Subacute cutaneous lupus erythematosus and dermatomyositis associated with anti-programmed cell death 1 therapy.

Programmed cell death 1 (PD-1) blockade has rapidly emerged as an effective therapy for a wide variety of metastatic malignancies. It has been associated with multiple immune-related adverse effects, including cutaneous eruptions. We describe two patients with clinical and histological findings that were consistent with subacute cutaneous lupus erythematosus (SCLE) after receiving PD-1 inhibitor therapy for metastatic lung cancer. We successfully treated our first patient with systemic and topical steroids, photoprotection and hydroxychloroquine. However, he subsequently developed dermatomyositis after continuing PD-1 inhibitor therapy. Our second patient presented with a protracted course of a cutaneous eruption in spite of discontinuation of anti-PD-1 therapy and treatment with systemic corticosteroids and infliximab. This patient's SCLE resolved after the addition of topical steroids and photoprotection and discontinuation of anti-tumour necrosis factor therapy. She and her oncology team decided to pursue non-PD-1 inhibitor treatment for lung cancer owing to a lack of tumour response. We add SCLE and dermatomyositis to the growing list of autoimmune complications of PD-1 blockade. Our cases raise a number of questions, particularly in relation to the viability of continuing anti-PD-1 therapy after developing SCLE and the role of immunosuppressive therapy in patients with PD-1 inhibitor-associated connective tissue disease. What's already known about this topic? Programmed cell death 1 (PD-1) blockade, which is rapidly emerging as a therapy for a wide variety of metastatic malignancies, has been associated with multiple immune-related adverse effects. These include systemic autoimmune diseases such as colitis and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects of PD-1 inhibitors most commonly reported in clinical trials include lichenoid reactions, eczematous dermatitis and vitiligo. What does this study add? We report two cases of PD-1 inhibitor-associated subacute cutaneous lupus erythematosus (SCLE), with one patient progressing to dermatomyositis with continued PD-1 inhibitor treatment. In addition to being a novel cutaneous adverse event, we also demonstrate the possibility of development of multiple autoimmune diseases in one patient, which is different from classic drug-related SCLE. We discuss the treatment challenges for patients with autoimmune skin disease receiving PD-1 inhibitor therapy.

Pilot feasibility study examining a structured self-management diabetes education programme, DESMOND-ID, targeting HbA1c in adults with intellectual disabilities.

AIM: To report on the outcomes of a pilot feasibility study of a structured self-management diabetes education programme targeting HbA1c . METHODS: We conducted a two-arm, individually randomized, pilot superiority trial for adults with intellectual disability and Type 2 diabetes mellitus. A total of 66 adults with disabilities across the UK met the eligibility criteria. Of these, 39 agreed to participate and were randomly assigned to either the DESMOND-ID programme (n = 19) or a control group (n = 20). The programme consisted of seven weekly educational sessions. The primary outcome was HbA1c level, and secondary outcomes included BMI, diabetes illness perceptions, severity of diabetes, quality of life, and attendance rates. RESULTS: This study found that the DESMOND-ID programme was feasible to deliver. With reasonable adjustments, the participants could be recruited successfully, and could provide consent, complete the outcome measures, be randomized to the groups and attend most of the sessions, with minimal loss to follow-up. The fixed-effects model, the interaction between occasion (time) and condition, showed statistically significant results (0.05 level) for HbA1c ; however, the CI was large. CONCLUSION: This is the first published study to adapt and pilot a national structured self-management diabetes education programme for adults with intellectual disability. This study shows it is possible to identify, recruit, consent and randomize adults with intellectual disabilities to an intervention or control group. Internationally, the results of this pilot are promising, demonstrating that a multi-session education programme is acceptable and feasible to deliver. Its effectiveness should be further tested in an adequately powered trial.

Novel therapies for the treatment of advanced prostate cancer.

In recent years, great success has been achieved on many fronts in the treatment of men with metastatic castration-resistant prostate cancer (CRPC), including novel chemotherapeutics, immunotherapies, bone microenvironment-targeted agents, and hormonal therapies. Numerous agents are currently in early-phase clinical trial development for the treatment of advanced prostate cancer. These novel therapies target several areas of prostate tumor biology, including the upregulation of androgen signaling and biosynthesis, critical oncogenic intracellular pathways, epigenetic alterations, and cancer immunology. Importantly, the characterization of the prostate cancer genome offers the potential to exploit conserved genetic alterations, which may increase the efficacy of these targeted therapies. Predictive and prognostic biomarkers are urgently needed to maximize therapeutic efficacy and safety of these promising new treatments options in prostate cancer.

SPEDE-sampler: An R Shiny application to assess how methodological choices and taxon sampling can affect Generalized Mixed Yule Coalescent output and interpretation.

Species delimitation tools are vital to taxonomy and the discovery of new species. These tools can make use of genetic data to estimate species boundaries, where one of the most widely used methods is the Generalized Mixed Yule Coalescent (GMYC) model. Despite its popularity, a number of factors are known to influence the performance and resulting inferences of the GMYC. Moreover, the few studies that have assessed model performance to date have been predominantly based on simulated data sets, where model assumptions are not violated. Here, we present a user-friendly R Shiny application, 'SPEDE-sampler' (SPEcies DElimitation sampler), that assesses the effect of computational and methodological choices, in combination with sampling effects, on the GMYC model. Output phylogenies are used to test the effect that (1) sample size, (2) BEAST and GMYC parameters (e.g. prior settings, single vs multiple threshold, clock model), and (3) singletons have on GMYC output. Optional predefined grouping information (e.g. morphospecies/ecotypes) can be uploaded in order to compare it with GMYC species and estimate percentage match scores. Additionally, predefined groups that contribute to inflated species richness estimates are identified by SPEDE-sampler, allowing for the further investigation of potential cryptic species or geographical substructuring in those groups. Merging by the GMYC is also recorded to identify where traditional taxonomy has overestimated species numbers. Four worked examples are provided to illustrate the functionality of the program's workflow, and the variation that can arise when applying the GMYC model to empirical data sets. The R Shiny program is available for download at https://github.com/clarkevansteenderen/spede_sampler_R.

Role of ultrasonography in the diagnosis of temporal arteritis.

BACKGROUND: Temporal artery (TA) biopsy is the current standard for diagnosing temporal arteritis, but has limited sensitivity. Colour duplex ultrasonography is a newer, non-invasive method of diagnosing temporal arteritis. METHODS: A systematic review was performed of trials comparing TA biopsy with duplex ultrasonography. Duplex results (halo sign, stenosis or vessel occlusion) were compared with either TA biospy findings or the American College of Rheumatology research criteria for diagnosing temporal arteritis. Trials were identified from MEDLINE, Embase and the Cochrane Library trials register. The performance of duplex ultrasonography was assessed with weighted independent sensitivity and specificity values, and summary receiver operating characteristic curve analysis. RESULTS: There were 17 eligible studies containing 998 patients. When the halo sign on duplex imaging was compared with TA biopsy, the sensitivity was 75 (95 per cent confidence interval 67 to 82) per cent and the specificity was 83 (78 to 88) per cent. There was no heterogeneity across the eligible studies. CONCLUSION: Duplex ultrasonography was relatively accurate for diagnosing temporal arteritis. It should become the first-line investigation, with biopsy reserved for patients with a negative scan.

Targeted mapping of Cdu1, a major locus regulating grain cadmium concentration in durum wheat (Triticum turgidum L. var durum).

Some durum wheat (Triticum turgidum L. var durum) cultivars have the genetic propensity to accumulate cadmium (Cd) in the grain. A major gene controlling grain Cd concentration designated as Cdu1 has been reported on 5B, but the genetic factor(s) conferring the low Cd phenotype are currently unknown. The objectives of this study were to saturate the chromosomal region harboring Cdu1 with newly developed PCR-based markers and to investigate the colinearity of this wheat chromosomal region with rice (Oryza sativa L.) and Brachypodium distachyon genomes. Genetic mapping of markers linked to Cdu1 in a population of recombinant inbred substitution lines revealed that the gene(s) associated with variation in Cd concentration resides in wheat bin 5BL9 between fraction breakpoints 0.76 and 0.79. Genetic mapping and quantitative trait locus (QTL) analysis of grain Cd concentration was performed in 155 doubled haploid lines from the cross W9262-260D3 (low Cd) by Kofa (high Cd) revealed two expressed sequence tag markers (ESMs) and one sequence tagged site (STS) marker that co-segregated with Cdu1 and explained >80% of the phenotypic variation in grain Cd concentration. A second, minor QTL for grain Cd concentration was also identified on 5B, 67 cM proximal to Cdu1. The Cdu1 interval spans 286 kbp of rice chromosome 3 and 282 kbp of Brachypodium chromosome 1. The markers and rice and Brachypodium colinearity described here represent tools that will assist in the positional cloning of Cdu1 and can be used to select for low Cd accumulation in durum wheat breeding programs targeting this trait. The isolation of Cdu1 will further our knowledge of Cd accumulation in cereals as well as metal accumulation in general.

Anaesthetic specialisation leads to improved early- and medium-term survival following major vascular surgery.

OBJECTIVE: Vascular surgical specialisation is associated with improved outcomes. We aimed to assess the effect of anaesthetic specialisation on outcome following major vascular surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing major vascular surgery (lower limb revascularisation, elective and ruptured abdominal aortic aneurysm repair, endovascular aneurysm repair and carotid endarterectomy) over a five-year period were identified from a prospective database. The primary outcomes were death within 30 days and death within two years of surgery. Potential risk factors for mortality were assessed using multivariate logistic regression modelling. RESULTS: The analysis cohort comprised 1155 patients followed up for a median of 583 days. Mortality within two years of surgery was 16%. For the overall cohort, care from vascular anaesthetists was independently associated with reduced 30-day (odds ratio 0.22; 95% CI 0.12-0.62) and medium-term mortality (0.31; 95% CI 0.18-0.55). For elective patients (n=851), vascular anaesthesia reduced two-year mortality (odds ratio 0.29; 95% CI 0.15-0.58; P=0.0004) though not 30-day mortality (odds ratio 0.55; 95% CI 0.15-1.95; P=0.35). For emergency patients, care by a vascular anaesthetist influenced neither 30-day mortality (odds ratio 0.33; 95% CI 0.08-1.41; P=0.13) nor medium-term mortality (odds ratio 0.45; 95% CI 0.17-1.21; P=0.11). CONCLUSIONS: Anaesthetic specialisation reduced early- and medium-term mortality rates following major vascular surgery. If replicated by prospective studies, these results suggest that vascular surgery services would benefit from specialised anaesthetic support.

Allelic variation at Psy1-A1 and association with yellow pigment in durum wheat grain.

The yellow pigment (YP) of durum wheat (Triticum turgidum L. var durum) semolina is due in part to the presence of carotenoid pigments found in the endosperm and is an important end-use quality trait. Phytoene synthase (Psy) is considered a rate-limiting enzyme in the carotenoid biosynthetic pathway and in this study, three alleles of Psy1-A1 were sequenced from four durum wheat cultivars and a co-dominant marker was developed for genetic mapping. Psy1-A1 mapped to chromosome 7AL near Xwmc809 in three durum mapping populations and was significantly associated with a pigment quantitative trait loci (QTL) identified on that chromosome. A second QTL localized 25 cM proximal to Psy1-A1 in two populations, and the interaction between the two QTL was not significant. Consistent with QTL mapping data, the Psy1-A1o allele was associated with elevated pigment in a validation population comprising 93 diverse cultivars and breeding lines. These results confirm an earlier hypothesis that Psy1, and at least one additional gene in the distal region of 7AL, are associated with grain YP differences in durum wheat. The functional co-dominant marker developed in this study differentiates the Psy1-A1 alleles reported here and could be used as a target to enhance YP selection in durum wheat breeding programs.

Identification and validation of quantitative trait loci for grain protein concentration in adapted Canadian durum wheat populations.

Grain protein concentration (GPC) is one of the most important factors influencing pasta-making quality. Durum wheat (Triticum turgidum L. var durum) cultivars with high GPC produce pasta with increased tolerance to overcooking and greater cooked firmness. However, the large environmental effect on expression of GPC and the negative correlation with grain yield have slowed genetic improvement of this important trait. Understanding the genetics and identification of molecular markers associated with high GPC would aid durum wheat breeders in trait selection at earlier generations. The objectives of this study were to identify and validate molecular markers associated with quantitative trait loci (QTL) for elevated GPC in durum wheat. A genetic map was constructed using SSR and DArT markers in an F(1)-derived doubled haploid (DH) population derived from the cross DT695 x Strongfield. The GPC data were collected from replicated trials grown in six Canadian environments from 2002 to 2005. QTL associated with variation for GPC were identified on the group 1, 2, and 7 chromosomes and on 5B and 6B, but only QGpc.usw-B3 on 2B and QGpc.usw-A3 on 7A were expressed consistently in four and six environments, respectively. Positive alleles for GPC at these loci were contributed by the high-GPC parent Strongfield. The QGpc.usw-A3 QTL was validated in a second DH population, and depending on environment, selection for the Strongfield allele at barc108 resulted in +0.4% to +1.0% increase in GPC, with little effect on yield in most environments. Given the consistent expression pattern in multiple populations and environments, barc108 could be useful for marker-assisted selection for high GPC.

Chromosomal location of the cadmium uptake gene (Cdu1) in durum wheat.

Levels of the heavy metal cadmium (Cd) in food products are a food safety concern. Grain Cd is higher in durum (Triticum turgidum L. var. durum) than in common wheat, so reduction of Cd in durum grain is a priority of breeding programs. Previous research demonstrated that a single dominant gene, Cdu1, confers the low grain Cd phenotype, but the map location of the gene is not known. A doubled haploid population segregating for Cd concentration, developed from the cross of W9262-260D3 (a Kyle*2/Biodur inbred selection with low Cd uptake) and Kofa (high Cd uptake) and mapped with microsatellite markers, was used to locate Cdu1. Grain Cd concentration was determined by standard laboratory methods on field grain samples in 2000 and 2001. The Cd concentration segregated bimodally, allowing Cdu1 to be mapped qualitatively as well as quantitatively with quantitative trait locus analysis. The Cdu1 gene mapped to the long arm of chromosome 5B.

Selection and breeding of plant cultivars to minimize cadmium accumulation.

Natural variation occurs in the uptake and distribution of essential and nonessential trace elements among crop species and among cultivars within species. Such variation can be responsible for trace element deficiencies and toxicities, which in turn can affect the quality of food. Plant breeding can be an important tool to both increase the concentration of desirable trace elements and reduce that of potentially harmful trace elements such as cadmium (Cd). Selection programs for a low-Cd content of various crops, including durum wheat, sunflower, rice and soybean have been established and low-Cd durum wheat cultivars and sunflower hybrids have been developed. In durum wheat (Triticum turgidum L. var durum), low-Cd concentration is controlled by a single dominant gene. The trait is highly heritable, and incorporation of the low-Cd allele can help to reduce the average grain Cd to levels below proposed international limits. The allele for low-Cd concentration does not appear to affect major economic traits and should not cause problems when incorporated into durum cultivars. The cost of Cd selection in a breeding program is initially large both in terms of Cd determination and reduced progress towards development of other economic traits, but declines as more breeding lines in the program carry the low-Cd trait and are utilized in new crosses. Production of low-Cd crop cultivars can be used as a tool to reduce the risk of movement of Cd into the human diet.

Dose-response relationships for spironolactone in combination with a potassium-wasting diuretic.

The plasma and urine electrolyte responses to repeated doses of spironolactone, 25, 50, and 100 mg, in combination with metolazone, 2.5, 5.0, and 10 mg, were examined in 18 healthy subjects (six at each dose of metolazone). During the period of pharmacologic steady state, there were log linear spironolactone dose-response relationships for plasma potassium, sodium, and bicarbonate (P less than 0.001 in each case) with no contraindication to parallelism between the metolazone groups. In the absence of mineralocorticoid challenge, spironolactone dose-urine electrolyte responses could not be demonstrated. However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses. These observations suggest that a convenient bioassay for aldosterone antagonists in normal men may be provided by the electrolyte responses to repeated doses of such drugs in combination with potassium-wasting diuretics. In view of the limitations of other methods, this approach may have particular relevance to the evaluation of potassium-sparing properties.

Activity of sulfur-containing intermediate metabolites of spironolactone.

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.

Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison.

The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)-K was compared to that of spironolactone in two studies in healthy men. OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis. The best estimate of the relative potency of OH OPC(ME)-K: spironolactone (derived from a simple protocol using equal single doses of the two drugs) was 0.60:1 (95% confidence limits 0.24:1 to 1.42:1), in good agreement with the estimate from a more complex three-dose parallel-line bioassay (0.61:1, 95% confidence limits 0.48:1 to 0.79:1). The results of simple single-dose studies can be used, with certain assumptions, to provide a useful estimate of the relative potency of new aldosterone antagonists at an early stage of development.

Corpus callosum morphometry and dichotic listening performance: individual differences in functional interhemispheric inhibition?

We examined the relationship between midsagittal corpus callosum area, as seen by magnetic resonance imaging, and behavioral laterality effects from a dichotic listening task requiring cross-callosal relay of an auditory signal, in 60 healthy young adults. Four patients with complete forebrain commissurotomy were also given the dichotic listening task, confirming that in this task, the report of left ear items is dependent on callosal pathways. Contrary to our predictions, callosum measures were unrelated to either a laterality measure or to inferior (typically left) ear performance. Surprisingly, superior (typically right) ear accuracies, which do not depend on cross-callosal sensory transfer, were significantly and negatively correlated with callosum size. These findings show that normal variations in callosum size do not appear to contribute significantly to individual differences in hemispheric specialization. Callosum size may, instead, be associated with degree of functional interhemispheric inhibition.

A study of the possible role of mesothelium as a surface for flowing blood.

Mouse mesothelium has been examined as a surface for supporting blood flow. We have examined ten pieces of intact mesothelium and ten pieces of damaged mesothelium following 10 min exposure to flowing blood in a Baumgartner chamber. Scanning electron microscopy of the intact specimens demonstrated no adhering blood platelets, whereas the damaged specimens were found to be covered with large numbers of adhering platelets. In addition we have demonstrated that undamaged mesothelium does not appear to be morphologically altered after exposure to blood, and that undamaged mesothelium produces significantly more prostacyclin than damaged control. These findings support that mesothelial cells hold promise as a lining for prosthetic vascular implants.

The mesothelial cell as a non-thrombogenic surface.

A technique for harvesting mesothelial cells is described. This entails collagenase digestion of omentum after which the cells can be cultured. The technique has been developed using the rat, but has also been successfully applied to human tissue. Cultured rat mesothelial cells obtained in this way have been examined by scanning electron microscopy. Rat mesothelial cells grown on plastic film have been exposed to blood in an in vitro system using a Baumgartner chamber and have been demonstrated to support blood flow. No adhering platelets were observed on the mesothelial cell surface. Fibroblasts similarly exposed to blood as a control were washed off the plastic.

Spatio-temporal stages in face and word processing. 2. Depth-recorded potentials in the human frontal and Rolandic cortices.

Evoked potentials (EPs) were recorded directly from 650 frontal and peri-Rolandic sites in 26 subjects during face and/or word recognition, as well as during control tasks (simple auditory and visual discrimination). Electrodes were implanted in order to localize epileptogenic foci resistant to medication, and thus direct their surgical removal. While awaiting spontaneous seizure onset, the patients gave informed consent to perform cognitive tasks during intracerebral EEG recording. The earliest potentials appeared to be related to sensory stimulation, were prominent in lateral prefrontal cortex, and occurred at peak latencies of about 150 and 190 ms. A small triphasic complex beginning slightly later (peak latencies about 200-285-350 ms) appeared to correspond to the scalp N2-P3a-slow wave, associated with non-specific orienting. Multiple components peaking from 280 to 900 ms, and apparently specific to words were occasionally recorded in the left inferior frontal g, pars triangularis (Broca's area). Components peaking at about 430 and 600 ms were recorded in all parts of the prefrontal cortex, but were largest (up to 180 microV) and frequently polarity-inverted in the ventro-lateral prefrontal cortex. These components appeared to represent the N4-P3b, which have been associated with contextual integration and cognitive closure. Finally, a late negativity (650-900 ms) was recorded in precentral and premotor cortices, probably corresponding to a peri-movement readiness potential. In summary, EP components related to early sensory processing were most prominent in lateral prefrontal, to orienting in medial limbic, to word-specific processing in Broca's area, to cognitive integration in ventro-lateral prefrontal, and to response organization in premotor cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Spatio-temporal stages in face and word processing. I. Depth-recorded potentials in the human occipital, temporal and parietal lobes [corrected].

Evoked potentials (EPs) were used to help identify the timing, location, and intensity of the information-processing stages applied to faces and words in humans. EP generators were localized using intracranial recordings in 33 patients with depth electrodes implanted in order to direct surgical treatment of drug-resistant epilepsy. While awaiting spontaneous seizure onset, the patients gave their fully informed consent to perform cognitive tasks. Depth recordings were obtained from 1198 sites in the occipital, temporal and parietal cortices, and in the limbic system (amygdala, hippocampal formation and posterior cingulate gyrus). Twenty-three patients received a declarative memory recognition task in which faces of previously unfamiliar young adults without verbalizable distinguishing features were exposed for 300 ms every 3 s; 25 patients received an analogous task using words. For component identification, some patients also received simple auditory (21 patients) or visual (12 patients) discrimination tasks. Eight successive EP stages preceding the behavioral response (at about 600 ms) could be distinguished by latency, and each of 14 anatomical structures was found to participate in 2-8 of these stages. The earliest response, an N75-P105, focal in the most medial and posterior of the leads implanted in the occipital lobe (lingual g), was probably generated in visual cortical areas 17 and 18. These components were not visible in response to words, presumably because words were presented foveally. A focal evoked alpha rhythm to both words and faces was also noted in the lingual g. This was followed by an N130-P180-N240 focal and polarity-inverting in the basal occipitotemporal cortex (fusiform g, probably areas 19 and 37). In most cases, the P180 was evoked only by faces, and not by words, letters or symbols. Although largest in the fusiform g this sequence of potentials (especially the N240) was also observed in the supramarginal g, posterior superior and middle temporal g, posterior cingulate g, and posterior hippocampal formation. The N130, but not later components of this complex, was observed in the anterior hippocampus and amygdala. Faces only also evoked longer-latency potentials up to 600 ms in the right fusiform g. Words only evoked a series of potentials beginning at 190 ms and extending to 600 ms in the fusiform g and near the angular g (especially left). Both words and faces evoked a N150-P200-PN260 in the lingual g, and posterior inferior and middle temporal g.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomical-behavioral relationships: corpus callosum morphometry and hemispheric specialization.

We obtained midsagittal measures of the corpus callosum in 60 healthy young adults (right-handed and left-handed males and females), and examined whether individual differences in anatomical measures of callosal connectivity are related to behavioral laterality measures in the same subjects. In an attempt to tap functionally-distinct callosal "channels", four behavioral laterality tasks were used that differed in sensory modality (visual, auditory, tactile) and/or level of cognitive processing (sensory versus semantic). In addition, the tasks had both intrahemispheric and interhemispheric conditions. Sex differences were found for measures of the posterior body (i.e. isthmus) of the corpus callosum, which, in turn, interacted with handedness. In contrast, only handedness effects were found for the behavioral laterality measures. Anatomical-behavioral correlations did not disclose relationships between callosal size and performance on task conditions requiring sensory interhemispheric integration or transfer. Instead, the correlational findings are consistent with the view that the corpus callosum participates in such higher order "control" functions as the support of bilateral representation of language, functional interhemispheric inhibition, and the maintenance of hemispheric differences in arousal. This is consistent with the finding that regional callosal size is related to the number of small diameter fibers, which are presumed to interconnect homologous association cortices in the two hemispheres.