Pregnancy Following Failed Sterilisation Under the Accident Compensation Scheme

This paper analyses the approach that is taken in New Zealand in determining coverage for pregnancies following failed sterilisations under the accident compensation scheme. The approach adopted in the recent decision of the Court of Appeal in ACC v D is criticised and an alternative approach for determining whether such claims ought to be within the accident compensation scheme is suggested

Systemic Escherichia coli infection does not influence clinical symptoms and neurodegeneration in experimental autoimmune encephalomyelitis

BACKGROUND: Systemic infections can influence the course of multiple sclerosis (MS), especially by driving recurrent acute episodes. The question whether the infection enhances tissue damage is of great clinical importance and cannot easily be assessed in clinical trials. Here, we investigated the effects of a systemic infection with Escherichia coli, a Gram-negative bacterium frequently causing urinary tract infections, on the clinical course as well as on neurodegeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODS: Rats were immunized with myelin oligodendrocyte glycoprotein (MOG(1–125)) and challenged intraperitoneally with live E. coli K1 in the preclinical or in the clinical phase of the disease. To ensure the survival of animals, antibiotic treatment with ceftriaxone was initiated 36 h after the infection and continued for 3 consecutive days. RESULTS: Systemic infection with E. coli did not influence the onset of clinical EAE symptoms or disease severity. Analysis of the optic nerve and retinal ganglion cells revealed no significant changes in the extent of inflammatory infiltrates, demyelination and neurodegeneration after E. coli infection. CONCLUSIONS: We could not confirm the detrimental effect of lipopolysaccharide-induced systemic inflammation, a model frequently used to mimic the bacterial infection, previously observed in animal models of MS. Our results indicate that the effect of an acute E. coli infection on the course of MS is less pronounced than suspected and underline the need for adequate models to test the role of systemic infections in the pathogenesis of MS

Distribution of p63, a novel myoepithelial marker, in fine-needle aspiration biopsies of the breast: an analysis of 82 samples

BACKGROUND. The presence of myoepithelial cells (MECs) in fine-needle aspiration biopsies (FNAB) of the breast constitute an important criterion used to diagnose benign breast lesions. However, MECs sometimes have a distorted cytomorphology, and most of the previously evaluated myoepithelial markers do not have satisfactory sensitivity and specificity. p63, a recently characterized p53 homolog, is a nuclear transcription factor that is expressed in basal cells of multilayered epithelia and myoepithelial cells of the breast. The authors analyzed the immunocytochemical distribution of p63 in a series of 82 breast FNABs (30 benign lesions and 52 malignant breast lesions). METHODS. Eighty-two archival, Papanicolaou-stained smears of breast lesions were retrieved from the files of the authors’ institutions. Immunocytochemistry was performed according to the streptavidin-biotin-peroxidase complex technique using the antibody 4A4 (against all p63 isoforms). Two pathologists evaluated the distribution of p63 positive cells. Only nuclear reactivity was considered specific. RESULTS. In benign lesions, p63 decorated the nuclei of MECs in all samples. p63 also stained naked nuclei in fibroadenomas. In malignant lesions, p63 was positive in MECs overlying malignant cell clusters in all 8 samples of ductal carcinoma in situ (DCIS), in 9 of 16 samples of pure invasive carcinomas (IC), and in 16 of 20 samples that contained both DCIS and IC. In 18 samples (36%), a variable population of p63 positive, malignant cells was observed. p63 failed to decorate stromal, neural, adipocytic, and smooth muscle cells in all samples. CONCLUSIONS. p63 is a reliable nuclear marker of MECs in breast aspirates. Regardless of the fact that variable proportions of p63 positive, malignant cells were observed in 36% of breast carcinoma aspirates, p63 may be a useful adjunct antibody to confirm the presence of MECs in FNABs of benign breast lesions.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/5386/2001

APPRENDRE ET ENSEIGNER AVEC LA BIENVEILLANCE : POUR UNE NOUVELLE PEDAGOGIE FRANÇAISE

This thesis focuses on reflections made my contemporary thinkers in France concerning the wellness of children through their times in French public schools. Journalists, educators, parents seem to agree that the current French pedagogy instilled in the Education nationale system can no longer be acceptable and needs profound change. If academic performances are important, they cannot be the only center of interest in French schools. Instead, these writers propose and advocate for a pedagogy where wellness, benevolence and personal happiness occupy a crucial place. The purpose of this thesis is to identify these voices and to take into account the fact that the world of education is discussed, questioned beyond the walls of education. The pédagogie de la bienveillance, or benevolence pedagogy, transcends one particular field. Instead, people concerned about children’s emotional health advocate for a change in order to help these children become happy adults. Instead of just denouncing a system that they deem unjust, each of the writers presented in this thesis, offer alternatives, solutions. They also document experiments they have conducted and offer their experience as possibilities to teach differently and to consider children differently as well

Study of gas-liquid mixing in stirred vessel using electrical resistance tomography

This study presents a full operation and optimisation of a mixing unit; an innovative approach is developed to address the behaviour of gas-liquid mixing by using Electrical Resistance Tomography (ERT). The validity of the method is investigated by developing the tomographic images using different numbers of baffles in a mixing unit. This technique provided clear visual evidence of better mixing that took place inside the gasliquid system and the effect of a different number of baffles on mixing characteristics. For optimum gas flow rate (m3/s) and power input (kW), the oxygen absorption rate in water was measured. Dynamic gassingout method was applied for five different gas flow rates and four different power inputs to find out mass transfer coefficient (KLa). The rest of the experiments with one up to four baffles were carried out at these optimum values of power input (2.0 kW) and gas flow rate (8.5×10-4 m3/s). The experimental results and tomography visualisations showed that the gasliquid mixing with standard baffling provided near the optimal process performance and good mechanical stability, as higher mass transfer rates were obtained using a greater number of baffles. The addition of single baffle had a striking effect on mixing efficiency and additions of further baffles significantly decrease mixing time. The energy required for complete mixing was remarkably reduced in the case of four baffles as compared to without any baffle. The process economics study showed that the increased cost of baffles installation accounts for less cost of energy input for agitation. The process economics have also revealed that the optimum numbers of baffles are four in the present mixing unit and the use of an optimum number of baffles reduced the energy input cost by 54%

Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas-an ENITEC Group Initiative

Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. Experimental Design: We investigated the expression of several druggable targets (phospho-S6(S240) ribosomal protein, PTEN, PDGFR-alpha, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6(S240), was tested in patient-derived xenograft (PDX) leiomyosarcoma models. Results: In uterine sarcomas and STUMPs, S6S240 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade (P = 0.001) and recurrence (P = 0.019), as shown by logistic regression. In addition, p-S6(S240) correlated with shorter progression-free survival (P = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6(S240) expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6(S240) in response prediction to PI3K/mTOR inhibition. Conclusions: Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6(S240) expression is a potential predictive biomarker for response to treatment. (C)2017 AACR.Peer reviewe

Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC) inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat) on MES-SA uterine sarcoma cells <it>in vitro </it>and <it>in vivo</it>. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21^WAF1and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma <it>in vivo</it>.</p> <p>Results</p> <p>Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM) already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3) as well as class II (HDAC7) were preferentially affected by this treatment. Vorinostat significantly increased p21^WAF1expression and apoptosis. Nude mice injected with 5 × 10⁶MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day) and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice.</p> <p>Conclusions</p> <p>Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.</p