Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response

OBJECTIVE: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. METHOD: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. RESULTS: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. CONCLUSIONS: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

The British state and the Irish rebellion of 1916: an intelligence failure or an failure of response

The teleological narrative that has dominated the handling of intelligence by the British state in the events that led up to the 1916 Irish Rebellion in Dublin has been characterised as a cocktail of incompetence and mendacity. Using new and existing archive material this article argues that both the cabinet in London and key members of the Irish Executive in Dublin were supplied with accurate and timely intelligence by the Admiralty's signals intelligence unit, the Royal Irish Constabulary and the Dublin Metropolitan Police with respect to this event. Far from being a failure of intelligence here is evidence to show that there occurred a failure of response on behalf of key decision-makers. The warnings that were given by intelligence organisations were filtered through the existing policy preferences and assumptions. As a result of these factors accurate evaluations and sound judgement were not exercised by key officials, such as Sir Matthew Nathan, in Dublin Castle.

Modeling Coulombic failure of sea ice with leads

[1] Sea ice failure under low-confinement compression is modeled with a linear Coulombic criterion that can describe either fractural failure or frictional granular yield along slip lines. To study the effect of anisotropy we consider a simplified anisotropic sea ice model where the sea ice thickness depends on orientation. Accommodation of arbitrary deformation requires failure along at least two intersecting slip lines, which are determined by finding two maxima of the yield criterion. Due to the anisotropy these slip lines generally differ from the standard, Coulombic slip lines that are symmetrically positioned around the compression direction, and therefore different tractions along these slip lines give rise to a nonsymmetric stress tensor. We assume that the skewsymmetric part of this tensor is counterbalanced by an additional elastic stress in the sea ice field that suppresses floe spin. We consider the case of two leads initially formed in an isotropic ice cover under compression, and address the question of whether these leads will remain active or new slip lines will form under a rotation of the principal compression direction. Decoupled and coupled models of leads are considered and it is shown that for this particular case they both predict lead reactivation in almost the same way. The coupled model must, however, be used in determining the stress as the decoupled model does not resolve the stress asymmetry properly when failure occurs in one lead and at a new slip line.

Success and failure of grassroots innovations for addressing climate change: the case of the Transition Movement

Grassroots innovations emerge as networks generating innovative solutions for climate change adaptation and mitigation. However, it is unclear if grassroots innovations can be successful in responding to climate change. Little evidence exists on replication, international comparisons are rare, and research tends to overlook discontinued responses in favour of successful ones. We take the Transition Movement as a case study of a rapidly spreading transnational grassroots network, and include both active and non-active local transition initiatives. We investigate the replication of grassroots innovations in different contexts with the aim to uncover general patterns of success and failure, and identify questions for future research. An online survey was carried out in 23 countries (N=276). The data analysis entailed testing the effect of internal and contextual factors of success as drawn from the existing literature, and the identification of clusters of transition initiatives with similar internal and contextual factor configurations. Most transition initiatives consider themselves successful. Success is defined along the lines of social connectivity and empowerment, and external environmental impact. We find that less successful transition initiatives might underestimate the importance of contextual factors and material resources in influencing success. We also find that their diffusion is linked to the combination of local-global learning processes, and that there is an incubation period during which a transition initiative is consolidated. Transition initiatives seem capable of generalising organisational principles derived from unique local experiences that seem to be effective in other local contexts. However, the geographical locations matter with regard to where transition initiatives take root and the extent of their success, and ‘place attachment’ may have a role in the diffusion of successful initatives. We suggest that longitudinal comparative studies can advance our understanding in this regard, as well as inform the changing nature of the definition of success at different stages of grassroots innovation development, and the dynamic nature of local and global linkages.

Civilian casualties – do we really care? The failure of the revolution in military affairs of non-lethal weapons in the U.S., Russia and Israel

Causing civilian casualties during military operations has become a much politicised topic in international relations since the Second World War. Since the last decade of the 20th century, different scholars and political analysts have claimed that human life is valued more and more among the general international community. This argument has led many researchers to assume that democratic culture and traditions, modern ethical and moral issues have created a desire for a world without war or, at least, a demand that contemporary armed conflicts, if unavoidable, at least have to be far less lethal forcing the military to seek new technologies that can minimise civilian casualties and collateral damage. Non-Lethal Weapons (NLW) – weapons that are intended to minimise civilian casualties and collateral damage – are based on the technology that, during the 1990s, was expected to revolutionise the conduct of warfare making it significantly less deadly. The rapid rise of interest in NLW, ignited by the American military twenty five years ago, sparked off an entirely new military, as well as an academic, discourse concerning their potential contribution to military success on the 21st century battlefields. It seems, however, that except for this debate, very little has been done within the military forces themselves. This research suggests that the roots of this situation are much deeper than the simple professional misconduct of the military establishment, or the poor political behaviour of political leaders, who had sent them to fight. Following the story of NLW in the U.S., Russia and Israel this research focuses on the political and cultural aspects that have been supposed to force the military organisations of these countries to adopt new technologies and operational and organisational concepts regarding NLW in an attempt to minimise enemy civilian casualties during their military operations. This research finds that while American, Russian and Israeli national characters are, undoubtedly, products of the unique historical experience of each one of these nations, all of three pay very little regard to foreigners’ lives. Moreover, while it is generally argued that the international political pressure is a crucial factor that leads to the significant reduction of harmed civilians and destroyed civilian infrastructure, the findings of this research suggest that the American, Russian and Israeli governments are well prepared and politically equipped to fend off international criticism. As the analyses of the American, Russian and Israeli cases reveal, the political-military leaderships of these countries have very little external or domestic reasons to minimise enemy civilian casualties through fundamental-revolutionary change in their conduct of war. In other words, this research finds that employment of NLW have failed because the political leadership asks the militaries to reduce the enemy civilian casualties to a politically acceptable level, rather than to the technologically possible minimum; as in the socio-cultural-political context of each country, support for the former appears to be significantly higher than for the latter.

Likelihood estimate of treatment effects under selection bias

We consider methods for estimating causal effects of treatment in the situation where the individuals in the treatment and the control group are self selected, i.e., the selection mechanism is not randomized. In this case, simple comparison of treated and control outcomes will not generally yield valid estimates of casual effects. The propensity score method is frequently used for the evaluation of treatment effect. However, this method is based onsome strong assumptions, which are not directly testable. In this paper, we present an alternative modeling approachto draw causal inference by using share random-effect model and the computational algorithm to draw likelihood based inference with such a model. With small numerical studies and a real data analysis, we show that our approach gives not only more efficient estimates but it is also less sensitive to model misspecifications, which we consider, than the existing methods.

Comparison of treatment of incomplete abortion with misoprostol by physicians and midwives at district level in Uganda : a randomised controlled equivalence trial

BACKGROUND: Misoprostol is established for the treatment of incomplete abortion but has not been systematically assessed when provided by midwives at district level in a low-resource setting. We investigated the effectiveness and safety of midwives diagnosing and treating incomplete abortion with misoprostol, compared with physicians. METHODS: We did a multicentre randomised controlled equivalence trial at district level at six facilities in Uganda. Eligibility criteria were women with signs of incomplete abortion. We randomly allocated women with first-trimester incomplete abortion to clinical assessment and treatment with misoprostol either by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and was stratified for study site. Primary outcome was complete abortion not needing surgical intervention within 14-28 days after initial treatment. The study was not masked. Analysis of the primary outcome was done on the per-protocol population with a generalised linear-mixed effects model. The predefined equivalence range was -4% to 4%. The trial was registered at ClinicalTrials.gov, number NCT01844024. FINDINGS: From April 30, 2013, to July 21, 2014, 1108 women were assessed for eligibility. 1010 women were randomly assigned to each group (506 to midwife group and 504 to physician group). 955 women (472 in the midwife group and 483 in the physician group) were included in the per-protocol analysis. 452 (95·8%) of women in the midwife group had complete abortion and 467 (96·7%) in the physician group. The model-based risk difference for midwife versus physician group was -0·8% (95% CI -2·9 to 1·4), falling within the predefined equivalence range (-4% to 4%). The overall proportion of women with incomplete abortion was 3·8% (36/955), similarly distributed between the two groups (4·2% [20/472] in the midwife group, 3·3% [16/483] in the physician group). No serious adverse events were recorded. INTERPRETATION: Diagnosis and treatment of incomplete abortion with misoprostol by midwives is equally safe and effective as when provided by physicians, in a low-resource setting. Scaling up midwives' involvement in treatment of incomplete abortion with misoprostol at district level would increase access to safe post-abortion care. FUNDING: The Swedish Research Council, Karolinska Institutet, and Dalarna University.

The failure of early-stage technology startups in Brazil: a study about the contributing factors to the early-death of startups between 2009 and 2014 in Southeastern Brazil

This research aimed to find out which are the main factors that lead technology startups to fail. The study focused on companies located in the Southeast region of Brazil that operated between 2009 and 2014. In the beginning, a review of the literature was done to have a better understanding of basic concepts of entrepreneurship as well as modern techniques for developing entrepreneurship. Furthermore, an analysis of the entrepreneurial scenario in Brazil, with a focus on the Southeast, was also done. After this phase, the qualitative study began, in which 24 specialists from startups were interviewed and asked about which factors were crucial in leading a technology startup to fail. After analyzing the results, four main factors were identified and these factors were validated through a quantitative survey. A questionnaire was then formulated based on the answers from the respondents and distributed to founders and executives of startups, which both failed and succeeded. The questionnaire was answered by 56 companies and their answers were treated with the factor analysis statistical method to check the validity of the questionnaire. Finally, the logistical regression method was used to know the extent to which the factors led to the startups’ failure. In the end, the results obtained suggest that the most significant factor that leads technology startups in southeastern Brazil to fail are problems with interpersonal relationship between partners or investors.

The adaptive compensations in endocrine pancreas from glucocorticoid-treated rats are reversible after the interruption of treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)