100 research outputs found

    Paths to Softlifting Intention

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    Voluntary corporate liquidations

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    This paper examines possible motives for and consequences of voluntary corporate liquidations. Specifically, the procedural and tax differences between voluntary liquidations and other control-changing transaction devices are analyzed. An empirical investigation of successful liquidations shows that the announcement of liquidation reduces the risk of liquidating shares, that the shareholders receive substantial gains from successful liquidations, and that the average gains to the acquiring shareholders are not significantly different from zero. These findings suggest that the liquidating firms' assets have been underutilized before liquidation and that voluntary liquidations lead to higher-valued reallocations of corporate resources.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26484/1/0000020.pd

    Swings and roundabouts: the vagaries of democratic consolidation and ‘electoral rituals’ in Sierra Leone

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    YesThe history of the electoral process in Sierra Leone is at the same time tortuous and substantial. From relatively open competitive multi-party politics in the 1960s, which led to the first turnover of power at the ballot box, through the de facto and de jure one-party era, which nonetheless had elements of electoral competition, and finally to contemporary post-conflict times, which has seen three elections and a second electoral turnover in 2007, one can discern evolving patterns. Evidence from the latest local and national elections in 2012 suggests that there is some democratic consolidation, at least in an electoral sense. However, one might also see simultaneous steps forward and backward – What you gain on the swings, you may lose on the roundabouts. This is particularly so in terms of institutional capacities, fraud and violence, and one would need to enquire of the precise ingredients – in terms of political culture or in other words the attitudes and motivations of electors and the elected – of this evolving Sierra Leonean, rather than specifically liberal type, of democracy. Equally, the development of ‘electoral rituals’, whether peculiar to Sierra Leone or not and whether deemed consolidatory or not, has something to say as part of an investigation into the electoral element of democratic consolidation.1 The literature on elections in Africa most often depicts a number of broad features, such as patronage, ethno-regionalism, fraud and violence, and it is the intention of this article to locate contemporary Sierra Leone, as precisely as possible, within the various strands of this discourse

    How common and severe are six withdrawal effects from, and addiction to, antidepressants? The experiences of a large international sample of patients

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    Introduction: The incidence and severity of withdrawal effects when coming off antidepressants (ADs) have recently received considerable attention. National guidelines on the topic have proven to be inaccurate. This paper reports the largest direct-to-patient international survey on these issues. Methods: Data generated by an online survey from 867 people from 31 countries, who had taken ADs continuously for at least one month, and had tried to come off (successfully or not) was analysed. Results: The majority (59%) had taken ADs for more than three years. Of those who were still taking them, 29% had been doing so for at least 20 years. 61% reported some degree of withdrawal effects, and 44% of these described the effects as ‘severe’. The most common of six listed withdrawal effects were anxiety/panic (66%) and irritability (62%). The most common spontaneously reported ‘other’ withdrawal effect was suicidality (2%). 40% reported that they felt addicted, with 39% of these describing their addiction as ‘severe’. Over half (55%) reported some degree of difficulty coming off, with 27% ticking ‘very difficult’, and 11% ‘very easy’. Duration of treatment was related to withdrawal, addiction and difficulty coming off. Younger people experienced more frequent withdrawal effects. Only six people (0.7%) recalled being told anything about withdrawal, dependence or addiction by the initial prescriber. Conclusions: These findings confirm previous studies, using a range of methodologies, finding high incidences of withdrawal effects, frequently at severe levels. National guidelines, and those of professional organisations, urgently need to be updated to reflect this evidence

    A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression

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    Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients’ treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group (P Conclusions Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone

    The developmental transcriptome for Lytechinus variegatus exhibits temporally punctuated gene expression changes

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    Embryonic development is arguably the most complex process an organism undergoes during its lifetime, and understanding this complexity is best approached with a systems-level perspective. The sea urchin has become a highly valuable model organism for understanding developmental specification, morphogenesis, and evolution. As a non-chordate deuterostome, the sea urchin occupies an important evolutionary niche between protostomes and vertebrates. Lytechinus variegatus (Lv) is an Atlantic species that has been well studied, and which has provided important insights into signal transduction, patterning, and morphogenetic changes during embryonic and larval development. The Pacific species, Strongylocentrotus purpuratus (Sp), is another well-studied sea urchin, particularly for gene regulatory networks (GRNs) and cis-regulatory analyses. A well-annotated genome and transcriptome for Sp are available, but similar resources have not been developed for Lv. Here, we provide an analysis of the Lv transcriptome at 11 timepoints during embryonic and larval development. Temporal analysis suggests that the gene regulatory networks that underlie specification are well-conserved among sea urchin species. We show that the major transitions in variation of embryonic transcription divide the developmental time series into four distinct, temporally sequential phases. Our work shows that sea urchin development occurs via sequential intervals of relatively stable gene expression states that are punctuated by abrupt transitions.National Science FoundationFirst author draf

    Examining sex differences in pleiotropic effects for depression and smoking using polygenic and gene‐region aggregation techniques

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    Sex differences in rates of depression are thought to contribute to sex differences in smoking initiation (SI) and number of cigarettes smoked per day (CPD). One hypothesis is that women smoke as a strategy to cope with anxiety and depression, and have difficulty quitting because of concomitant changes in hypothalamic–pituitary–adrenocortical (HPA) axis function during nicotine withdrawal states. Despite evidence of biological ties, research has not examined whether genetic factors that contribute to depression‐smoking comorbidity differ by sex. We utilized two statistical aggregation techniques—polygenic scores (PGSs) and sequence kernel association testing—to assess the degree of pleiotropy between these behaviors and moderation by sex in the Health and Retirement Study (N = 8,086). At the genome‐wide level, we observed associations between PGSs for depressive symptoms and SI, and measured SI and depressive symptoms (all p < .01). At the gene level, we found evidence of pleiotropy in FKBP5 for SI (p = .028), and sex‐specific pleiotropy in females in NR3C2 (p = .030) and CHRNA5 (p = .025) for SI and CPD, respectively. Results suggest bidirectional associations between depression and smoking may be partially accounted for by shared genetic factors, and genetic variation in genes related to HPA‐axis functioning and nicotine dependence may contribute to sex differences in SI and CPD.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150605/1/ajmgb32748.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150605/2/ajmgb32748_am.pd

    Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

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    Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR=0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR=0.022, opposite direction of effect). Conclusions: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP

    The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

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    Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

    Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

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    publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc
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