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.

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.

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.

Expertise training with novel objects leads to left-lateralized facelike electrophysiological responses.

Scalp event-related potentials (ERPs) in humans indicate that face and object processing differ approximately 170 ms following stimulus presentation, at the point of the N170 occipitotemporal component. The N170 is delayed and enhanced to inverted faces but not to inverted objects. We tested whether this inversion effect reflects early mechanisms exclusive to faces or whether it generalizes to other stimuli as a function of visual expertise. ERPs to upright and inverted faces and novel objects (Greebles) were recorded in 10 participants before and after 2 weeks of expertise training with Greebles. The N170 component was observed for both faces and Greebles. The results are consistent with previous reports in that the N170 was delayed and enhanced for inverted faces at recording sites in both hemispheres. For Greebles, the same effect of inversion was observed only for experts, primarily in the left hemisphere. These results suggest that the mechanisms underlying the electrophysiological face-inversion effect extend to visually homogeneous nonface object categories, at least in the left hemisphere, but only when such mechanisms are recruited by expertise.

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.

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.

The fusiform "face area" is part of a network that processes faces at the individual level.

According to modular models of cortical organization, many areas of the extrastriate cortex are dedicated to object categories. These models often assume an early processing stage for the detection of category membership. Can functional imaging isolate areas responsible for detection of members of a category, such as faces or letters? We consider whether responses in three different areas (two selective for faces and one selective for letters) support category detection. Activity in these areas habituates to the repeated presentation of one exemplar more than to the presentation of different exemplars of the same category, but only for the category for which the area is selective. Thus, these areas appear to play computational roles more complex than detection, processing stimuli at the individual level. Drawing from prior work, we suggest that face-selective areas may be involved in the perception of faces at the individual level, whereas letter-selective regions may be tuning themselves to font information in order to recognize letters more efficiently.

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.

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.

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.

Is face recognition not so unique after all?

In monkeys, a number of different neocortical as well as limbic structures have cell populations that respond preferentially to face stimuli. Face selectivity is also differentiated within itself: Cells in the inferior temporal and prefrontal cortex tend to respond to facial identity, others in the upper bank of the superior temporal sulcus to gaze directions, and yet another population in the amygdala to facial expression. The great majority of these cells are sensitive to the entire configuration of a face. Changing the spatial arrangement of the facial features greatly diminishes the neurons' response. It would appear, then, that an entire neural network for faces exists which contains units highly selective to complex configurations and that respond to different aspects of the object "face." Given the vital importance of face recognition in primates, this may not come as a surprise. But are faces the only objects represented in this way? Behavioural work in humans suggests that nonface objects may be processed like faces if subjects are required to discriminate between visually similar exemplars and acquire sufficient expertise in doing so. Recent neuroimaging studies in humans indicate that level of categorisation and expertise interact to produce the specialisation for faces in the middle fusiform gyrus. Here we discuss some new evidence in the monkey suggesting that any arbitrary homogeneous class of artificial objects-which the animal has to individually learn, remember, and recognise again and again from among a large number of distractors sharing a number of common features with the target-can induce configurational selectivity in the response of neurons in the visual system. For all of the animals tested, the neurons from which we recorded were located in the anterior inferotemporal cortex. However, as we have only recorded from the posterior and anterior ventrolateral temporal lobe, other cells with a similar selectivity for the same objects may also exist in areas of the medial temporal lobe or in the limbic structures of the same "expert" monkeys. It seems that the encoding scheme used for faces may also be employed for other classes with similar properties. Thus, regarding their neural encoding, faces are not "special" but rather the "default special" class in the primate recognition system.

Does visual subordinate-level categorisation engage the functionally defined fusiform face area?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level (e.g. bird) and subordinate-level (e.g. eagle) processing for both visual and semantic judgements. We localised the putative face area for 11 subjects, who also performed visual matching judgements for pictures and aurally presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgements, reflecting additional perceptual processing. When the face area was localised individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individuals face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face per se. Eight subjects also performed semantic judgements on aurally presented basic- and subordinate-level words. The parahippocampal gyri were more activated for subordinate-level than basic-level semantic judgements. Finally, the left posterior inferior temporal gyrus was activated for subordinate-level judgements, both visual and semantic, as well as during passive viewing of faces.

Can face recognition really be dissociated from object recognition?

We argue that the current literature on prosopagnosia fails to demonstrate unequivocal evidence for a disproportionate impairment for faces as compared to nonface objects. Two prosopagnosic subjects were tested for the discrimination of objects from several categories (face as well as nonface) at different levels of categorization (basic, subordinate, and exemplar levels). Several dependent measures were obtained including accuracy, signal detection measures, and response times. The results from Experiments 1 to 4 demonstrate that, in simultaneous-matching tasks, response times may reveal impairments with nonface objects in subjects whose error rates only indicate a face deficit. The results from Experiments 5 and 6 show that, given limited stimulus presentation times for face and nonface objects, the same subjects may demonstrate a deficit for both stimulus categories in sensitivity. In Experiments 7, 8 and 9, a match-to-sample task that places greater demands on memory led to comparable recognition sensitivity with both face and nonface objects. Regardless of object category, the prosopagnosic subjects were more affected by manipulations of the level of categorization than normal controls. This result raises questions regarding neuropsychological evidence for the modularity of face recognition, as well as its theoretical and methodological foundations.

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.