Pituitary volume in patients with bipolar disorder and their first-degree relatives

Background: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been reported in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have yielded inconsistent findings. In addition, the contribution of genetic factors to the pituitary changes in BD remains largely unknown. Method: We used MRI to investigate the pituitary volume in 29 remitted patients with BD, 49 of their first-degree relatives (of whom 15 had a diagnosis of Major Depressive Disorder), and 52 age- and gender-matched healthy controls. Results: BD patients had a significantly larger pituitary volume compared with their relatives and healthy controls. Pituitary volume did not differ between controls and healthy relatives or relatives diagnosed with major depression. Limitations: Direct measures of HPA function (i.e., hormonal levels) were not available. Conclusions: These findings suggest that enlarged pituitary volume is associated with disease expression but not genetic susceptibility to BD. © 2009 Elsevier B.V. All rights reserved.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with bipolar disorder and their relatives

Background: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. Methods: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. Limitations: Cross-sectional design. Results: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. Conclusions: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions. © 2010 Elsevier B.V.

Familial and disease specific abnormalities in the neural correlates of the Stroop Task in Bipolar Disorder

Patients with Bipolar Disorder (BD) perform poorly on tasks of selective attention and inhibitory control. Although similar behavioural deficits have been noted in their relatives, it is yet unclear whether they reflect dysfunction in the same neural circuits. We used functional magnetic resonance imaging and the Stroop Colour Word Task to compare task related neural activity between 39 euthymic BD patients, 39 of their first-degree relatives (25 with no Axis I disorders and 14 with Major Depressive Disorder) and 48 healthy controls. Compared to controls, all individuals with familial predisposition to BD, irrespective of diagnosis, showed similar reductions in neural responsiveness in regions involved in selective attention within the posterior and inferior parietal lobules. In contrast, hypoactivation within fronto-striatal regions, implicated in inhibitory control, was observed only in BD patients and MDD relatives. Although striatal deficits were comparable between BD patients and their MDD relatives, right ventrolateral prefrontal dysfunction was uniquely associated with BD. Our findings suggest that while reduced parietal engagement relates to genetic risk, fronto-striatal dysfunction reflects processes underpinning disease expression for mood disorders. © 2011 Elsevier Inc.

Dissociable brain structural changes associated with predisposition, resilience, and disease expression in bipolar disorder

Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states. Copyright © 2009 Society for Neuroscience.

The impact of drug information on the prescribing of drugs

Using prescription analyses and questionnaires, the way drug information was used by general medical practitioners during the drug adoption process was studied. Three new drugs were considered; an innovation and two 'me-too' products. The innovation was accepted by general practitioners via a contagion process, information passing among doctors. The 'me-too' preparations were accepted more slowly and by a process which did not include the contagion effect. 'Industrial' information such as direct mail was used more at the 'awareness' stage of the adoption process while 'professional' sources of information such as articles in medical journals were used more to evaluate a new product. It was shown that 'industrial' information was preferred by older single practice doctors who did not specialise, had a first degree only and who did not dispense their own prescriptions. Doctors were divided into early and late-prescribers by using the date they first prescribed the innovatory drug. Their approach to drug information sources was further studied and it was shown that the early-prescriber issued slightly more prescriptions per month, had a larger list size, read fewer journals and generally rated industrial sources of information more highly than late-prescribers. The prescribing habits of three consultant rheumatologists were analysed and compared with those of the general practitioners in the community which they served. Very little association was noted and the influence of the consultant on the prescribing habits of general practitioners was concluded to be low. The consultants influence was suggested to be of two components, active and passive; the active component being the most influential. Journal advertising and advertisement placement were studied for one of the 'me-too' drugs. It was concluded that advertisement placement should be based on the reading patterns of general practitioners and not on ad-hoc data gathered by representatives as was the present practice. A model was proposed relating the 'time to prescribe' a new drug to the variables suggested throughout this work. Four of these variables were shown to be significant. These were, the list size, the medical age of the prescriber, the number of new preparations prescribed in a given time and the number of partners in the practice.

Laboratory focussed learning of core electronic engineering concepts in the first year of an honours degree programme

In common with most universities teaching electronic engineering in the UK, Aston University has seen a shift in the profile of its incoming students in recent years. The educational background of students has moved away from traditional Alevel maths and science and if anything this variation is set to increase with the introduction of engineering diplomas. Another major change to the circumstances of undergraduate students relates to the introduction of tuition fees in 1998 which has resulted in an increased likelihood of them working during term time. This may have resulted in students tending to concentrate on elements of the course that directly provide marks contributing to the degree classification. In the light of these factors a root and branch rethink of the electronic engineering degree programme structures at Aston was required. The factors taken into account during the course revision were:. Changes to the qualifications of incoming students. Changes to the background and experience of incoming students. Increase in overseas students, some with very limited practical experience. Student focus on work directly leading to marks. Modular compartmentalisation of knowledge. The need for provision of continuous feedback on performance We discuss these issues with specific reference to a 40 credit first year electronic engineering course and detail the new course structure and evaluate the effectiveness of the changes. The new approach appears to have been successful both educationally and with regards to student satisfaction. The first cohort of students from the new course will graduate in 2010 and results from student surveys relating particularly to project and design work will be presented at the conference. © 2009 K Sugden, D J Webb and R P Reeves.

Point-by-point inscription of first-order fiber Bragg grating for C-band applications

The influence of the fiber geometry on the point-by-point inscription of fiber Bragg gratings using a femtosecond laser is highlighted. Fiber Bragg gratings with high spectral quality and strong first-order Bragg resonances within the C-band are achieved by optimizing the inscription process. Large birefringence (1.2×10-4) and high degree of polarizationdependent index modulation are observed in these gratings. Potential applications of these gratings in resonators are further illustrated.

Point-by-point inscription of first-order fiber Bragg grating for C-band applications

The influence of the fiber geometry on the point-by-point inscription of fiber Bragg gratings using a femtosecond laser is highlighted. Fiber Bragg gratings with high spectral quality and strong first-order Bragg resonances within the C-band are achieved by optimizing the inscription process. Large birefringence (1.2x10-4) and high degree of polarizationdependent index modulation are observed in these gratings. Potential applications of these gratings in resonators are further illustrated. © 2007 Optical Society of America.

Linear binocular combination of responses to contrast modulation:contrast-weighted summation in first- and second-order vision

Binocular combination for first-order (luminancedefined) stimuli has been widely studied, but we know rather little about this binocular process for spatial modulations of contrast (second-order stimuli). We used phase-matching and amplitude-matching tasks to assess binocular combination of second-order phase and modulation depth simultaneously. With fixed modulation in one eye, we found that binocularly perceived phase was shifted, and perceived amplitude increased almost linearly as modulation depth in the other eye increased. At larger disparities, the phase shift was larger and the amplitude change was smaller. The degree of interocular correlation of the carriers had no influence. These results can be explained by an initial extraction of the contrast envelopes before binocular combination (consistent with the lack of dependence on carrier correlation) followed by a weighted linear summation of second-order modulations in which the weights (gains) for each eye are driven by the first-order carrier contrasts as previously found for first-order binocular combination. Perceived modulation depth fell markedly with increasing phase disparity unlike previous findings that perceived first-order contrast was almost independent of phase disparity. We present a simple revision to a widely used interocular gain-control theory that unifies first- and second-order binocular summation with a single principle-contrast-weighted summation-and we further elaborate the model for first-order combination. Conclusion: Second-order combination is controlled by first-order contrast.

Degree of vertical integration and its buffering effects on political uncertainty

The focus of this study is on the governance decisions in a concurrent channels context, in the case of uncertainty. The study examines how a firm chooses to deploy its sales force in times of uncertainty, and the subsequent performance outcome of those deployment choices. The theoretical framework is based on multiple theories of governance, including transaction cost analysis (TCA), agency theory, and institutional economics. Three uncertainty variables are investigated in this study. The first two are demand and competitive uncertainty which are considered to be industry-level market uncertainty forms. The third uncertainty, political uncertainty, is chosen as it is an important dimension of institutional environments, capturing non-economic circumstances such as regulations and political systemic issues. The study employs longitudinal secondary data from a Thai hotel chain, comprising monthly observations from January 2007 – December 2012. This hotel chain has its operations in 4 countries, Thailand, the Philippines, United Arab Emirates – Dubai, and Egypt, all of which experienced substantial demand, competitive, and political uncertainty during the study period. This makes them ideal contexts for this study. Two econometric models, both deploying Newey-West estimations, are employed to test 13 hypotheses. The first model considers the relationship between uncertainty and governance. The second model is a version of Newey-West, using an Instrumental Variables (IV) estimator and a Two-Stage Least Squares model (2SLS), to test the direct effect of uncertainty on performance and the moderating effect of governance on the relationship between uncertainty and performance. The observed relationship between uncertainty and governance observed follows a core prediction of TCA; that vertical integration is the preferred choice of governance when uncertainty rises. As for the subsequent performance outcomes, the results corroborate that uncertainty has a negative effect on performance. Importantly, the findings show that becoming more vertically integrated cannot help moderate the effect of demand and competitive uncertainty, but can significantly moderate the effect of political uncertainty. These findings have significant theoretical and practical implications, and extend our knowledge of the impact on uncertainty significantly, as well as bringing an institutional perspective to TCA. Further, they offer managers novel insight into the nature of different types of uncertainty, their impact on performance, and how channel decisions can mitigate these impacts.