Genetic screening of 202 individuals with congenital limb malformations and requiring reconstructive surgery

BACKGROUND: Congenital limb malformations (CLMs) are common and present to a variety of specialties, notably plastic and orthopaedic surgeons, and clinical geneticists. The authors aimed to characterise causative mutations in an unselected cohort of patients with CLMs requiring reconstructive surgery. METHODS: 202 patients presenting with CLM were recruited. The authors obtained G-banded karyotypes and screened EN1, GLI3, HAND2, HOXD13, ROR2, SALL1, SALL4, ZRS of SHH, SPRY4, TBX5, TWIST1 and WNT7A for point mutations using denaturing high performance liquid chromatography (DHPLC) and direct sequencing. Multiplex ligation dependent probe amplification (MLPA) kits were developed and used to measure copy number in GLI3, HOXD13, ROR2, SALL1, SALL4, TBX5 and the ZRS of SHH. RESULTS: Within the cohort, causative genetic alterations were identified in 23 patients (11%): mutations in GLI3 (n = 5), HOXD13 (n = 5), the ZRS of SHH (n = 4), and chromosome abnormalities (n = 4) were the most common lesions found. Clinical features that predicted the discovery of a genetic cause included a bilateral malformation, positive family history, and having increasing numbers of limbs affected (all p<0.01). Additionally, specific patterns of malformation predicted mutations in specific genes. CONCLUSIONS: Based on higher mutation prevalence the authors propose that GLI3, HOXD13 and the ZRS of SHH should be prioritised for introduction into molecular genetic testing programmes for CLM. The authors have developed simple criteria that can refine the selection of patients by surgeons for referral to clinical geneticists. The cohort also represents an excellent resource to test for mutations in novel candidate genes

Premature mortality attributable to smoking among Tunisian men in 2009

INTRODUCTION: Tobacco smoking is a significant public health threat in the world, a risk factor for many diseases, and has been increasing in prevalence in many developing countries. In this study, we aimed to estimate the burden of premature deaths attributable to smoking among Tunisian men aged 35-69 years in 2009. METHODS: The number of deaths attributable to smoking was estimated using the population attributable risk fraction method. Smoking prevalence was obtained from a nationally representative survey. Causes of death were obtained from the registry of the National Public Health Institute. Relative risks were taken from the American Cancer Society Prevention Study (CPS-II). RESULTS: Total estimated premature deaths attributable to smoking among men in Tunisia were 2601 (95% CI: 2268-2877), accounting for 25% (95% CI: 23.3-26.6) of total male adult mortality. Cancer, cardiovascular and respiratory diseases were the major causes of premature deaths attributable to smoking with 1272 (95% CI: 1188-1329), 966 (95% CI: 779-1133) and 364 (300-415) deaths, respectively. CONCLUSIONS: Tobacco smoking is highly relevant and is related to substantial premature mortality in Tunisia, around double that estimated for the region as a whole. This also has not decreased over the past 20 years. Urgent actions are needed to reduce this pandemic

Gauge Independent Trace Anomaly for Gravitons

We show that the trace anomaly for gravitons calculated using the usual effective action formalism depends on the choice of gauge when the background spacetime is not a solution of the classical equation of motion, that is, when off-shell. We then use the gauge independent Vilkovisky-DeWitt effective action to restore gauge independence to the off-shell case. Additionally we explicitly evaluate trace anomalies for some N-sphere background spacetimes.Comment: 19 pages, additional references and title chang

The Obliteration of Truth by Management: Badiou, St. Paul and the Question of Economic Managerialism in Education

This paper considers the questions that Badiou’s theory of the subject poses to cultures of economic managerialism within education. His argument that radical change is possible, for people and the situations they inhabit, provides a stark challenge to the stifling nature of much current educational climate. In 'Saint Paul: The Foundation of Universalism', Badiou describes the current universalism of capitalism, monetary homogeneity and the rule of the count. Badiou argues that the politics of identity are all too easily subsumed by the prerogatives of the marketplace and unable to present, therefore, a critique of the status quo. These processes are, he argues, without the potential for truth. What are the implications of Badiou’s claim that education is the arranging of ‘the forms of knowledge in such a way that truth may come to pierce a hole in them’ (Badiou, 2005, p. 9)? In this paper, I argue that Badiou’s theory opens up space for a kind of thinking about education that resists its colonisation by cultures of management and marketisation and leads educationalists to consider the emancipatory potential of education in a new light

A cross-sectional study of auditory verbal hallucinations experienced by people with a diagnosis of Borderline Personality Disorder

Background The presence of auditory verbal hallucinations (AVH) does not currently feature in the main diagnostic criteria for Borderline Personality Disorder (BPD). However, there is accumulating evidence that a high proportion of BPD patients report longstanding and frequent AVH which constitute a significant risk factor for suicide plans and attempts, and hospitalisation. Aim This study addressed questions about the validity and phenomenology of AVH in the context of BPD. The longer-term aim is to facilitate the development and translation of treatment approaches to address the unmet need of this population. Method This was a cross-sectional study, combining phenomenological and psychological assessments administered in person and online. We explored the experiences of 48 patients with a diagnosis of BPD who were hearing AVH. Results Participants gave ‘consistent’ reports on the measure of AVH phenomenology, suggesting that these experiences were legitimate. Similar to AVH in a psychosis context, AVH were experienced as distressing and appraised as persecutory. AVH were found to be weakly associated with BPD symptoms. AVH were also rated highly as a treatment priority by the majority of participants. Conclusion The findings suggest that AVH is a legitimate and distressing symptom of BPD and a treatment priority for some patients. The relative independence of AVH from other BPD symptoms and emotional states suggests that psychological treatment may need to be targeted specifically at the symptom of AVH. This treatment could be adapted from Cognitive Behaviour Therapy, the psychological intervention that is recommended for the treatment of AVH in the context of psychosis

Prokineticin-1 (PROK1) modulates interleukin (IL)-11 expression via prokineticin receptor 1 (PROKR1) and the calcineurin/NFAT signalling pathway

Prokineticin-1 (PROK1) is a multifunctional secreted protein which signals via the G-protein coupled receptor, PROKR1. Previous data from our laboratory using a human genome survey microarray showed that PROK1–prokineticin receptor 1 (PROKR1) signalling regulates numerous genes important for establishment of early pregnancy, including the cytokine interleukin (IL)-11. Here, we have shown that PROK1–PROKR1 induces the expression of IL-11 in PROKR1 Ishikawa cells and first trimester decidua via the calcium–calcineurin signalling pathway in a guanine nucleotide-binding protein (Gq/11), extracellular signal-regulated kinases, Ca2+ and calcineurin–nuclear factor of activated T cells dependent manner. Conversely, treatment of human decidua with a lentiviral miRNA to abolish endogenous PROK1 expression results in a significant reduction in IL-11 expression and secretion. Importantly, we have also shown a regulatory role for the regulator of calcineurin 1 isoform 4 (RCAN1-4). Overexpression of RCAN1-4 in PROKR1 Ishikawa cells using an adenovirus leads to a reduction in PROK1 induced IL-11 indicating that RCAN1-4 is a negative regulator in the calcineurin-mediated signalling to IL-11. Finally, we have shown the potential for both autocrine and paracrine signalling in the human endometrium by co-localizing IL-11, IL-11Rα and PROKR1 within the stromal and glandular epithelial cells of non-pregnant endometrium and first trimester decidua. Overall we have identified and characterized the signalling components of a novel PROK1–PROKR1 signalling pathway regulating IL-11

Inhomogeneous Field Configurations and the Electroweak Phase Transition

We investigate the effects of inhomogeneous scalar field configurations on the electroweak phase transition. For this purpose we calculate the leading perturbative correction to the wave function correction term Z(\vph,T), i.e., the kinetic term in the effective action, for the electroweak Standard Model at finite temperature and the top quark self--mass. Our finding for the fermionic contribution to Z(\vph,T) is infra--red finite and disagrees with other recent results. In general, neither the order of the phase transition nor the temperature at which it occurs change, once Z(\vph,T) is included. But a non--vanishing, positive (negative) Z(\vph,T) enhances (decreases) the critical droplet surface tension and the strength of the phase transition. We find that in the range of parameter space, which allows for a first--order phase transition, the wave function correction term is negative --- indicating a weaker phase transition --- and especially for small field values so large that perturbation theory becomes unreliable.Comment: 23 pages of LaTeX + 3 PostScript figures included in uuencoded form, FERMI-PUB-93/253-