwent elective rectal resection with primary anastomosis between January 2009 and March 2012 at two tertiary-care, university-affiliated institutions were identified. Patients who met inclusion criteria were divided into four groups, according to surgical approach (laparoscopic [lap] or open) and perioperative management (ERP or conventional care [CC]). Length of stay (LOS), postoperative complications, and hospital costs were compared.Results: A total of 381 patients were included in the analysis (201 open-CC, 34 lap-CC, 38 open-ERP, and 108 lap-ERP). Patients were mostly similar at baseline. ERPs significantly reduced median LOS after both open cases (open-CC 10 days versus open-ERP 7.5 days, P = .003) and laparoscopic cases (lap-CC 5 days versus lap-ERP 4.5 days, P = .046). ERPs also reduced variability in LOS compared with CC. There was no difference in postoperative complications with the use of ERPs (open-CC 51% versus open-ERP 50%, P = .419; lap-CC 32% versus lap-ERP 36%, P = .689). On multivariate analysis, both ERP (-3.6 days [95% confidence interval, CI -6.0 to -1.3]) and laparoscopy (-3.6 days [95% CI -5.9 to -1.0]) were independently associated with decreased LOS. Overall costs were only lower when lap-ERP was compared with open-CC (mean difference -2420 CAN$ [95% CI -5628 to -786]).Conclusions: ERPs reduced LOS after rectal resections, and the combination of laparoscopy and ERPs significantly reduced overall costs compared to when neither strategy was used. [ABSTRACT FROM AUTHOR]

Introduction: While patient engagement and clinical audit are key components of successful enhanced recovery programs (ERPs), they require substantial resource allocation. The objective of this study was to assess the validity and usability of a novel mobile device application for education and self-reporting of adherence for patients undergoing bowel surgery within an established ERP.Methods: Prospectively recruited patients undergoing bowel surgery within an ERP used a novel app specifically designed to provide daily recovery milestones and record adherence to 15 different ERP processes and six patient-reported outcomes (PROs). Validity was measured by the agreement index (Cohen's kappa coefficient for categorical, and interclass correlation coefficient (ICC) for continuous variables) between patient-reported data through the app and data recorded by a clinical auditor. Acceptability and usability of the app were measured by the System Usability Scale (SUS).Results: Forty-five patients participated in the study (mean age 61, 64% male). Overall, patients completed 159 of 179 (89%) of the available questionnaires through the app. Median time to complete a questionnaire was 2 min 49 s (i.q.r. 2'32″-4'36″). Substantial (kappa > 0.6) or almost perfect agreement (kappa > 0.8) and strong correlation (ICC > 0.7) between data collected through the app and by the clinical auditor was found for 14 ERP processes and four PROs. Patient-reported usability was high; mean SUS score was 87 (95% CI 83-91). Only 6 (13%) patients needed technical support to use the app. Forty (89%) patients found the app was helpful to achieve their daily goals, and 34 (76%) thought it increased their motivation to recover after surgery.Conclusions: This novel application provides a tool to record patient adherence to care processes and PROs, with high agreement with traditional clinical audit, high usability, and patient satisfaction. Future studies should investigate the use of mobile device apps as strategies to increase adherence to perioperative interventions. [ABSTRACT FROM AUTHOR]

The ability to integrate information across multiple senses enhances the brain’s ability to detect, localize, and identify external events. This process has been well documented in single neurons in the superior colliculus (SC), which synthesize concordant combinations of visual, auditory, and/or somatosensory signals to enhance the vigor of their responses. This increases the physiological salience of crossmodal events and, in turn, the speed and accuracy of SC-mediated behavioral responses to them. However, this capability is not an innate feature of the circuit and only develops postnatally alter the animal acquires sufficient experience with covariant crossmodal events to form links between their modality-specific components. Of critical importance in this process are tectopetal influences from association cortex. Recent findings suggest that, despite its intuitive appeal, a simple generic associative rule cannot explain how this circuit develops its ability to integrate those crossmodal inputs to produce enhanced multisensory responses. The present neurocomputational model explains how this development can be understood as a transition from a default state in which crossmodal SC inputs interact competitively to one in which they interact cooperatively. Crucial to this transition is the operation of a learning rule requiring coactivation among tectopetal afferents for engagement. The model successfully replicates findings of multisensory development in normal cats and cats of either sex reared with special experience. In doing so, it explains how the cortico-SC projections can use crossmodal experience to craft the multisensory integration capabilities of the SC and adapt them to the environment in which they will be used. [ABSTRACT FROM AUTHOR]