Formal mentorship in Canadian radiology residency programmes.

AIM: To characterise formal mentorship programmes in Canadian radiology residency programmes, to evaluate residents' perspectives on formal mentorship, and to identify ways to optimise mentorship during radiology training. MATERIALS AND METHODS: An anonymous survey was distributed to radiology resident representatives of the Canadian Association of Radiologists (CAR) Resident and Fellow Section (RFS). Questions pertained to the presence and structure of formal mentorship programmes at each participant's institution. RESULTS: The survey was distributed to 33 radiology residents, of which 30 responded. All 16 accredited radiology residency programmes in Canada were represented. Of these programmes, 12 (75%) had formal mentorship programmes and four (25%) did not. The structure of formal mentorship programmes varied among institutions including one-on-one and group mentoring. For 33% of residency programmes, the programme director assigned the mentor and mentee groups. Only 33% of respondents had the option of choosing their mentor. Lack of funding and lack of time were the two main perceived barriers by residents to maintaining mentorship relationships. CONCLUSION: Although not all radiology residency programmes in Canada have a formal mentorship programme, most have a form of structured mentorship in place. As formal mentorship programmes improve overall mentorship experience during residency, they can lead to improved research productivity, fellowship, and career preparation, as well as work-life balance for Canadian radiology residents.

A Canadian cancer trials group phase IB study of durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4) given concurrently or sequentially in patients with advanced, incurable solid malignancies.

Background The IND.226 study was a phase Ib study to determine the recommended phase II dose of durvalumab + tremelimumab in combination with standard platinum-doublet chemotherapy. Sequential administration of multiple agents increases total chair time adding costs overall and inconvenience for patients. This cohort of the IND.226 study evaluated the safety and tolerability of durvalumab + tremelimumab given either sequentially (SEQ) or concurrently (CON). Methods Patients with advanced solid tumours were enrolled and randomised to either SEQ tremelimumab 75 mg IV over 1 h followed by durvalumab 1500 mg IV over 1 h q4wks on the same day, or CON administration over 1 h. The serum pharmacokinetic profile of SEQ versus CON of durvalumab and tremelimumab administration was also evaluated. Results 14 patients either received SEQ (n = 7pts) or CON (n = 7 pts). There were no infusion related reactions. Drug related adverse events (AEs) were mainly low grade and manageable, and comparable in frequency between SEQ/CON- fatigue (43%/57%), rash (43%/43%), pruritus (43%/29%) and nausea (14%/29%). One patient in each cohort discontinued treatment due to toxicity. The PK profiles of durvalumab and tremelimumab were similar between CON and SEQ, and to historical reference data. Conclusions Concurrent administration of durvalumab and tremelimumab over 1 h is safe with a comparable PK profile to sequential administration.

Predictors of sling revision after mid-urethral sling procedures: a case-control study.

OBJECTIVE: To identify patient characteristics and surgical factors predictive of complications requiring mid-urethral sling (MUS) revision/removal. DESIGN: Case-control study. SETTING: Tertiary academic centre in Canada. POPULATION: One hundred and seven women undergoing MUS revision/removal between 2005 and 2016 were matched with 214 controls by date of index MUS procedure (2:1 ratio). METHODS: Data on patient and surgical factors were obtained via manual electronic and paper chart review. Three sets of pre-specified simple and multivariable logistic regression models were fitted to: (1) examine previously reported risk factors for MUS revision after primary surgical treatment; (2) identify preoperative predictors of MUS complications requiring revision/removal; and (3) identify surgical factors associated with this outcome after adjusting for potential confounding factors. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) for patient and surgical factors. RESULTS: The median time to MUS revision was 153 days (interquartile range, IQR 49-432 days). Active smoking status (OR 2.29, 95% CI 1.13-4.63, P = 0.03), having had a previous hysterectomy (OR 3.88, 95% CI 2.02-7.46, P < 0.01), and undergoing concomitant pelvic organ prolapse surgery at the time of the index MUS procedure (OR 2.63, 95% CI 1.32-5.52, P < 0.01) were independently associated with the need for MUS revision/removal. Sling type (obturator versus retropubic), method of tensioning (to cough versus over instrument), anaesthetic type, and estimated blood loss were not associated with this outcome in the analysis presented here. CONCLUSIONS: Active smoking status, having had a previous hysterectomy, and undergoing concomitant surgery for pelvic organ prolapse are risk factors for requiring subsequent MUS revision/removal. TWEETABLE ABSTRACT: Risk factors for sling revision include smoking, previous hysterectomy, and concomitant prolapse surgery.

A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer.

BACKGROUND: The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. PATIENTS AND METHODS: This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. RESULTS: In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. CONCLUSIONS: Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.

Expertise for cars and birds recruits brain areas involved in face recognition.

Expertise with unfamiliar objects ('greebles') recruits face-selective areas in the fusiform gyrus (FFA) and occipital lobe (OFA). Here we extend this finding to other homogeneous categories. Bird and car experts were tested with functional magnetic resonance imaging during tasks with faces, familiar objects, cars and birds. Homogeneous categories activated the FFA more than familiar objects. Moreover, the right FFA and OFA showed significant expertise effects. An independent behavioral test of expertise predicted relative activation in the right FFA for birds versus cars within each group. The results suggest that level of categorization and expertise, rather than superficial properties of objects, determine the specialization of the FFA.

Activation of the middle fusiform 'face area' increases with expertise in recognizing novel objects.

Part of the ventral temporal lobe is thought to be critical for face perception, but what determines this specialization remains unknown. We present evidence that expertise recruits the fusiform gyrus 'face area'. Functional magnetic resonance imaging (fMRI) was used to measure changes associated with increasing expertise in brain areas selected for their face preference. Acquisition of expertise with novel objects (greebles) led to increased activation in the right hemisphere face areas for matching of upright greebles as compared to matching inverted greebles. The same areas were also more activated in experts than in novices during passive viewing of greebles. Expertise seems to be one factor that leads to specialization in the face area.

Visual priming: the ups and downs of familiarity.

A dynamic picture of the neural processes underlying the 'priming' effects on the visual system of repeated object presentation has been obtained by combining functional magnetic resonance imaging with a gradual 'unmasking' procedure that slows down the process of visual recognition.

Levels of categorization in visual recognition studied using functional magnetic resonance imaging.

BACKGROUND: Recent functional neuroimaging results implicate part of the ventral temporal lobe of the brain in face recognition, and have, together with neurophysiological findings, been used as evidence for a face-specific neural module in the brain. Experimental designs, however, have often failed to distinguish between the class of the object used as the stimulus (face or non-face) and the level of categorization at which the stimulus is recognized (the 'basic' level, such as 'bird', at which familiar objects are first recognized, or more subordinate levels - 'sparrow', for example - which require additional perceptual processing). We have used echo-planar functional magnetic resonance imaging to compare brain activation for the matching of non-face objects with subordinate-level and basic-level descriptors. RESULTS: The additional visual processing required to verify the subordinate level of a picture over its basic level was associated with activation of the fusiform and inferior temporal gyri (FIT) as well as the temporal poles. These areas correspond closely to those previously implicated in the processing of facial images. CONCLUSIONS: Our results indicate that areas of the ventral visual pathway that have been associated with face recognition are sensitive to manipulations of the categorization level of non-face objects. This idea offers an alternative to the dominant view that FIT may be organized according to conceptual categories, and our results establish the importance of manipulating task requirements when evaluating a 'neural module' hypothesis.

Impact of hemoglobin levels on outcomes of adjuvant chemotherapy in resected non-small cell lung cancer: the JBR.10 trial experience.

BACKGROUND: Cisplatin-induced anemia may correlate with adverse events, poor quality of life (QoL), decreased adjuvant chemotherapy (ACT) dose intensity, shorter relapse-free survival (RFS) or overall survival (OS). METHODS: The JBR.10 trial demonstrated significantly longer survival with adjuvant cisplatin and vinorelbine (n=242) compared to observation (n=240) in patients with resected NSCLC [Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352(25):2640-2]. This exploratory analysis evaluates the predictive value of baseline (in all patients) and during-treatment (in ACT arm only) hemoglobin (Hb) levels on OS and RFS when adjusted for prognostic factors. Baseline (in all patients) and during treatment (in ACT arm only) Hb levels were also correlated with adverse events, QoL, morbidity and ACT dose intensity. RESULTS: Baseline Hb did not predict RFS or OS. However, there was a trend to shorter OS (p=0.1) when baseline Hb was <120g/L. Lower baseline Hb predicted increased hospitalization (p=0.04) and worse QoL (SOB item, p=0.03) but had no impact on adverse events or dose intensity. There was a trend to longer RFS (p=0.08) in patients with lower nadir during-treatment Hb and to longer OS (p=0.06) and RFS (p=0.08) in patients with maximum during-treatment Hb drop >30% that was not maintained when ACT dose intensity was included in the model. Maximum during-treatment Hb drop >30% correlated with increased lethargy (p=0.003) and worse QoL (fatigue item, p=0.07). CONCLUSIONS: Lower baseline and during-treatment Hb levels seem associated with poorer QoL, fatigue and increased hospitalization. There is a trend for shorter OS in patients with lower baseline Hb levels.

The development of face expertise.

Recent neuroimaging studies in adults indicate that visual areas selective for recognition of faces can be recruited through expertise for nonface objects. This reflects a new emphasis on experience in theories of visual specialization. In addition, novel work infers differences between categories of nonface objects, allowing a re-interpretation of differences seen between recognition of faces and objects. Whether there are experience-independent precursors of face expertise remains unclear; indeed, parallels between literature for infants and adults suggest that methodological issues need to be addressed before strong conclusions can be drawn regarding the origins of face recognition.

A phase I, first in man study of OSI-7836 in patients with advanced refractory solid tumors: IND.147, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, tolerability, toxicity profile, dose-limiting toxicities (DLTs), anti-tumor activity and pharmacokinetics of OSI-7836 given IV on day 1 and day 8 every 3 weeks in patients with advanced incurable cancer. METHODS: Twenty-seven previously treated patients with advanced or metastatic solid tumors were enrolled in this phase I study conducted by the National Cancer Institute of Canada Clinical Trial Group (NCIC CTG). OSI-7836 was administered IV on day 1 and day 8 every 3 weeks. The dose was initially escalated from 100 to 600 mg/m2 and finally de-escalated to 200 mg/m2 in seven cohorts of patients. Patients were evaluated every other cycle of treatment for radiological response. Pharmacokinetics were performed on day 1 and day 8 of cycle 1 for all patients. RESULTS: Twenty-six patients were evaluable for toxicity. All patients experienced reversible Grade 3 lymphopenia beginning at cycle 1. The maximal delivered dose was 600 mg/m2. MTD was reached at 400 mg/m2. DLTs included fever, fatigue, rash, herpes simplex infection, nausea and vomiting. The RP2D was 200 mg/m2. No objective responses were seen in 21 evaluable patients. Pharmacokinetics were dose proportional, with a mean half-life of 46.0 min and a clearance of 34 l/(h.m2). CONCLUSION: OSI-7836 given at 200 mg/m2 on day 1 and day 8 every 3 weekly is associated with manageable toxicity and is recommended for further study. While no objective responses were seen, the significant treatment related lymphopenia suggests that hematologic malignancies may warrant further investigation.

Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome.

BACKGROUND: Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). METHOD: We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group ] [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. RESULTS: In the first set of comparisons, we found significant task x group interactions for the size of activation in the right fusiform gyrus (FG) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. CONCLUSIONS: Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.

Do viewpoint-dependent mechanisms generalize across members of a class?

Evidence for viewpoint-specific image-based object representations have been collected almost entirely using exemplar-specific recognition tasks. Recent results, however, implicate image-based processes in more categorical tasks, for instance when objects contain qualitatively different 3D parts. Although such discriminations approximate class-level recognition. they do not establish whether image-based representations can support generalization across members of an object class. This issue is critical to any theory of recognition, in that one hallmark of human visual competence is the ability to recognize unfamiliar instances of a familiar class. The present study addresses this questions by testing whether viewpoint-specific representations for some members of a class facilitate the recognition of other members of that class. Experiment 1 demonstrates that familiarity with several members of a class of novel 3D objects generalizes in a viewpoint-dependent manner to cohort objects from the same class. Experiment 2 demonstrates that this generalization is based on the degree of familiarity and the degree of geometrical distinctiveness for particular viewpoints. Experiment 3 demonstrates that this generalization is restricted to visually-similar objects rather than all objects learned in a given context. These results support the hypothesis that image-based representations are viewpoint dependent, but that these representations generalize across members of perceptually-defined classes. More generally, these results provide evidence for a new approach to image-based recognition in which object classes are represented as cluster of visually-similar viewpoint-specific representations.

The N170 occipito-temporal component is delayed and enhanced to inverted faces but not to inverted objects: an electrophysiological account of face-specific processes in the human brain.

Behavioral studies have shown that picture-plane inversion impacts face and object recognition differently, thereby suggesting face-specific processing mechanisms in the human brain. Here we used event-related potentials to investigate the time course of this behavioral inversion effect in both faces and novel objects. ERPs were recorded for 14 subjects presented with upright and inverted visual categories, including human faces and novel objects (Greebles). A N170 was obtained for all categories of stimuli, including Greebles. However, only inverted faces delayed and enhanced N170 (bilaterally). These observations indicate that the N170 is not specific to faces, as has been previously claimed. In addition, the amplitude difference between faces and objects does not reflect face-specific mechanisms since it can be smaller than between non-face object categories. There do exist some early differences in the time-course of categorization for faces and non-faces across inversion. This may be attributed either to stimulus category per se (e.g. face-specific mechanisms) or to differences in the level of expertise between these categories.

Drug-food interactions in hospitalised patients. Methods of prevention.

Drug-food interactions in hospitalised patients may result in decreased drug efficacy or increased drug toxicity. The increasing complexity of drug therapy regimens has increased the potential for drug-food interactions to occur, reinforcing the need to develop methods to prevent clinically significant drug-food interactions. Before selecting the optimal method, in terms of feasibility of implementation and successful outcome, drugs with the potential for clinically significant interactions with food must be identified. From an analysis of the literature, 6 methods to prevent drug-food interactions have been suggested as useful tools. Each method has its own advantages and disadvantages. Most have been developed in response to guidelines from the most well recognised agency for quality review in the US, the Joint Commission on Accreditation of Healthcare Organisations (JCAHO). Based on those recommendations, an ideal programme to prevent drug-food interactions would be a combined patient counselling and label system to select the most appropriate drug administration times and increase nurse and patient awareness of the potential for drug-food interactions. However, because of time constraints and limited resources, a label system or the provision of a drug-food interaction pamphlet to the patient before discharge would be a more practical method. Newsletters and educational in-services combined with patient counselling or a label system would be a valuable method to prevent drug-food interactions in hospitalised patients.

Becoming a "Greeble" expert: exploring mechanisms for face recognition.

Sensitivity to configural changes in face processing has been cited as evidence for face-exclusive mechanisms. Alternatively, general mechanisms could be fine-tuned by experience with homogeneous stimuli. We tested sensitivity to configural transformations for novices and experts with nonface stimuli ("Greebles"). Parts of transformed Greebles were identified via forced-choice recognition. Regardless of expertise level, the recognition of parts in the Studied configuration was better than in isolation, suggesting an object advantage. For experts, recognizing Greeble parts in a Transformed configuration was slower than in the Studied configuration, but only at upright. Thus, expertise with visually similar objects, not faces per se, may produce configural sensitivity.

Training 'greeble' experts: a framework for studying expert object recognition processes.

Twelve participants were trained to be experts at identifying a set of 'Greebles', novel objects that, like faces, all share a common spatial configuration. Tests comparing expert with novice performance revealed: (1) a surprising mix of generalizability and specificity in expert object recognition processes; and (2) that expertise is a multi-faceted phenomenon, neither adequately described by a single term nor adequately assessed by a single task. Greeble recognition by a simple neural-network model is also evaluated, and the model is found to account surprisingly well for both generalization and individuation using a single set of processes and representations.

Comparison of programs for preventing drug-nutrient interactions in hospitalized patients.

Three programs with different levels of pharmacist intervention designed to prevent drug-nutrient interactions (DNIs) were studied. Six drugs were selected for the study on the basis of their potential for involvement in significant DNIs and the hospital's drug-use profile. During a two-week control phase, the existing pharmacy system, in which no patient-specific information on DNIs is provided, was assessed. During the next four weeks, patients were randomly assigned to intervention 1, placement of a brightly colored label in the medication drawer and on the cover of the nursing medication card flip-chart, or to intervention 2, placement of the labels plus a five-minute structured patient-counseling session. Occurrence of DNIs and nurses' and patients' knowledge of DNIs were assessed. A DNI was defined as potentially altered drug absorption due to inappropriate timing or administration of a drug in relation to food. The occurrence of DNIs decreased significantly under the label system (from 24% to 19%) and under the combined label-counseling system (to 16%). However, the frequency of DNIs did not differ significantly between the two intervention groups. Patients' and nurses' knowledge of DNIs improved as a result of the interventions. The frequency of DNIs decreased when labels were used to alert nurses to proper medication timing.