Advances in laboratory testing for thrombophilia

Testing for hereditary thrombophilia typically includes tests for activated protein C resistance (APC-R) and/or factor V Leiden, protein C, protein S, antithrombin, and prothrombin G20210A. New options for these assays have become available in recent years, with different advantages and disadvantages among the currently available methods. Potential interferences for each assay type are discussed, including lupus anticoagulants, heparin, warfarin, direct thrombin inhibitors (such as argatroban, dabigatran, hirudin, or bivalirudin), rivaroxaban, factor deficiencies or elevations, factor V Leiden, and specific mutations that the assay(s) might not be able to detect. Causes of acquired deficiencies are also described, as these must be carefully excluded before diagnosing a hereditary deficiency of protein C, protein S, or antithrombin.     

Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and Afghanistan war veterans

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non‐TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter‐specific registration followed by whole‐brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with “feeling dazed or confused,” but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast‐ and impact‐related mild TBI that involves a cascade of inflammatory and neurochemical events. Hum Brain Mapp 34:2986–2999, 2013. © 2012 Wiley Periodicals, Inc.     

Atypical brain activation patterns during a face‐to‐face joint attention game in adults with autism spectrum disorder

Joint attention behaviors include initiating one's own and responding to another's bid for joint attention to an object, person, or topic. Joint attention abilities in autism are pervasively atypical, correlate with development of language and social abilities, and discriminate children with autism from other developmental disorders. Despite the importance of these behaviors, the neural correlates of joint attention in individuals with autism remain unclear. This paucity of data is likely due to the inherent challenge of acquiring data during a real‐time social interaction. We used a novel experimental set‐up in which participants engaged with an experimenter in an interactive face‐to‐face joint attention game during fMRI data acquisition. Both initiating and responding to joint attention behaviors were examined as well as a solo attention (SA) control condition. Participants included adults with autism spectrum disorder (ASD) (n = 13), a mean age‐ and sex‐matched neurotypical group (n = 14), and a separate group of neurotypical adults (n = 22). Significant differences were found between groups within social‐cognitive brain regions, including dorsal medial prefrontal cortex (dMPFC) and right posterior superior temporal sulcus (pSTS), during the RJA as compared to SA conditions. Region‐of‐interest analyses revealed a lack of signal differentiation between joint attention and control conditions within left pSTS and dMPFC in individuals with ASD. Within the pSTS, this lack of differentiation was characterized by reduced activation during joint attention and relative hyper‐activation during SA. These findings suggest a possible failure of developmental neural specialization within the STS and dMPFC to joint attention in ASD. Hum Brain Mapp 34:2511–2523, 2013. © 2012 Wiley Periodicals, Inc.     

The Influence of refractoriness upon comprehension of non-verbal auditory stimuli

An investigation of non-verbal auditory comprehension in two patients with global aphasia following stroke is reported. The primary aim of the investigation was to establish whether refractory access disorders can affect non-verbal input modalities. All previous reports of refractoriness, a cognitive syndrome characterized by response inconsistency, sensitivity to temporal factors and insensitivity to item frequency, have involved comprehension tasks which have a verbal component. Two main experiments are described. The first consists of a novel sound-to-picture and sound-to-word matching task in which comprehension of environmental sounds is probed under conditions of semantic relatedness and semantic unrelatedness. In addition to the two stroke patients, the performance of a group of 10 control patients with non-vascular pathology is reported, along with evidence of semantic relatedness effects in sound comprehension. The second experiment examines environmental sound comprehension within a repetitive probing paradigm which affords assessment of the effects of semantic relatedness, response consistency and presentation rate. It is demonstrated that the two stroke patients show a significant increase in error rate across multiple probes of the same set of sound stimuli, indicating the presence of refractoriness within this non-verbal domain. The implications of the results are discussed with reference to our current understanding of the mechanisms of refractoriness.     

Physical occupational exposures during working life and quality of life after labour market exit: results from the GAZEL study

Objective: To investigate variations in quality of life at older ages, we take a life course perspective to analyse long-term effects of physical working conditions upon quality of life after retirement. In doing so, we study to what extent these associations are explained by individuals’ health at older ages.

Method: We use administrative data and self-administered questionnaire responses from the French GAZEL cohort. Quality of life was assessed with CASP-19 in 2009 and related to three types of physical working conditions during previous working life: (1) ergonomic strain, (2) physical danger and (3) exposures to chemicals. Health was assessed in 2007 with the SF-36 Health Survey. Multiple regressions were calculated in retired men only, controlling for important confounders including social position.

Results: In contrast to men, few women were exposed to strenuous and dangerous working conditions in this cohort and were not included in subsequent analyses. Negative effects on retired men's quality of life were found for the physical occupational exposures of ergonomic strain and physical danger, but not for chemical exposures. Effects were attenuated after the introduction of physical and mental health to the models, indicating an indirect effect of physical working conditions upon quality of life via health.

Conclusion: Adverse physical working conditions have long-term consequences for health and quality of life at older ages. Improvements to physical working conditions may improve individuals’ quality of life over the long term.