Mechanistic constraints and the unlikely evolution of reciprocal cooperation.

Social evolution theory faces a puzzle: a gap between theoretical and empirical results on reciprocity. On the one hand, models show that reciprocity should evolve easily in a wide range of circumstances. On the other hand, empirically, few clear instances of reciprocity (even in a broad sense) have been found in nonhuman animals. In this paper, I aim to suggest and evaluate a novel reason concurring to solve this puzzle. I propose that it is difficult for reciprocity to evolve because it raises an evolutionary problem of bootstrapping: it requires that two complementary functions: (i) the ability to cooperate and (ii) the ability to respond conditionally to the cooperation of others, arise together and reach a significant frequency, whereas neither of them can be favoured in the absence of the other. I develop analytical models and simulations showing that, for this reason, the evolutionary emergence of reciprocal cooperation is highly unlikely. I then discuss the consequences of this result for our understanding of cooperation.

Cultural transmission and the evolution of human behaviour: a general approach based on the Price equation.

Transmitted culture can be viewed as an inheritance system somewhat independent of genes that is subject to processes of descent with modification in its own right. Although many authors have conceptualized cultural change as a Darwinian process, there is no generally agreed formal framework for defining key concepts such as natural selection, fitness, relatedness and altruism for the cultural case. Here, we present and explore such a framework using the Price equation. Assuming an isolated, independently measurable culturally transmitted trait, we show that cultural natural selection maximizes cultural fitness, a distinct quantity from genetic fitness, and also that cultural relatedness and cultural altruism are not reducible to or necessarily related to their genetic counterparts. We show that antagonistic coevolution will occur between genes and culture whenever cultural fitness is not perfectly aligned with genetic fitness, as genetic selection will shape psychological mechanisms to avoid susceptibility to cultural traits that bear a genetic fitness cost. We discuss the difficulties with conceptualizing cultural change using the framework of evolutionary theory, the degree to which cultural evolution is autonomous from genetic evolution, and the extent to which cultural change should be seen as a Darwinian process. We argue that the nonselection components of evolutionary change are much more important for culture than for genes, and that this and other important differences from the genetic case mean that different approaches and emphases are needed for cultural than genetic processes.

Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma.

Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.

Questioning the cultural evolution of altruism.

The evolutionary foundations of helping among nonkin in humans have been the object of intense debates in the past decades. One thesis has had a prominent influence in this debate: the suggestion that genuine altruism, strictly defined as a form of help that comes at a net fitness cost for the benefactor, might have evolved owing to cultural transmission. The gene-culture coevolution literature is wont to claim that cultural evolution changes the selective pressures that normally act to limit the emergence of altruistic behaviours. This paper aims to recall, however, that cultural transmission yields altruism only to the extent that it relies on maladaptive mechanisms, such as conformist imitation and (in some cases) payoff-biased transmission. This point is sometimes obscured in the literature by a confusion between genuine altruism, maladaptive by definition, and mutualistic forms of cooperation, that benefit all parties in the long run. Theories of cultural altruism do not lift the selective pressures weighing on strictly altruistic actions; they merely shift the burden of maladaptation from social cognition to cultural transmission.

Correction: Environmental adversity is associated with lower investment in collective actions.

[This corrects the article DOI: 10.1371/journal.pone.0236715.].

Environmental adversity is associated with lower investment in collective actions.

Environmental adversity is associated with a wide range of biological outcomes and behaviors that seem to fulfill a need to favor immediate over long-term benefits. Adversity is also associated with decreased investment in cooperation, which is defined as a long-term strategy. Beyond establishing the correlation between adversity and cooperation, the channel through which this relationship arises remains unclear. We propose that this relationship is mediated by a present bias at the psychological level, which is embodied in the reproduction-maintenance trade-off at the biological level. We report two pre-registered studies applying structural equation models to test this relationship on large-scale datasets (the European Values Study and the World Values Survey). The present study replicates existing research linking adverse environments (both in childhood and in adulthood) with decreased investment in adult cooperation and finds that this association is indeed mediated by variations in individuals' reproduction-maintenance trade-off.

Correction of Motion Artifacts Using a Multiscale Fully Convolutional Neural Network.

BACKGROUND AND PURPOSE: Motion artifacts are a frequent source of image degradation in the clinical application of MR imaging (MRI). Here we implement and validate an MRI motion-artifact correction method using a multiscale fully convolutional neural network. MATERIALS AND METHODS: The network was trained to identify motion artifacts in axial T2-weighted spin-echo images of the brain. Using an extensive data augmentation scheme and a motion artifact simulation pipeline, we created a synthetic training dataset of 93,600 images based on only 16 artifact-free clinical MRI cases. A blinded reader study using a unique test dataset of 28 additional clinical MRI cases with real patient motion was conducted to evaluate the performance of the network. RESULTS: Application of the network resulted in notably improved image quality without the loss of morphologic information. For synthetic test data, the average reduction in mean squared error was 41.84%. The blinded reader study on the real-world test data resulted in significant reduction in mean artifact scores across all cases (P < .03). CONCLUSIONS: Retrospective correction of motion artifacts using a multiscale fully convolutional network is promising and may mitigate the substantial motion-related problems in the clinical MRI workflow.

Spiral T1 Spin-Echo for Routine Postcontrast Brain MRI Exams: A Multicenter Multireader Clinical Evaluation.

BACKGROUND AND PURPOSE: Spiral MR imaging has several advantages compared with Cartesian MR imaging that can be leveraged for added clinical value. A multicenter multireader study was designed to compare spiral with standard-of-care Cartesian postcontrast structural brain MR imaging on the basis of relative performance in 10 metrics of image quality, artifact prevalence, and diagnostic benefit. MATERIALS AND METHODS: Seven clinical sites acquired 88 total subjects. For each subject, sites acquired 2 postcontrast MR imaging scans: a spiral 2D T1 spin-echo, and 1 of 4 routine Cartesian 2D T1 spin-echo/TSE scans (fully sampled spin-echo at 3T, 1.5T, partial Fourier, TSE). The spiral acquisition matched the Cartesian scan for scan time, geometry, and contrast. Nine neuroradiologists independently reviewed each subject, with the matching pair of spiral and Cartesian scans compared side-by-side, and scored on 10 image-quality metrics (5-point Likert scale) focused on intracranial assessment. The Wilcoxon signed rank test evaluated relative performance of spiral versus Cartesian, while the Kruskal-Wallis test assessed interprotocol differences. RESULTS: Spiral was superior to Cartesian in 7 of 10 metrics (flow artifact mitigation, SNR, GM/WM contrast, image sharpness, lesion conspicuity, preference for diagnosing abnormal enhancement, and overall intracranial image quality), comparable in 1 of 10 metrics (motion artifacts), and inferior in 2 of 10 metrics (susceptibility artifacts, overall extracranial image quality) related to magnetic susceptibility (P < .05). Interprotocol comparison confirmed relatively higher SNR and GM/WM contrast for partial Fourier and TSE protocol groups, respectively (P < .05). CONCLUSIONS: Spiral 2D T1 spin-echo for routine structural brain MR imaging is feasible in the clinic with conventional scanners and was preferred by neuroradiologists for overall postcontrast intracranial evaluation.

CT and appendicitis: evaluation of correlation between CT diagnosis and pathological diagnosis.

PURPOSE: To evaluate the correlation between appendiceal size measured by contrast-enhanced CT of the abdomen and pelvis and the size of surgically removed appendixes on gross pathological examination. MATERIALS AND METHODS: The initial database consisted of the cases of 301 children, collected over 2 years, of which 56 met inclusion criteria. Both the radiology and surgical pathology reports of these patients were reviewed. RESULTS: The mean size of appendixes meeting the CT size criteria of appendicitis was 10.3 mm, and that of the surgical pathology specimens was 10.4 mm. The pathological diagnosis of acute appendicitis was confirmed in 54 of 56 cases, yielding a positive predictive value of 96.4%. The Pearson product-moment correlation coefficient was calculated to be 0.5443 (95% CI 0.329 to 0.706). The slope of the linear correlation was 0.5788. The mean absolute difference in CT size versus pathological size was 2.2 mm. CONCLUSION: The data reveal a strong correlation in ability of CT to predict the presence of acute appendicitis, with moderate correlation in the size estimate of acutely inflamed appendixes, as imaged on CT, and the pathological specimen status after appendectomy.

Optimal Fat Suppression in Head and Neck MRI: Comparison of Multipoint Dixon with 2 Different Fat-Suppression Techniques, Spectral Presaturation and Inversion Recovery, and STIR.

BACKGROUND AND PURPOSE: Uniform complete fat suppression is essential for identification and characterization of most head and pathology. Our aim was to compare the multipoint Dixon turbo spin-echo fat-suppression technique with 2 different fat-suppression techniques, including a hybrid spectral presaturation with inversion recovery technique and an inversion recovery STIR technique, in head and neck fat-suppression MR imaging. MATERIALS AND METHODS: Head and neck MR imaging datasets of 72 consecutive patients were retrospectively reviewed. All patients were divided into 2 groups based on the type of fat-suppression techniques used (group A: STIR and spectral presaturation with inversion recovery gadolinium-T1WI; group B: multipoint Dixon T2 TSE and multipoint Dixon gadolinium-T1WI TSE). Objective and subjective image quality and scan acquisition times were assessed and compared between multipoint Dixon T2 TSE versus STIR and multipoint Dixon gadolinium-T1WI TSE versus spectral presaturation with inversion recovery gadolinium-T1WI using the Mann-Whitney U test. RESULTS: A total of 64 patients were enrolled in the study (group A, n = 33 and group B, n = 31). Signal intensity ratios were significantly higher for multipoint Dixon T2 and gadolinium-T1WI techniques compared with STIR (P < .001) and spectral presaturation with inversion recovery gadolinium-T1WI (P < .001), respectively. Two independent blinded readers revealed that multipoint Dixon T2 and gadolinium-T1WI techniques had significantly higher overall image quality (P = .022 and P < .001) and fat-suppression grades (P < .013 and P < .001 across 3 different regions) than STIR and spectral presaturation with inversion recovery gadolinium-T1WI, respectively. The scan acquisition time was relatively short for the multipoint Dixon technique (2 minutes versus 4 minutes 56 seconds for the T2-weighted sequence and 2 minutes versus 3 minutes for the gadolinium-T1WI sequence). CONCLUSIONS: The multipoint Dixon technique offers better image quality and uniform fat suppression at a shorter scan time compared with STIR and spectral presaturation with inversion recovery gadolinium-T1WI techniques.

Impact of model-based iterative reconstruction on image quality of contrast-enhanced neck CT.

BACKGROUND AND PURPOSE: Improved image quality is clinically desired for contrast-enhanced CT of the neck. We compared 30% adaptive statistical iterative reconstruction and model-based iterative reconstruction algorithms for the assessment of image quality of contrast-enhanced CT of the neck. MATERIALS AND METHODS: Neck contrast-enhanced CT data from 64 consecutive patients were reconstructed retrospectively by using 30% adaptive statistical iterative reconstruction and model-based iterative reconstruction. Objective image quality was assessed by comparing SNR, contrast-to-noise ratio, and background noise at levels 1 (mandible) and 2 (superior mediastinum). Two independent blinded readers subjectively graded the image quality on a scale of 1-5, (grade 5 = excellent image quality without artifacts and grade 1 = nondiagnostic image quality with significant artifacts). The percentage of agreement and disagreement between the 2 readers was assessed. RESULTS: Compared with 30% adaptive statistical iterative reconstruction, model-based iterative reconstruction significantly improved the SNR and contrast-to-noise ratio at levels 1 and 2. Model-based iterative reconstruction also decreased background noise at level 1 (P = .016), though there was no difference at level 2 (P = .61). Model-based iterative reconstruction was scored higher than 30% adaptive statistical iterative reconstruction by both reviewers at the nasopharynx (P < .001) and oropharynx (P < .001) and for overall image quality (P < .001) and was scored lower at the vocal cords (P < .001) and sternoclavicular junction (P < .001), due to artifacts related to thyroid shielding that were specific for model-based iterative reconstruction. CONCLUSIONS: Model-based iterative reconstruction offers improved subjective and objective image quality as evidenced by a higher SNR and contrast-to-noise ratio and lower background noise within the same dataset for contrast-enhanced neck CT. Model-based iterative reconstruction has the potential to reduce the radiation dose while maintaining the image quality, with a minor downside being prominent artifacts related to thyroid shield use on model-based iterative reconstruction.

Medial Occipital Lobe Hyperperfusion Identified by Arterial Spin-Labeling: A Poor Prognostic Sign in Patients with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy carries an uncertain prognosis. We sought to retrospectively assess the prognostic value of arterial spin-labeling MR imaging in 22 adult patients diagnosed with hypoxic-ischemic encephalopathy. Quantitative CBF maps were generated from the M0 map, and arterial spin-labeling data on a per-voxel basis were regionally interrogated via visual inspection and ROI placement. Hyperperfusion was defined as regional increases in CBF of >20% (relative to global CBF) and/or >100 mL/100 g/min. Eleven of 22 patients had prominent bilateral medial occipital lobe hyperperfusion, all of whom died before hospital discharge. One patient who had nondistinct arterial spin-labeling hyperperfusion and restricted diffusion survived. Medial occipital lobe hyperperfusion is a distinctive pattern that merits prospective investigation in a cohort of patients with moderate hypoxic-ischemic encephalopathy to determine its predictive ability in patients with a higher likelihood of survival.

Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke.

BACKGROUND AND PURPOSE: Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging. MATERIALS AND METHODS: Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information. RESULTS: Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts. CONCLUSIONS: Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

Improved T2* imaging without increase in scan time: SWI processing of 2D gradient echo.

BACKGROUND AND PURPOSE: 2D gradient-echo imaging is sensitive to T2* lesions (hemorrhages, mineralization, and vascular lesions), and susceptibility-weighted imaging is even more sensitive, but at the cost of additional scan time (SWI: 5-10 minutes; 2D gradient-echo: 2 minutes). The long acquisition time of SWI may pose challenges in motion-prone patients. We hypothesized that 2D SWI/phase unwrapped images processed from 2D gradient-echo imaging could improve T2* lesion detection. MATERIALS AND METHODS: 2D gradient-echo brain images of 50 consecutive pediatric patients (mean age, 8 years) acquired at 3T were retrospectively processed to generate 2D SWI/phase unwrapped images. The 2D gradient-echo and 2D SWI/phase unwrapped images were compared for various imaging parameters and were scored in a blinded fashion. RESULTS: Of 50 patients, 2D gradient-echo imaging detected T2* lesions in 29 patients and had normal findings in 21 patients. 2D SWI was more sensitive than standard 2D gradient-echo imaging in detecting T2* lesions (P < .0001). 2D SWI/phase unwrapped imaging also improved delineation of normal venous structures and nonpathologic calcifications and helped distinguish calcifications from hemorrhage. A few pitfalls of 2D SWI/phase unwrapped imaging were noted, including worsened motion and dental artifacts and challenges in detecting T2* lesions adjacent to calvaria or robust deoxygenated veins. CONCLUSIONS: 2D SWI and associated phase unwrapped images processed from standard 2D gradient-echo images were more sensitive in detecting T2* lesions and delineating normal venous structures and nonpathologic mineralization, and they also helped distinguish calcification at no additional scan time. SWI processing of 2D gradient-echo images may be a useful adjunct in cases in which longer scan times of 3D SWI are difficult to implement.

Identification of venous signal on arterial spin labeling improves diagnosis of dural arteriovenous fistulas and small arteriovenous malformations.

BACKGROUND AND PURPOSE: DAVFs and small AVMs are difficult to detect on conventional MR imaging/MRA or CTA examinations and often require DSA for definitive diagnosis. The purpose of this study was to assess the value of venous signal intensity on ASL imaging for making this diagnosis. MATERIALS AND METHODS: Two neuroradiologists and 1 neurologist reviewed MR imaging studies in 26 patients, 15 of whom had DSA-proved DAVFs or small (<2 cm) AVMs. Pseudocontinuous ASL was performed at 1.5T with background-suppressed 3D-FSE readout. Using a 5-point scale, these readers assessed the likelihood of positive findings on a DSA study before and after reviewing the ASL findings. Agreement on imaging findings, including venous ASL signal intensity, was performed by using κ statistics. Logistic regression and ROC analysis were performed to determine which imaging findings improved diagnosis. RESULTS: Venous ASL signal intensity was seen frequently in cases with positive findings on DSA. The sensitivity and specificity of venous ASL signal intensity for predicting positive findings on a DSA study were 78% and 85%, respectively. On ROC analysis, there was a significant increase in the AUC after review of the ASL images (AUC = 0.798 pre-ASL, AUC = 0.891 post-ASL; P = .02). Multivariate regression identified venous ASL signal intensity as the strongest predictor of positive findings on a DSA study, with an odds ratio of 17.3 (95% CI, 3.3-90.4). CONCLUSIONS: Identifying venous ASL signal intensity improved detection of DAVFs and small AVMs. Attention to this finding may improve triage to DSA in patients with suspected small vascular malformations.

Clinical evaluation of reduced field-of-view diffusion-weighted imaging of the cervical and thoracic spine and spinal cord.

BACKGROUND AND PURPOSE: DWI has the potential to improve the detection and evaluation of spine and spinal cord pathologies. This study assessed whether a recently described method (rFOV DWI) adds diagnostic value in clinical patients. MATERIALS AND METHODS: Consecutive patients undergoing clinically indicated cervical and/or thoracic spine imaging received standard anatomic sequences supplemented with sagittal rFOV DWI by using a b-value of 500 s/mm(2). Two neuroradiologists blinded to clinical history evaluated the standard anatomic sequences only for pathology and provided their level of confidence in their diagnosis. These readers then rescored the examinations after reviewing the rFOV DWI study and indicated whether this sequence altered findings or confidence levels. RESULTS: Two hundred twenty-three patients were included in this study. One hundred eighty patient scans (80.7%) demonstrated at least 1 pathologic finding. Interobserver agreement for identifying pathology (κ = 0.77) and in assessing the added value of the rFOV DWI sequence (κ = 0.77) was high. In pathologic cases, the rFOV DWI sequence added clinical utility in 33% of cases (P < .00001, Fisher exact test). The rFOV DWI sequence was found to be helpful in the evaluation of acute infarction, demyelination, infection, neoplasm, and intradural and epidural collections (P < .001, χ(2) test) and provided a significant increase in clinical confidence in the evaluation of 11 of the 15 pathologic subtypes assessed (P < .05, 1-sided paired Wilcoxon test). CONCLUSIONS: rFOV diffusion-weighted imaging of the cervical and thoracic spine is feasible in a clinical population and increases clinical confidence in the diagnosis of numerous common spinal pathologies.

Clinical assessment of standard and generalized autocalibrating partially parallel acquisition diffusion imaging: effects of reduction factor and spatial resolution.

BACKGROUND AND PURPOSE: PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique. MATERIALS AND METHODS: Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence. RESULTS: Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions. CONCLUSIONS: PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

Reduced field-of-view diffusion imaging of the human spinal cord: comparison with conventional single-shot echo-planar imaging.

BACKGROUND AND PURPOSE: DWI of the spinal cord is challenging because of its small size and artifacts associated with the most commonly used clinical imaging method, SS-EPI. We evaluated the performance of rFOV spinal cord DWI and compared it with the routine fFOV SS-EPI in a clinical population. MATERIALS AND METHODS: Thirty-six clinical patients underwent 1.5T MR imaging examination that included rFOV SS-EPI DWI of the cervical spinal cord as well as 2 comparison diffusion sequences: fFOV SS-EPI DWI normalized for either image readout time (low-resolution fFOV) or spatial resolution (high-resolution fFOV). ADC maps were created and compared between the methods by using single-factor analysis of variance. Two neuroradiologists blinded to sequence type rated the 3 DWI methods, based on susceptibility artifacts, perceived spatial resolution, signal intensity-to-noise ratio, anatomic detail, and clinical utility. RESULTS: ADC values for the rFOV and both fFOV sequences were not statistically different (rFOV: 1.01 ± 0.18 × 10(-3) mm(2)/s; low-resolution fFOV: 1.12 ± 0.22 × 10(-3) mm(2)/s; high-resolution fFOV: 1.10 ± 0.21 × 10(-3) mm(2)/s; F = 2.747, P > .05). The neuroradiologist reviewers rated the rFOV diffusion images superior in terms of all assessed measures (P < 0.0001). Particular improvements were noted in patients with metal hardware, degenerative disease, or both. CONCLUSIONS: rFOV DWI of the spinal cord overcomes many of the problems associated with conventional fFOV SS-EPI and is feasible in a clinical population. From a clinical standpoint, images were deemed superior to those created by using standard fFOV methods.

Peritumoral apparent diffusion coefficient as a metric of response in patients with recurrent glioblastoma multiforme treated with bevacizumab and irinotecan.

Bevacizumab and irinotecan have shown promising results in patients with recurrent glioblastoma multiforme (GBM), which traditionally carries a poor prognosis after first-line therapies have been exhausted. Retrospectively documenting the short-term effects of this chemotherapeutic regimen on recurrent GBM, as evidenced by comparative magnetic resonance images obtained two weeks prior to, and one-month following initiation of treatment, we hypothesize that peritumoral apparent diffusion coefficient (ADC) values will decrease on post-treatment scans. Brain MR data were collected from August 2005 to December 2006, in which post-contrast T1-weighted images demonstrated measurable enhancement or GBM tumor mass. Pre- and post-treatment MR images for ten consecutive patients were collected, each having failed temozolomide and radiation therapy. Pre- and post-treatment recurrent GBM bulk tumor and peritumoral T2 signal abnormality were measured in three dimensions. Diffusion of peritumoral T2 signal abnormality was evaluated on pre- and post-treatment ADC. All patients witnessed a significant decrease in tumor bulk ranging from 15.3% to 96.7% with a mean reduction of 48.2%, having received an average of two cycles of chemotherapy. FLAIR images demonstrated a mean volumetric reduction in peritumoral T2 signal abnormality of 44.3%. ADC measurements demonstrated an average reduction in peritumoral ADC of 20.6%, which was statistically significant (p-value < .005). Recurrent GBM tumor bulk demonstrated a 48.2% mean reduction, with corresponding decrease in peritumoral ADC values of 20.6%, suggesting that ADC may represent a valuable metric in the evaluation of the chemotherapeutic response of recurrent GBM, when treated with bevacizumab and irinotecan.

Relaying asymmetry of transient atropisomers of o-iodoanilides by radical cyclizations.

Atropisomers of N-2 degrees -alkyl-N-acryloyl-2-iodoanlides have been resolved by chromatography and crystallization-induced asymmetric transformation. These molecules have atropisomerization barriers of 23-24 kcal/mol and return to equilibrium ratios over several hours at ambient temperature in solution. The transient chirality can be locked in by radical cyclizations, which provide N-2 degrees -alkyl-3-methyl-1,3-dihydroindol-2-ones with high levels of chirality transfer. The mechanistic model features a stereoselective aryl radical cyclization that is more rapid than the rotation of the N-aryl bond of the anilide.