The Maudsley Early Onset Schizophrenia Study:The effect of age of onset and illness duration on fronto-parietal gray matter

Objective: In Early Onset Schizophrenia (EOS; onset before the 18th birthday) late brain maturational changes may interact with disease mechanisms leading to a wave of back to front structural changes during adolescence. To further explore this effect we examined the relationship between age of onset and duration of illness on brain morphology in adolescents with EOS. Subjects and methods: Structural brain magnetic resonance imaging scans were obtained from 40 adolescents with EOS. We used Voxel Based Morphometry and multiple regressions analyses, implemented in SPM, to examine the relationship between gray matter volume with age of onset and illness duration. Results: Age of onset showed a positive correlation with regional gray matter volume in the right superior parietal lobule (Brodmann Area 7). Duration of illness was inversely related to regional gray matter volume in the left inferior frontal gyrus (BA 11/47). Conclusions: Parietal gray matter loss may contribute to the onset of schizophrenia while orbitofrontal gray matter loss is associated with illness duration. © 2008 Elsevier Masson SAS. All rights reserved.

Relationship between sunlight and the age of onset of bipolar disorder:an international multisite study

Background - The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Methods - Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. Results - There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Limitations - Recall bias for onset and family history data. Conclusions - A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Influence of light exposure during early life on the age of onset of bipolar disorder

Background: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4N and 70.7N, and 1.2S and 41.3S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. Results: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Countering the trend towards careerist orientation in the age of downsizing:test of a social exchange model

Predicated on the assumption that employee careerist orientation resulting from organizational actions to cut costs constitutes a potential threat to their long-term profitability and success, this study proposed and tested a social exchange model of careerist orientation in the People's Republic of China. Specifically, it was hypothesized that organizational justice and career growth opportunities will be related to careerist orientation, but the relationship will be mediated by trust in employer. Structural equation modeling results provided support for the model. Trust in organization fully mediated the relationship between careerist orientation and its antecedents.

Wideband inhibition modulates the effect of onset asynchrony as a grouping cue

Onset asynchrony is arguably the most powerful grouping cue for the separation of temporally overlapping sounds (see Bregman 1990). A component that begins only 30–50 ms before the others makes a greatly reduced contribution to the timbre of a complex tone, or to the phonetic quality of a vowel (e.g. Darwin 1984). This effect of onset asynchrony does not necessarily imply a cognitive grouping process; instead it may result from peripheral adaptation in the response to the leading component in the few tens of milliseconds before the other components begin (e.g., Westerman and Smith 1984). However, two findings suggest that the effect of onset asynchrony cannot be explained entirely by peripheral adaptation. First, though the effect is smaller, the contribution of a component to the phonetic quality of a short-duration vowel is reduced when it ends after the other components (Darwin and Sutherland 1984; Roberts and Moore 1991).

Contralateral influences of wideband inhibition on the effect of onset asynchrony as a cue for auditory grouping

Onset asynchrony is an important cue for segregating sound mixtures. A harmonic of a vowel that begins before the other components contributes less to vowel quality. This asynchrony effect can be partly reversed by accompanying the leading portion of the harmonic with an octave-higher captor tone. The original interpretation was that the captor and leading portion formed a perceptual group, but it has recently been shown that the captor effect depends on neither a common onset time nor harmonic relations with the leading portion. Instead, it has been proposed that the captor effect depends on wideband inhibition in the central auditory system. Physiological evidence suggests that such inhibition occurs both within and across ears. Experiment 1 compared the efficacy of a pure-tone captor presented in the same or opposite ear to the vowel and leading harmonic. Contralateral presentation was at least as effective as ipsilateral presentation. Experiment 2 used multicomponent captors in a more comprehensive evaluation of harmonic influences on captor efficacy. Three captors with different fundamental frequencies were used, one of which formed a consecutive harmonic series with the leading harmonic. All captors were equally effective, irrespective of the harmonic relationship. These findings support and refine the inhibitory account. © 2007 Acoustical Society of America.

The influence of adaptation and inhibition on the effects of onset asynchrony on auditory grouping

Onset asynchrony is an important cue for auditory scene analysis. For example, a harmonic of a vowel that begins before the other components contributes less to the perceived phonetic quality. This effect was thought primarily to involve high-level grouping processes, because the contribution can be partly restored by accompanying the leading portion of the harmonic (precursor) with a synchronous captor tone an octave higher, and hence too remote to influence adaptation of the auditory-nerve response to that harmonic. However, recent work suggests that this restoration effect arises instead from inhibitory interactions relatively early in central auditory processing. The experiments reported here have reevaluated the role of adaptation in grouping by onset asynchrony and explored further the inhibitory account of the restoration effect. Varying the frequency of the precursor in the range ± 10% relative to the vowel harmonic (Experiment 1), or introducing a silent interval from 0 to 320 ms between the precursor and the vowel (Experiment 2), both produce effects on vowel quality consistent with those predicted from peripheral adaptation or recovery from it. However, there were some listeners for whom even the smallest gap largely eliminated the effect of the precursor. Consistent with the inhibitory account of the restoration effect, a contralateral pure tone whose frequency is close to that of the precursor is highly effective at restoring the contribution of the asynchronous harmonic (Experiment 3). When the frequencies match, lateralization cues arising from binaural fusion of the precursor and contralateral tone may also contribute to this restoration. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Public administration in an age of austerity:the future of the discipline

Reflecting changes in the nature of governance, some have questioned whether Public Administration is now an historical anachronism. While a legitimate debate exists between sceptics and optimists, this special issue demonstrates grounds for optimism by indicating the continuing diversity and adaptability of the field of Public Administration. In this introduction, we first sketch the variety of intellectual traditions which comprise the field of modern Public Administration. We then consider institutional challenges facing the subject given considerable pressures towards disciplinary fragmentation, and ideological challenges arising from a new distrust of public provision in the UK. Despite these challenges, Public Administration continues to provide a framework to analyse the practice of government and governance, governing institutions and traditions, and their wider sociological context. It can also directly inform policy reform - even if this endeavour can have its own pitfalls and pratfalls for the 'engaged' academic. We further suggest that, rather than lacking theoretical rigour, new approaches are developing that recognise the structural and political nature of the determinants of public administration. Finally, we highlight the richness of modern comparative work in Public Administration. Researchers can usefully look beyond the Atlantic relationship for theoretical enhancement and also consider more seriously the recursive and complex nature of international pressures on public administration. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Development of visual evoked responses to tritan,red-green and luminance stimuli in human infants

The principal aim of this work was to investigate the development of the S-cone colour-opponent pathway in human infants aged 4 weeks to 6 months. This was achieved by recording transient visual evoked responses to pattern-onset stimuli along a tritanopic confusion axis (tritan stimuli) at and around the adult isoluminant match. For comparison, visual evoked responses to red-green and luminance-modulated stimuli were recorded from the same infants at the same ages. Evoked responses were also recorded from colour-normal adults for comparison with those of the infants. The transient VEP allowed observation of response morphology as luminance differences were introduced to the chromatic stimuli. In this way, an estimate of isoluminance was possible in infants. Estimated isoluminant points for a group of six infants aged 6 to 10 weeks closely approximated the adult isoluminant match. This finding has implications for the use of photometric isoluminance in infant work, and suggests that photopic spectral sensitivity is similar in infants and adults. Abnormalities of the visual evoked responses to tritan, red-green and luminance-modulated stimuli in an infant with cystic fibrosis are reported. The results suggest abnormal function of the retino-striate visual pathway in this infant, and it is argued that these may be secondary to his illness, although data from more infants with cystic fibrosis are needed to clarify this further. A group of nine healthy infants demonstrated evoked responses to tritan stimuli by 4 to 10 weeks and to red-green stimuli by 6 to 11 weeks post-term age. Responses to luminance-modulated stimuli were present in all nine infants at the earliest age tested, namely 4 weeks post-term. The slightly earlier age of onset of evoked responses to tritan stimuli than for red-green may be explained by the relatively lower cone contrast afforded by red-green stimuli. Latency of the evoked response to both types of chromatic stimuli and to luminance-modulated stimuli decreased with age at a similar rate, suggesting that the visual pathways transmitting luminance and chromatic information mature at similar rates in young infants.

Start-up financing in the age of globalization

The authors investigate the determinants of start-up financing in fifty-four countries, using the Global Entrepreneurship Monitor (GEM) surveys for the years 2001-6. They find that financial liberalization increases the total financial size of the individual start-up entrepreneurial project both via the increased use of external and of own funds. In addition, the volume of start-up finance responds positively to international capital inflows, as represented by loans from nonresident banks and remittances, and negatively to the volume of offshore deposits. The positive impact of remittances on total volume of start-up financing is via financing by the entrepreneur.

Living with uncertainty in the age of runtime models

Uncertainty can be defined as the difference between information that is represented in an executing system and the information that is both measurable and available about the system at a certain point in its life-time. A software system can be exposed to multiple sources of uncertainty produced by, for example, ambiguous requirements and unpredictable execution environments. A runtime model is a dynamic knowledge base that abstracts useful information about the system, its operational context and the extent to which the system meets its stakeholders' needs. A software system can successfully operate in multiple dynamic contexts by using runtime models that augment information available at design-time with information monitored at runtime. This chapter explores the role of runtime models as a means to cope with uncertainty. To this end, we introduce a well-suited terminology about models, runtime models and uncertainty and present a state-of-the-art summary on model-based techniques for addressing uncertainty both at development- and runtime. Using a case study about robot systems we discuss how current techniques and the MAPE-K loop can be used together to tackle uncertainty. Furthermore, we propose possible extensions of the MAPE-K loop architecture with runtime models to further handle uncertainty at runtime. The chapter concludes by identifying key challenges, and enabling technologies for using runtime models to address uncertainty, and also identifies closely related research communities that can foster ideas for resolving the challenges raised. © 2014 Springer International Publishing.

Creutzfeldt-Jakob disease and vision

This review describes a group of diseases known as the transmissible spongiform encephalopathies (TSEs), which affect animals and humans. Examination of affected brain tissue suggests that these diseases are caused by the acquisition and deposition of prion protein (PrP). Creutzfeldt-Jakob disease (CJD) is the most important form of TSE in humans with at least four different varieties of the disease. Variant CJD (vCJD), a new form of the disease found in the UK, has several features that differ from the classical forms including early age of onset, longer duration of disease, psychiatric presentation (for example, depression) and extensive florid plaque development in the brain. About 10 per cent of patients with CJD exhibit visual symptoms at disease presentation and approximately 50 per cent during the course of the disease. The most commonly reported visual symptoms include diplopia, supranuclear palsies, complex visual disturbances, homonymous visual field defects, hallucinations and cortical blindness. Saccadic and smooth pursuit movements appear to be more rarely affected. The agent causing vCJD accumulates in lymphoid tissue such as the spleen and tonsils. The cornea has lymphoid tissue in the form of corneal dendritic cells that are important in the regulation of the immune response in the anterior segment of the eye. The presence of these cells in the cornea has raised the possibility of transmission between patients via optical devices that contact the eye. Although such transmission is theoretically possible it remains highly improbable.