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Background and Purpose: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. Methods: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. Results: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26–115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack ( P 0 ( P P =0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. Conclusions: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02313909.

Rationale and Objectives To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. Materials and Methods Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. Results The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. Conclusions The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection.

Quantitative models of resurgence (e.g., Behavioral Momentum Theory, Resurgence as Choice) suggest that resurgence is partly a function of the duration of extinction exposure, with longer histories of extinction producing less resurgence. This prediction is supported by some laboratory research and has been partially supported by clinical translations that did not isolate the effects of extinction exposure prior to testing for resurgence. The degree to which different histories of extinction impact the likelihood of treatment relapse in therapeutic applications of differential reinforcement is of great interest to the clinical community, including insurance carriers and other financial providers. In the present study, we isolated the effects of extinction history for severe destructive behavior across six participants referred for treatment services and examined resurgence of destructive behavior when alternative reinforcement terminated. Our within-subject evaluation showed no difference in the level of resurgence or persistence of destructive behavior following short and long exposures to differential reinforcement with extinction. We discuss our failure to replicate in relation to experimental-design considerations for investigating this and other relapse phenomena in future research with clinical populations.

We compared the functions of problem behavior identified by (a) a functional analysis (FA), (b) an interview-informed synthesized contingency analysis (IISCA) that was informed by the results of an open-ended interview and a structured observation, and (c) a standardized-synthesized contingency analysis (SSCA) in which we synthesized three common functions of problem behavior across 12 individuals in a controlled consecutive case series. We then compared outcomes across assessments. The FA was sufficient in identifying the variables maintaining problem behavior for 11 of the 12 participants, replicating the findings of Fisher, Greer, Romani, Zangrillo, and Owen (2016). Error type (i.e., false positives, false negatives) and error prevalence were similar across functions identified by the IISCA and the SSCA, calling into question the utility of the open-ended interview and the structured observation that informed the IISCA.

Recent research suggests combining putative reinforcers for problem behavior into a single, synthesized contingency may increase efficiency in identifying behavioral function relative to traditional functional analysis (FA; Slaton, Hanley, & Raftery, 2017). Other research suggests potential shortcomings (e.g., false-positive outcomes; Fisher, Greer, Romani, Zangrillo, & Owen, 2016 ) of synthesized contingency analysis (SCA). In prior comparisons of traditional FAs and SCAs investigators could not ascertain with certainty the true function(s) of the participants’ problem behavior for use as the criterion variable. We conducted a translational study to circumvent this limitation by training a specific function for a surrogate destructive behavior prior to conducting a traditional FA and SCA. The traditional FA correctly identified the established function of the target response in all six cases and produced no iatrogenic effects. The SCA produced differentiated results in all cases and iatrogenic effects in three of six cases. We discuss these finding in terms the mechanisms that may promote iatrogenic effects.

Operant renewal is a form of relapse in which a previously extinguished response recurs due to a change in context. We designed two experiments to examine the impact of differential reinforcement of alternative behavior on ABA renewal in a translational model of relapse with 12 children. We compared levels of renewal in 2, 3-phase arrangements. In one arrangement, we reinforced target responding in Context A, extinguished responding in Context B, and returned to Context A while continuing to implement extinction. In a second arrangement, an alternative response produced reinforcement in Context B and during the return to Context A. Results across the two experiments indicated 3 general findings. First, extinction plus differential reinforcement disrupted target behavior more consistently in Context B relative to extinction alone. Second, renewal tended to be greater and more persistent during extinction alone relative to extinction plus differential reinforcement. Third, the renewal effect appeared to depend on whether the alternative response had a history of extinction in Context A. We discuss methodological implications for the treatment of severe destructive behavior.

Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) was developed to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging and provide guidelines for biopsy of multiparametric magnetic resonance imaging findings. We prospectively evaluated the cancer detection rate at each overall PI-RADSv2 score.This prospective study included 62 consecutive patients with 116 lesions who underwent multiparametric prostate magnetic resonance imaging at 3T with PI-RADSv2 evaluation and subsequent targeted magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and concurrent 12-core systematic prostate biopsy between May and September 2015. Median patient age and prostate specific antigen values were 65.5 years (range 50.3 to 76.6) and 7.10 ng/ml (range 0.47 to 863.0), respectively. Mean lesion size was 12.7 mm overall. Lesion based cancer detection rates for all tumors and for Gleason 3+4 or greater tumors at each PI-RADSv2 score were calculated. Univariate analysis was performed to assess differences in the cancer detection rate among PI-RADSv2 scores.A total of 116 lesions in 62 patients were evaluated prospectively (0 PI-RADS 1, 18 PI-RADS 2, 19 PI-RADS 3, 47 PI-RADS 4, 32 PI-RADS 5), and the patients underwent magnetic resonance/transrectal ultrasound fusion guided biopsy and systematic biopsy. Histopathology revealed 55 of 116 (47.4%) cancers (17 Gleason 3+3, 16 Gleason 3+4, 6 Gleason 4+3, 12 Gleason 4+4, 3 Gleason 4+5 and 1 Gleason 5+4). Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADS 2, 3, 4 and 5 scores for all tumors was 22.2%, 15.8%, 29.8% and 78.1%, respectively. The cancer detection rate of PI-RADS 2, 3, 4 and 5 scores for Gleason 3+4 or greater tumors was 5.6%, 0%, 21.3% and 75%, respectively. Differences in the cancer detection rate between overall PI-RADS 4 and 5 scores were significant (p0.001 for Gleason greater than 3+3 and Gleason 3+4 or greater cancers).A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.

Noncontingent reinforcement (NCR) and response blocking are 2 common interventions for problem behavior maintained by automatic reinforcement. We implemented NCR and blocking with 1 boy and found this combined intervention to be effective at decreasing high rates of automatically reinforced pica. With another child, we compared the effects of blocking alone to the combined intervention. With the 3rd child, we compared NCR alone and blocking alone to the combined intervention. Results showed that the combined intervention was effective at reducing automatically reinforced problem behavior while moderate to high levels of item engagement were maintained. When evaluated individually, neither NCR nor blocking was sufficient to reduce problem behavior to clinically significant levels.

In the clinic, differential reinforcement of alternative behavior (DRA) often involves programming extinction for destructive behavior while reinforcing an alternative form of communication (e.g., a functional communication response); however, implementing extinction can be unsafe or impractical under some circumstances. Quantitative theories of resurgence (i.e., Behavioral Momentum Theory and Resurgence as Choice) predict differences in the efficacy of treatments that do and do not involve extinction of target responding when reinforcement conditions maintaining alternative responding worsen. We tested these predictions by examining resurgence following two DRA conditions in which we equated rates of reinforcement. In DRA without extinction, target and alternative behavior produced reinforcement. In DRA with extinction plus noncontingent reinforcement, only alternative behavior produced reinforcement. We conducted this study in a reverse-translation sequence, first with participants who engaged in destructive behavior (Experiment 1) and then in a laboratory setting with rats (Experiment 2). Across both experiments, we observed proportionally lower levels of target responding during and following the DRA condition that arranged extinction for the target response. However, levels of resurgence were similar following both arrangements.

Concepts from behavioral momentum theory, along with some empirical findings, suggest that the rate of baseline reinforcement may contribute to the relapse of severe destructive behavior. With seven children who engaged in destructive behavior, we tested this hypothesis in the context of functional communication training by comparing the effects of different baseline reinforcement rates on resurgence during a treatment challenge (i.e., extinction). We observed convincing resurgence of destructive behavior in four of seven participants, and we observed more resurgence in the condition associated with high-rate baseline reinforcement (i.e., variable-interval 2 s in Experiment 1 or fixed-ratio 1 in Experiment 2) compared to a low-rate baseline reinforcement condition. We discuss the implications of these results relative to schedules of reinforcement in the treatment of destructive behavior and strategies to mitigate resurgence in clinical settings.

Background: \ud Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial.\ud \ud Methods: \ud NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy.\ud \ud Findings: \ud Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity.\ud \ud Interpretation: \ud Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted.\ud \ud Funding: \ud Bayer and Janssen.

OBJECTIVE. The purposes of this study were to assess correlation of apparent diffusion coefficient (ADC) and normalized ADC (ratio of tumor to nontumor tissue) with the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and updated International Society of Urological Pathology (ISUP) categories and to determine how to optimally use ADC metrics for objective assistance in categorizing lesions within PI-RADSv2 guidelines. MATERIALS AND METHODS. In this retrospective study, 100 patients (median age, 62 years; range, 44–75 years; prostate-specific antigen level, 7.18 ng/mL; range, 1.70–84.56 ng/mL) underwent 3-T multiparametric MRI of the prostate with an endorectal coil. Mean ADC was extracted from ROIs based on subsequent prostatectomy specimens. Histopathologic analysis revealed 172 lesions (113 peripheral, 59 transition zone). Two radiologists blinded to histopathologic outcome assigned PI-RADSv2 categories. Kendall tau was used to correlate ADC metrics with PI-RADSv2 and ISUP categories. ROC curves were used to assess the utility of ADC metrics in differentiating each reader’s PI-RADSv2 DWI category 4 or 5 assessment in the whole prostate and by zone. RESULTS. ADC metrics negatively correlated with ISUP category in the whole prostate (ADC, τ = −0.21, p = 0.0002; normalized ADC, τ = −0.21, p = 0.0001). Moderate negative correlation was found in expert PI-RADSv2 DWI categories (ADC, τ = −0.34; normalized ADC, τ = −0.31; each p < 0.0001) maintained across zones. In the whole prostate, AUCs of ADC and normalized ADC were 87% and 82% for predicting expert PI-RADSv2 DWI category 4 or 5. A derived optimal cutoff ADC less than 1061 and normalized ADC less than 0.65 achieved positive predictive values of 83% and 84% for correct classification of PI-RADSv2 DWI category 4 or 5 by an expert reader. Consistent relations and predictive values were found by an independent novice reader. CONCLUSION. ADC and normalized ADC inversely correlate with PI-RADSv2 and ISUP categories and can serve as quantitative metrics to assist with assigning PI-RADSv2 DWI category 4 or 5.

To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists. Nine radiologists (three each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone—peripheral (PZ) and transition (TZ). Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%; p = 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD improved agreement between all readers (56.9% vs 71.8%; p < 0.001). CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience. • Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. • CAD assistance improves agreement between radiologists in detecting prostate cancer lesions. • However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone. • CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence.

Purpose To characterize clinically important prostate cancers missed at multiparametric (MP) magnetic resonance (MR) imaging. Materials and Methods The local institutional review board approved this HIPAA-compliant retrospective single-center study, which included 100 consecutive patients who had undergone MP MR imaging and subsequent radical prostatectomy. A genitourinary pathologist blinded to MP MR findings outlined prostate cancers on whole-mount pathology slices. Two readers correlated mapped lesions with reports of prospectively read MP MR images. Readers were blinded to histopathology results during prospective reading. At histopathologic examination, 80 clinically unimportant lesions (5 mm; Gleason score, 3+3) were excluded. The same two readers, who were not blinded to histopathologic findings, retrospectively reviewed cancers missed at MP MR imaging and assigned a Prostate Imaging Reporting and Data System (PI-RADS) version 2 score to better understand false-negative lesion characteristics. Descriptive statistics were used to define patient characteristics, including age, prostate-specific antigen (PSA) level, PSA density, race, digital rectal examination results, and biopsy results before MR imaging. Student t test was used to determine any demographic differences between patients with false-negative MP MR imaging findings and those with correct prospective identification of all lesions. Results Of the 162 lesions, 136 (84%) were correctly identified with MP MR imaging. Size of eight lesions was underestimated. Among the 26 (16%) lesions missed at MP MR imaging, Gleason score was 3+4 in 17 (65%), 4+3 in one (4%), 4+4 in seven (27%), and 4+5 in one (4%). Retrospective PI-RADS version 2 scores were assigned (PI-RADS 1, n = 8; PI-RADS 2, n = 7; PI-RADS 3, n = 6; and PI-RADS 4, n = 5). On a per-patient basis, MP MR imaging depicted clinically important prostate cancer in 99 of 100 patients. At least one clinically important tumor was missed in 26 (26%) patients, and lesion size was underestimated in eight (8%). Conclusion Clinically important lesions can be missed or their size can be underestimated at MP MR imaging. Of missed lesions, 58% were not seen or were characterized as benign findings at second-look analysis. Recognition of the limitations of MP MR imaging is important, and new approaches to reduce this false-negative rate are needed.

Purpose To validate the dominant pulse sequence paradigm and limited role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the Prostate Imaging Reporting and Data System (PI-RADS) version 2 for prostate multiparametric MR imaging by using data from a multireader study. Materials and Methods This HIPAA-compliant retrospective interpretation of prospectively acquired data was approved by the local ethics committee. Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging. A total of 163 patients were evaluated, 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings. Nine radiologists participated in this study and interpreted images in 58 patients, on average (range, 56-60 patients). Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings. Probability of cancer detection for overall, T2-weighted, and diffusion-weighted (DW) imaging PI-RADS scores was calculated in the peripheral zone (PZ) and transition zone (TZ) by using generalized estimating equations. To determine dominant pulse sequence and benefit of dynamic contrast-enhanced (DCE) imaging, odds ratios (ORs) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression. Results A total of 654 lesions (420 in the PZ) were detected. The probability of cancer detection for PI-RADS category 2, 3, 4, and 5 lesions was 15.7%, 33.1%, 70.5%, and 90.7%, respectively. DW imaging outperformed T2-weighted imaging in the PZ (OR, 3.49 vs 2.45; P = .008). T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ (OR, 4.79 vs 3.77; P = .494). Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions (67.8% vs 40.0%, P = .02). The addition of DCE imaging to DW imaging in the PZ was beneficial (OR, 2.0; P = .027), with an increase in the probability of cancer detection of 15.7%, 16.0%, and 9.2% for PI-RADS category 2, 3, and 4 lesions, respectively. Conclusion DW imaging outperforms T2-weighted imaging in the PZ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria. The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection.

Functional communication training (FCT) is an established treatment for destructive behavior that missucceeds in about 37% of cases when the reinforcement schedule for the functional communication response (FCR) is thinned using multiples schedules (mult FCT; Hagopian, Boelter, & Jarmolowicz, 2011). In this investigation, we evaluated the use of response restriction FCT (RR FCT) in a cohort of patients with poorly differentiated responding of the FCR during mult FCT. Results showed that (a) RR FCT maintained high rates of correct FCRs during the reinforcement component of RR FCT without increasing destructive behavior; (b) children displayed highly discriminated FCRs when an FCR card and a control card were simultaneously available during the reinforcement component of RR FCT; and (c) near-zero rates of destructive behavior were observed during the last five sessions of the terminal reinforcement schedule. Results are discussed relative to differences between mult FCT and RR FCT and successive and simultaneous discriminations.

Background and aims Randomised controlled trials demonstrate that the anti-tumour necrosis factor-α (anti-TNFα) therapies infliximab and adalimumab are effective in inducing remission and preventing relapse of Crohn's disease (CD). As few studies have compared costs and efficacy of these two drugs directly, we examined this issue. Methods Data were collected for patients receiving either drug as first-line anti-TNFα for CD. Patients were matched as closely as possible on age, gender, weight, height, and date of commencement of therapy. Response to induction therapy was assessed at 12 weeks, and sustained clinical benefit at last point of follow-up. Resource data were collected for all patients until study end, with National Health Services reference costs applied to calculate the total cost per patient with adalimumab compared with infliximab. Results Thirty-six patients had been treated with adalimumab as first-line anti-TNFα since 2010. We matched an identical number of infliximab patients. Demographic data were similar between the two groups. Costs were significantly lower with adalimumab (£6692.95 less per patient (95% confidence interval £1816.61–£11569.29)), which was largely driven by the drug costs and drug administration costs associated with infliximab. Twenty-nine (80.6%) patients responded to induction therapy with both drugs, and 22 (61.1%) achieved glucocorticosteroid-free sustained clinical benefit with either drug at last point of follow-up. Conclusions Costs of infliximab used as first-line anti-TNFα therapy are greater, which may have implications for selection. Clinical outcomes appeared comparable, although power to detect a statistically significant difference would be limited.

Much criticism has been leveled at screening for prostate cancer using prostate-specific antigen (PSA) testing, yet there is no suitable replacement to improve the detection of clinically significant cancer (CSC). Prostate multiparametric magnetic resonance imaging (mpMRI) combined with mpMRI-guided biopsies is one possible solution, as it reduces detection of low-grade disease and increases detection of CSC. However, mpMRI is critically limited by lack of standardization across institutions and low interobserver agreement. The Prostate Imaging Reporting and Diagnostic System version 2 (PI-RADSv2) aims to address these concerns. We discuss the clinical and technical considerations for implementing PI-RADSv2, how we have adapted to PI-RADSv2, and review current research. While PI-RADSv2 represents a major step forward for standardizing prostate mpMRI, it does not provide a level of standardization that is routine with clinical blood tests and reader reproducibility remains an issue. Future research should seek to further improve quality assurance of mpMRI building on the important contributions of PI-RADSv2. Level of evidence 5 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:11-23.

Arranging periods in which requests for reinforcement are denied in a multiple schedule may result in increased destructive behavior during these periods for individuals who receive functional communication training (FCT) as treatment for severe destructive behavior. Providing access to competing activities during periods of reinforcer unavailability has been shown to minimize destructive behavior. We evaluated methods to identify effective competing activities for use when thinning reinforcement availability in a multiple schedule and compared competing activities embedded within the multiple schedule using an alternating-treatments design. Results suggested at least one competing activity facilitated favorable treatment outcomes for each participant. We discuss building on this empirical approach to identifying effective competing activities for use during reinforcement schedule thinning.

There is growing consensus that multiparametric magnetic resonance imaging (mpMRI) is an effective modality in the detection of locally recurrent prostate cancer after prostatectomy and radiation therapy. The emergence of magnetic resonance (MR)-guided focal therapies, such as cryoablation, high-intensity focused ultrasound, and laser ablation, have made the use of mpMRI even more important, as the normal anatomy is inevitably altered and the detection of recurrence is made more difficult. The aim of this article is to review the utility of mpMRI in detecting recurrent prostate cancer in patients following radical prostatectomy, radiation therapy, and focal therapy and to discuss expected post-treatment mpMRI findings, the varied appearance of recurrent tumors, and their mimics.

PURPOSE: Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. MATERIALS AND METHODS: Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. RESULTS: Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS ≥ 3 and 90% for PIRADS ≥ 4. Specialists performed better only for PIRADS ≥ 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. CONCLUSION: By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. LEVEL OF EVIDENCE: 1

Recent research findings (DeRosa, Fisher, & Steege, 2015) suggest that minimizing exposure to the establishing operation (EO) for destructive behavior when differential reinforcement interventions like functional communication training (FCT) are introduced may produce more immediate reductions in destructive behavior and prevent or mitigate extinction bursts. We directly tested this hypothesis by introducing FCT with extinction in two conditions, one with limited exposure to the EO (limited EO) and one with more extended exposure to the EO (extended EO) using a combined reversal and multielement design. Results showed that the limited-EO condition rapidly reduced destructive behavior to low levels during every application, whereas the extended-EO condition produced an extinction burst in five of six applications. We discuss these findings in relation to the effects of EO exposure on the beneficial and untoward effects of differential reinforcement interventions.

Background and Aims Non-response, loss of response, or intolerance to anti-tumour necrosis factor alpha (anti-TNFα) therapy is well recognised in Crohn's disease (CD) patients. Data concerning outcomes following the use of a second anti-TNFα therapy, particularly in patients who do not respond to a first anti-TNFα agent, are still emerging. The aim of this study was to assess response and tolerability to adalimumab following infliximab failure in a single centre cohort of CD patients. Methods Data were collected prospectively on 44 patients who received adalimumab therapy following infliximab failure. Initial response to adalimumab therapy at 6weeks following induction was defined using a two point decrease in the Harvey–Bradshaw Index, with remission at this point defined using a Harvey Bradshaw index≤4. Sustained clinical benefit at the last point of follow up was determined using a physician's global assessment. Corticosteroid-free sustained clinical benefit was also assessed at this point. Results Thirty-four (77%) patients had initial response to adalimumab therapy, with 28 (64%) having sustained clinical benefit. Corticosteroid-free sustained clinical benefit was achieved in nine (53%) of 17 patients requiring steroids at commencement of adalimumab. Four (44%) of the 9 patients who were primary non-responders to infliximab responded to adalimumab. The majority of CD patients who failed adalimumab therapy required surgery. Conclusions Second-line anti-TNFα therapy with adalimumab is effective at both inducing remission and maintaining response in CD patients who have failed infliximab, regardless of the reason for infliximab failure.

Background: Mycophenolate mofetil (MMF) is an immunomodulatory drug, and its use in inflammatory bowel disease has previously been reported. The aim of this study was to review the Leeds Colitis Clinic experience of the safety and efficacy of MMF in treating patients with refractory Crohn's disease (CD) and ulcerative colitis (UC). This is an extension of a previously published study from our center with a longer follow-up period and approximately twice the number of patients. Methods: A retrospective analysis was performed of the records of all patients treated with MMF for inflammatory bowel disease over a 5-year period. Results: Of 70 patients identified, 67 had previously been treated with azathioprine unsuccessfully. Seventeen of the 70 patients had been successfully maintained in remission with MMF for an average duration of 33 months. Treatment with MMF was discontinued for 53 patients, 17 because of side effects and 36 because they had not responded to the treatment. Conclusions: In our series, 17 patients (24.3%) had a sustained steroid-free remission with MMF therapy. Nineteen patients (27%) experienced side effects, of which 17 (24.3% of the total group) had to discontinue therapy. An additional 36 (51.4%) required an escalation in medical therapy or surgery because of failure of the MMF therapy. MMF may have a role in the treatment of refractory inflammatory bowel disease, especially in patients who have previously failed standard therapies such as azathioprine. (Inflamm Bowel Dis 2007)

Researchers typically modify individual functional analysis (FA) conditions after results are inconclusive (Hanley, Iwata,McCord, 2003). Hanley, Jin, Vanselow, and Hanratty (2014) introduced a marked departure from this practice, using an interview-informed synthesized contingency analysis (IISCA). In the test condition, they delivered multiple contingencies simultaneously (e.g., attention and escape) after each occurrence of problem behavior; in the control condition, they delivered those same reinforcers noncontingently and continuously. In the current investigation, we compared the results of the IISCA with a more traditional FA in which we evaluated each putative reinforcer individually. Four of 5 participants displayed destructive behavior that was sensitive to the individual contingencies evaluated in the traditional FA. By contrast, none of the participants showed a response pattern consistent with the assumption of the IISCA. We discuss the implications of these findings on the development of accurate and efficient functional analyses.

OBJECTIVE. The purpose of the present study is to determine whether abstinence from ejaculation before undergoing multiparametric prostate MRI increases seminal vesicle (SV) volume and therefore improves diagnostic interpretation of the SVs. MATERIALS AND METHODS. This retrospective study included 238 patients who underwent 3-T MRI of the prostate over a 4-month period. Patients were requested to complete a questionnaire that asked how long it had been since their last ejaculation (i.e., < 3 days vs ≥ 3 days). Forty-two patients (mean patient age, 62.0 years) indicated that it had been less than 3 days since their last ejaculation and were designated as group 1, whereas the remainder indicated an interval of 3 days or more since their last ejaculation. A group of 42 age-matched subjects (mean patient age, 62.1 years) were randomly selected from the remaining 196 patients and were designated as group 2. SV volumes were measured manually. Two radiologists who were blinded to group assignment and patient characteristics scored the right and left SVs separately to determine diagnostic interpretability, which was scored on a 3-point scale as follows: a score of 1 denoted that the SVs were not dilated and the score was nondiagnostic, a score of 2 indicated that the SVs were not dilated but the score was diagnostic, and a score of 3 denoted that the SVs were dilated and the score was diagnostic. Volume differences and interpretability scores were analyzed using a t test. Interobserver agreement was analyzed using the Cohen kappa statistic. A separate analysis was performed to evaluate differences in diagnostic interpretability for patients 60 years and younger versus patients older than 60 years, by use of the chi-square test and relative risk ratio analysis. RESULTS. The right, left, and total SV volumes for group 1 were 3.1 mL, 2.9 mL, and 6.0 mL, respectively, whereas those for group 2 were 4.7 mL, 4.1 mL, and 8.8 mL, respectively (p = 0.011). The mean interpretability scores for group 1 and group 2 were 2.0 and 2.5, respectively. For group 1, reader 1 and reader 2 assigned a nondiagnostic score for 10 and 13 patients, respectively, whereas for group 2, they assigned a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.03, for reader 2). For men in group 1 who were older than 60 years, reader 1 and reader 2 gave a nondiagnostic score for nine and 11 patients, respectively; whereas for men in group 2 who were older than 60 years, the readers gave a nondiagnostic score for two and five patients, respectively (p = 0.01, for reader 1; and p = 0.05, for reader 2). CONCLUSION. For men older than 60 years, abstinence from ejaculation for 3 or more days before undergoing MRI examination resulted in larger SV volumes and lower rates of nondiagnostic evaluation and therefore might improve evaluation of SV invasion on multiparametric MRI. The difference is less striking in men 60 years and younger.

Two principal goals of functional communication training (FCT) are (a) to eliminate destructive behavior and (b) to establish a more acceptable, yet functionally equivalent, communication response (FCR). A related and critically important goal is to thin the schedule of reinforcement for the FCR to levels that can be reasonably managed by caregivers. Researchers have described several approaches to thinning FCT reinforcement schedules. We summarize the results of 25 consecutive applications (among 20 cases) in which schedule-thinning procedures employed discriminative stimuli to signal when the FCR would and would not produce reinforcement (i.e., using multiple schedules, response restriction, or chained schedules). Results suggest that schedule-thinning procedures that use discriminative stimuli can maintain the effectiveness of FCT while they minimize the need for punishment or other supplemental procedures.

We evaluated the combined and sequential effects of 3 toilet-training procedures recommended for use with young children: (a) underwear, (b) a dense sit schedule, and (c) differential reinforcement. A total of 20 children participated. Classroom teachers implemented a toilet-training package consisting of all 3 procedures with 6 children. Of the 6 children, 2 showed clear and immediate improvements in toileting performance, and 3 showed delayed improvements. Teachers implemented components of the training package sequentially with 12 children. At least 2 of the 4 children who experienced the underwear component after baseline improved. Toileting performance did not improve for any of the 8 children who were initially exposed to either the dense sit schedule or differential reinforcement. When initial training components were ineffective, teachers implemented additional components sequentially until toileting performance improved or all components were implemented. Toileting performance often improved when underwear or differential reinforcement was later added.

Multiple schedules with signaled periods of reinforcement and extinction have been used to thin reinforcement schedules during functional communication training (FCT) to make the intervention more practical for parents and teachers. We evaluated whether these signals would also facilitate rapid transfer of treatment effects from one setting to the next and from one therapist to the next. With two children, we conducted FCT in the context of mixed (baseline) and multiple (treatment) schedules introduced across settings or therapists using a multiple baseline design. Results indicated that when the multiple schedules were introduced, the functional communication response came under rapid discriminative control, and problem behavior remained at near-zero rates. We extended these findings with another individual by using a more traditional baseline in which problem behavior produced reinforcement. Results replicated those of the previous participants and showed rapid reductions in problem behavior when multiple schedules were implemented across settings.

We conducted functional analyses (FA) with 4 typically developing preschool children during ongoing classroom activities and evaluated treatments that were based on FA results. Results of each child's FA suggested social-positive reinforcement functions, and differential reinforcement of alternative behavior plus time-out was effective in decreasing problem behavior and increasing appropriate behavior. We discuss the utility of classroom-based FAs and potential compromises to experimental control.

Background Infliximab is licenced for use in Crohn's disease (CD). Trial data demonstrate that infliximab is effective for inducing remission of active CD, healing fistulising CD, and preventing relapse once in remission. However, long-term data regarding efficacy, safety, and predictors of response are still emerging. Aim To examine these issues in a large cohort of patients who received infliximab for CD. Methods A retrospective analysis of prospectively collected data was performed for 210 patients receiving infliximab for luminal or fistulising CD. Response to infliximab induction therapy, and sustained clinical benefit, were assessed by a decrease in Harvey–Bradshaw Index (HBI) of ≥2 points. Remission was defined as an HBI ≤ 4. Physician's global assessment was used where HBI could not be obtained. Demographic and disease factors that may predict response to therapy were analysed by Kaplan–Meier plots and univariate and multivariate analyses. Results Overall, 173 (82.4%) patients responded to infliximab induction, with 114 (65.9%) achieving sustained clinical benefit. Almost 40% of the study cohort had an HBI ≤ 4, indicating remission, at last point of follow-up (median 24 months). Concomitant immunosuppression predicted sustained clinical benefit in the first 6 months of therapy (P = 0.03). An inflammatory disease phenotype (P = 0.04 univariate analysis, P = 0.03 Kaplan Meier analysis) and male gender (P = 0.03) also predicted sustained clinical benefit. Episodic therapy was associated with an increased likelihood of secondary non-response. Adverse events, including malignancies, were few. Conclusion In this single centre study, infliximab was efficacious and well-tolerated in CD.

Infliximab is effective for induction and maintenance of remission in patients with Crohn's disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease.To assess Crohn's disease-related costs of care and resource use in a single-centre cohort of patients with Crohn's disease 12 months pre- and post-infliximab therapy.Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease-related resource use was collected 12 months pre- and post-infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease-related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis.Cost savings were demonstrated in all areas of Crohn's disease-related resource use following infliximab therapy. Mean total Crohn's disease-related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post-infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased.Infliximab use resulted in Crohn's disease-related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.

This paper presents the development and implementation of an intra-operative magnetic resonance imaging (ioMRI) program using a moveable 3.0 T magnet with a large working aperture.A previously established prototype 1.5 T ioMRI program based on a ceiling-mounted moveable magnet was upgraded to 3.0 T. The upgrade included a short, 1.73 m, magnet with a large 70 cm working aperture (IMRIS, Winnipeg, Canada), whole-room radio-frequency shielding, and a fully functional MR-compatible operating room (OR) table. Between January and September 2009, 100 consecutive patients were evaluated at 3.0 T.The ioMRI upgrade maintained a patient-focused environment. When not needed for surgery, the magnet was moved to an adjacent room. A large aperture and streamlined OR table allowed freedom of patient positioning while maintaining access and visibility. Working at 3.0 T enabled application of advanced imaging sequences to the full spectrum of neurosurgical pathology in the ioMRI environment. The use of ioMRI continues to show unsuspected residual tumor in up to 20% of cases. There were no adverse events or technical system failures.An ioMRI program based a 3.0 T moveable magnet is feasible. By moving the magnet, the system maintains a patient-focused surgical environment and the ability to share the technology between medical disciplines.

Robotic systems are being introduced into surgery to extend human ability. NeuroArm represents a potential change in the way surgery is performed; this is the first image-guided, MR-compatible surgical robot capable of both microsurgery and stereotaxy. This paper presents the first surgical application of neuroArm in an investigation of microsurgical performance, navigation accuracy, and Phase I clinical studies. To evaluate microsurgical performance, 2 surgeons performed microsurgery (splenectomy, bilateral nephrectomy, and thymectomy) in a rodent model using neuroArm and conventional techniques. Two senior residents served as controls, using the conventional technique only (8 rats were used in each of the 3 treatment groups; the 2 surgeons each treated 4 rats from each group). Total surgery time, blood loss, thermal injury, vascular injury, and animal death due to surgical error were recorded and converted to an overall performance score. All values are reported as the mean +/- SEM when normally distributed and as the median and interquartile range when not. Surgeons were slower using neuroArm (1047 +/- 69 seconds) than with conventional microsurgical techniques (814 +/- 54 seconds; p = 0.019), but overall performance was equal (neuroArm: 1110 +/- 82 seconds; microsurgery: 1075 +/- 136 seconds; p = 0.825). Using microsurgery, the surgeons had overall performance scores equal to those of the control resident surgeons (p = 0.141). To evaluate navigation accuracy, the localization error of neuroArm was compared with an established system. Nanoparticles were implanted at predetermined bilateral targets in a cadaveric model (4 specimens) using image guidance. The mean localization error of neuroArm (4.35 +/- 1.68 mm) proved equal to that of the conventional navigation system (10.4 +/- 2.79 mm; p = 0.104). Using the conventional system, the surgeon was forced to retract the biopsy tool to correct the angle of entry in 2 of 4 trials. To evaluate Phase I clinical integration, the role of neuroArm was progressively increased in 5 neurosurgical procedures. The impacts of neuroArm on operating room (OR) staff, hardware, software, and registration system performance were evaluated. NeuroArm was well received by OR staff and progressively integrated into patient cases, starting with draping in Case 1. In Case 2 and all subsequent cases, the robot was registered. It was used for tumor resection in Cases 3-5. Three incidents involving restrictive cable length, constrictive draping, and reregistration failure were resolved. In Case 5, the neuroArm safety system successfully mitigated a hardware failure. NeuroArm performs as well and as accurately as conventional techniques, with demonstrated safety technology. Clinical integration was well received by OR staff, and successful tumor resection validates the surgical applicability of neuroArm.

Two studies demonstrated a functional relationship between a peer modeling procedure and the treatment of feeding disorders with 2 young children. In the first experiment, the use of a peer model treatment package was shown to induce swallowing in a child with dysphagia who had never swallowed food or liquid. In the second experiment, a child who consistently declined food was induced to increase food acceptance as a function of the same peer modeling package. In the latter experiment, a peer-mediated procedure, consisting of rotated opportunities to consume food with a peer, was found to increase consumption more than did modeling alone. The first experiment used a multiple baseline design across solids and liquids, and the second used a multiple treatment design. The results of both experiments are discussed as new and nonaversive treatments for feeding disorders of young children who are imitative.

Two experiments were conducted to study the effects of six processing techniques for barley grain in a 3 x 2 factorial arrangement of grain conditions and roller settings on ruminal degradation of the grain (Exp. 1) and on growth performance by 138 feedlot steers (n = 23 per treatment; Exp. 2). Dry barley (11% moisture, D barley), barley tempered to 20% moisture (M barley), and barley tempered with 60 mL/t of surfactant-based tempering agent (GrainPrep, Agrichem, Inc., Anoka, MN; MS barley), were each rolled at two roller settings selected from preliminary tests. The settings selected for the study were RD, the roller position that had yielded optimally processed D barley, and RMS, the setting that had yielded optimally processed MS barley. Setting RMS was tighter than RD. Barley rolled at the RMS setting was more extensively processed (i.e., had a lower [P0.001] processing index, PI), had lighter (P0.001) volume weight, thinner (P0.001) kernels, and fewer (P0.001) whole kernels compared with setting RD. Tempering did not affect (P0.05) PI, percentage of whole kernels, or kernel thickness at either roller setting. The processing characteristics of tempered barley were unaffected (P0.05) by surfactant. The extent of in situ DM disappearance (ISDMD) was higher (P0.01) in grain rolled at setting RMS compared with RD. At both roller settings, tempering reduced (P0.05) ISDMD between 4 and 24 h of ruminal incubation. Steers fed RMS-rolled barley had lower (P0.001) DMI, slightly lower (P = 0.084) ADG, but increased (P0.05) gain:feed (G:F) compared with steers fed RD-rolled barley. Tempering did not affect (P0.05) ADG, DMI, or G:F during backgrounding, but improved (P0.01) these variables during finishing. Surfactant improved (P0.05) G:F but not DMI or ADG. The improvement in G:F was most pronounced when setting RMS was used. The optimal PI values calculated from performance data were numerically greater for the backgrounding diet than for the finishing diet. Steers fed M or MS barley had heavier (P0.01) hot carcasses and thicker (P0.05) fat cover but lower (P0.05) dressing percentages than steers fed D. When the feed barley was rolled at setting RMS, steers fed MS barley produced heavier (P0.05) carcasses than those fed M. Tempering with or without surfactant increased performance by feedlot steers compared with not tempering. Diet composition and degree of barley processing mediated this effect.

To suggest infliximab (IFX) is effective for acute severe ulcerative colitis, from real-life clinical practice.All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included. Data were extracted from clinical records in order to assess response to IFX therapy. The primary endpoint was colectomy-free survival, and secondary outcomes included glucocorticosteroid-free remission and safety, which was evaluated by recording deaths and adverse events. Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free, both at discharge from their index admission, and during follow-up after an initial response to IFX were compared.Forty-four patients (16 females, mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis. The median duration of follow-up post-first infusion was 396 d (interquartile range = 173-828 d). There were 21 (47.7%) patients with1 year of follow-up, 10 (22.7%) with 1 years to 2 years of follow-up, and 13 (29.5%) with2 years of follow-up post-first infusion of IFX. Overall, 35 (79.5%) responded to IFX, avoiding colectomy during their index admission, 29 (65.9%) were colectomy-free at last point of follow-up (median follow-up 396 d), and 25 (56.8%) were in glucocorticosteroid-free remission at end of follow-up. There was one death from post-operative sepsis, 20 d after a single IFX infusion. Colectomy rates were generally lower among those "bridging" to thiopurine. Of 18 patients "bridged" to thiopurine therapy, 17 (94.4%) were colectomy-free, and 15 (83.3%) were in glucocorticosteroid-free remission at study end. No predictors of response were identified.IFX is effective for acute severe ulcerative colitis in real-life clinical practice. Two-thirds of patients avoided colectomy, and more than 50% were in glucocorticosteroid-free remission.

Operant procedures were tested on three patients who had been in vegetative coma for 6 months, 10 months, and 38 months. A discrete trial procedure was used to test compliance to verbal requests for three behaviors for each patient, including lateral head movement or finger movement, eye focus or eye squeeze, and mouth movement. The design for each patient consisted of multiple baselines across three behaviors with a withdrawal phase and a reinstatement phase (ABAB) for one behavior. Baseline phases were followed by contingent music phases in which 15-second taped excerpts of patients' preferred music sounded immediately following the emission of targeted behaviors. The contingent music treatment affected all three behaviors for Patient 1, but was less effective for two out of three behaviors for the second and third patients who had been in coma for more extensive periods of time. Results are discussed in terms of the potential contributions of the use of operant assessment and treatment procedures in an area of medicine where they have not been used before.

The maturation of Sertoli cell function was studied by observing properties of cells obtained from 15-, 25-, and 35-day-old rats after 3 days in culture gamma-Glutamyl transpeptidase activity, expressed per mg DNA or per mg protein, and total and soluble protein to DNA ratios increased with age. In contrast, lactate dehydrogenase activity was unchanged between 15 and 35 days of age. Secreted protein to DNA ratios and the secretion of lactate, androgen-binding protein (ABP), and transferrin per mg DNA also increased with age. Two-dimensional electrophoresis maps of [35S]methionine-labeled secretory proteins indicated the appearance of two specific bands [mol wt, 66,000; pI 6.0-6.8 (band 1); mol wt, 56,000; pI 5.3-6.0 (band 2)] between 15 and 35 days of age. The hormone dependence of these parameters was studied in Sertoli cells isolated from rats hypophysectomized at 20 days of age and subsequently treated with oil, testosterone propionate, or testosterone propionate plus FSH for 15-21 days. Hypophysectomy decreased total, soluble, and secreted protein to DNA ratios; hormone treatment in vivo increased these ratios compared to oil treatment. gamma-Glutamyl transpeptidase activity was significantly decreased by hypophysectomy and increased, compared to oil treatment, by hormone treatment. In contrast, lactate dehydrogenase activity per mg DNA was also decreased by hypophysectomy, but was unaffected by hormone treatment. [35S]Methionine incorporation into secreted protein and secretion of ABP and lactate per mg DNA were all decreased by hypophysectomy, whereas transferrin secretion per mg DNA was unaffected. While the hormone treatments increased ABP secretion, they had no effect on lactate or transferrin secretion, expressed per mg DNA. The [35S]methionine-labeled secretory proteins (bands 1 and 2) were not visible in two-dimensional electrophoresis maps after hypophysectomy of the donor animals. Treatment with testosterone propionate or testosterone propionate plus FSH in vivo resulted in the appearance of the acidic components of band 2. These data demonstrate that changes reflecting in vivo maturational patterns and hormonal influences on Sertoli cell function persist, at least in a relative sense, after 3 days in culture. Although the majority of [35S]methionine-labeled Sertoli cell cellular and secretory proteins were present under all conditions, maturation- and hormone-dependent changes in a number of specific functions were demonstrated.

SUMMARY A study of 65 patients with acute onset of a focal neurological disorder in infancy and childhood revealed that 42 had fever or seizures or both at the time of onset of the neurologic disability and that 23 had neither fever nor seizures. The group with fever or seizures or both had an earlier age of onset, an increased incidence of preceding infection, more widespread and more severe physical findings, and a poorer prognosis with greater residual disability. Although inconclusive, evidence indicates that the neurologic deficit in many children with fever or seizures or both may be due to a focal inflammatory process and in many without fever or seizures to an ischemic process. RESUME Desordres neurologiques aigus de l'enfance Une etude de 65 patients avec un commencement aigu de desordre neurologique focal pendant la premiere et la grande enfance a revele que 42 avaient de la fievre ou des crises ou bien les deux a la fois au moment du debut de l'invalidite neurologique et que 25 n'avaient ni fievre ni crises. Le groupe avec fievre ou crises ou les deux a la fois avait un plus jeune âge au moment de l'apparition de la maladie qui etait plus souvent precedee par une infection, comportait des symptomes plus etendus et severes, et dont le prognostic etait plus grave avec une plus grande invalidite residuelle. Sans pouvoir conclure definitivement, on peut dire que le deficit neurologique chez de nombreux enfants avec fievre ou crises ou les deux a la fois pourrait etre dua un processus inflammatoire focal, et chez de nombreux enfants sans fievre ou crises a un processus ischemique. ZUSAMMENFASSUNG Akute neurologische Storungen im Sauglings und Kindesalter Eine Studie von 65 Patienten mit akuten Erscheinungen einer fokalen neurologischen Storung im Sauglings- und Kindesalter ergab dass 42 Fieber oder Anfalle oder beides zur Zeit des Beginns der neurologischen Storung, und dass 23 weder Fieber nqch Anfalle hatten. Die Gruppe mit Fieber oder Anfallen oder beidem waren friiher betroffen worden, wiesen ein haufigeres Vorkommen vorhergegangener Infektion auf, weiter verbreitete und ernsthaftere physische Befunde und eine schwachere Prognose mit grosseren bleibenden Schaden. Obwohl das Beweismaterial nicht schliissig ist, weist es doch darauf hin dass das neurologische Defizit bei vielen Kindern, die Fieber oder Anfalle oder beides hatten, von einem fokalen Inflammations-Prozess herriihren kann, und bei vielen der nicht mit Fieber oder Anfallen Erkrankten von einem isochemischen Prozess stammen kann. RESUMEN Disturbios neurologicos agudos en la infancia y la ninez Se han estudiado 65 pacientes que tuvieron un acceso agudo de un disturbio neurologico focal durante la infancia o la ninez. Se hallo que 42 ya padecian de fiebre o de ataques o de ambos cuando empezo la incapacidad neurologica, y que 23 no padecian ni de fiebre ni de ataques. En el grupo con fiebre o ataques o ambos, la enfermedad neurologica empezo cuando eran mas jovenes; habia una incidencia mayor de infecciones anteriores, incapaci-dades fisicas mas extensas y mas graves, y un pronostico peor con mayores incapacidades residuas. Aunque no decisiva, la evidencia da que pensar que el defecit neurologico en muchos nifios que padecen de fiebre o de ataques o de ambos puede resultar de una actividad inflamatoria focal, y en muchos que no tienen fiebre ni ataques de una actividad isquemica.

Excerpt Five patients with fatal encephalitis have come under our observation in a 2-year period. Herpes simplex virus was isolated from the brain in all of these cases. The neurologic picture coul...