Use of the Flixene vascular access graft as an early cannulation solution.

OBJECTIVE: The primary end points of this study were safety and efficacy of early cannulation of the Flixene graft (Maquet-Atrium Medical, Hudson, NH). Secondary end points were complications and patency. METHODS: This is a prospective single-center nonrandomized study. Study data included patient characteristics; history of vascular access; operative technique; interval between implantation and initial cannulation; complications; and patency at 1 month, 3 months, and every 6 months. Patency rates were estimated by the Kaplan-Meier method. RESULTS: Between January 2011 and September 2013, a total of 46 Flixene grafts were implanted in 44 patients (27 men) with a mean age of 63 years. The implantation site was the upper arm in 67% of cases, the forearm in 11%, and the thigh in 22%. Seven grafts were never cannulated during the study period. Of the remaining 39 grafts, 32 (82%) were successfully cannulated within the first week after implantation, including 16 (41%) on the first day. The median interval from implantation to initial cannulation was 2 days (interquartile range, 1-3 days). The median follow-up was 223.5 days (interquartile range, 97-600 days). Five hematomas occurred, but only one required surgical revision. Primary assisted and secondary patency rates were 65% and 86%, respectively, at 6 months and 56% and 86%, respectively, at 1 year. CONCLUSIONS: This study suggests that cannulation of the Flixene graft within 1 week after implantation is safe and effective. Early cannulation avoids or shortens the need for a temporary catheter. One-year patency rates appeared to be comparable to those achieved with conventional grafts, but long-term follow-up and randomized controlled studies will be needed to confirm this finding.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial.

BACKGROUND: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments. METHODS: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures. RESULTS: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons. CONCLUSIONS: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Overexpression of GPC6 and TMEM132D in Early Stage Ovarian Cancer Correlates with CD8+ T-Lymphocyte Infiltration and Increased Patient Survival.

Infiltration of cytotoxic T-lymphocytes in ovarian cancer is a favorable prognostic factor. Employing a differential expression approach, we have recently identified a number of genes associated with CD8+ T-cell infiltration in early stage ovarian tumors. In the present study, we validated by qPCR the expression of two genes encoding the transmembrane proteins GPC6 and TMEM132D in a cohort of early stage ovarian cancer patients. The expression of both genes correlated positively with the mRNA levels of CD8A, a marker of T-lymphocyte infiltration [Pearson coefficient: 0.427 (p = 0.0067) and 0.861 (p < 0.0001), resp.]. GPC6 and TMEM132D expression was also documented in a variety of ovarian cancer cell lines. Importantly, Kaplan-Meier survival analysis revealed that high mRNA levels of GPC6 and/or TMEM132D correlated significantly with increased overall survival of early stage ovarian cancer patients (p = 0.032). Thus, GPC6 and TMEM132D may serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis, prognosis, and tumor immunobattling.

Biopolttoaineiden käyttö mikroturbiineissa

Työssä tutkittiin suoran ja epäsuoran mikroturbiiniprosessin toimintaa. Lisäksi työssä on kerrottu tarvittavista biopolttoaineista, apulaitteista sekä suurnopeustekniikasta.

Sähkön tuotantokustannusvertailu

Työssä vertaillaan eri sähköntuotantovaihtoehtojen taloudellista kannattavuutta. Kannattavuusvertailu suoritetaan pelkkää sähköä tuottaville voimalaitoksille. Sähkön ja lämmön yhteistuotannon lisärakentaminen tulee kattamaan tietyn osuuden lähitulevaisuuden sähkön hankinnan vajeesta, mutta sen lisäksi tarvitaan myös uutta lauhdetuotantokapasiteettia. Tutkittavat voimalaitostyypit ovat: ydinvoimalaitos, maakaasukombilauhdevoimalaitos, kivihiililauhdevoimalaitos, turvelauhdevoimalaitos, puulauhdevoimalaitos ja tuulivoimala. Kannattavuustarkastelu suoritetaan annuiteettimenetelmällä käyttäen 5 % reaalikorkoa ja tammikuun 2008 hintatasoa. Laskelmien perusteella 8000 tunnin huipunkäyttöajalla ydinsähkön tuotantokustannus olisi 35,0 € /MWh, kaasusähkön 59,2 €/MWh ja hiilisähkön 64,4 €/MWh, kun hiilidioksidipäästöoikeuden hintana käytetään 23 €/t. Ilman päästökauppaa kaasusähkön hinta on 51,2 €/MWh ja hiilisähkön 45,7 €/MWh ydinsähkön hinnan pysyessä ennallaan. Herkkyystarkastelun tulosten perusteella ydinvoiman kilpailukyky korostuu muihin tarkasteltuihin tuotantomuotoihin verrattuna. Ydinpolttoaineen suurellakaan hinnan muutoksella ei ole merkittävää vaikutusta ydinsähkön tuotantokustannukseen, kun taas maakaasusähkö on erittäin riippuvainen polttoaineen hinnasta. Myös päästöoikeuden hinnan kasvu lisää merkittävästi ydinvoiman kilpailukykyä kaasu- ja hiilisähköön verrattuna. Ydinvoimainvestoinnin kannattavuutta ja takaisinmaksua tarkastellaan myös yksinään siten, että investoinnilla saavutettavien tuottojen laskennassa käytetään useita eri sähkön markkinahintoja. Investoinnin kannattavuus on erittäin hyvä, kun sähkön markkinahinta on 50 €/MWh tai suurempi.

Les bifurcations du récit interactif: continuité ou rupture?

Ainsi que l'affirmaient les premiers narratologues, le récit est une forme qui transcende les médias et si l'on peut reconnaître ses « avatars » jusque dans les jeux de rôle et les jeux vidéo, alors la confrontation entre narratologie et ludologie peut s'avérer une étape incontournable dans la refondation des concepts de la théorie du récit. Ainsi que l'affirmait récemment Werner Wolf : « une approche intermédiale peut [...] contribuer à éviter les généralisations unilatérales que l'on a pu observer dans les recherches mono-médiales antérieures » en particulier dans les travaux « centrés sur les textes verbaux » (Wolf 2003 : 193, n.t.). En retour, on peut espérer que ce recadrage conceptuel offre un point de vue nouveau sur les phénomènes narratifs, dont l'impact pourrait aller jusqu'à transformer notre appréhension des romans de l'âge baroque jusqu'aux fictions télévisuelles qui dominent le paysage médiatique contemporain. Ce numéro des Cahiers de narratologie est issu d'une journée d'étude qui s'est tenue à l'Université de Lausanne (UNIL) le 14 février 2014. Cette journée était organisée par Raphaël Baroni, Marc Marti, Claire Clivaz et Frédéric Kaplan et elle a bénéficié du soutien de l'EFLE (UNIL), du LADHUL (UNIL), du LIRCES (Université de Nice Sophia Antipolis), du DHLAB (Ecole Polytechnique Fédérale de Lausanne) et du Réseau romand de narratologie.

Comparison of electricity generation costs

The economical competitiveness of various power plant alternatives is compared. The comparison comprises merely electricity producing power plants. Combined heat and power (CHP) producing power will cover part of the future power deficit in Finland, but also condensing power plants for base load production will be needed. The following types of power plants are studied: nuclear power plant, combined cycle gas turbine plant, coal-fired condensing power plant, peat-fired condensing power plant, wood-fired condensing power plant and wind power plant. The calculations are carried out by using the annuity method with a real interest rate of 5 % per annum and with a fixed price level as of January 2008. With the annual peak load utilization time of 8000 hours (corresponding to a load factor of 91,3 %) the production costs would be for nuclear electricity 35,0 €/MWh, for gas based electricity 59,2 €/MWh and for coal based electricity 64,4 €/MWh, when using a price of 23 €/tonCO2 for the carbon dioxide emission trading. Without emission trading the production cost of gas electricity is 51,2 €/MWh and that of coal electricity 45,7 €/MWh and nuclear remains the same (35,0 €/MWh) In order to study the impact of changes in the input data, a sensitivity analysis has been carried out. It reveals that the advantage of the nuclear power is quite clear. E.g. the nuclear electricity is rather insensitive to the changes of nuclear fuel price, whereas for natural gas alternative the rising trend of gas price causes the greatest risk. Furthermore, increase of emission trading price improves the competitiveness of the nuclear alternative. The competitiveness and payback of the nuclear power investment is studied also as such by using various electricity market prices for determining the revenues generated by the investment. The profitability of the investment is excellent, if the market price of electricity is 50 €/MWh or more.

Incidence of outer retinal tubulation in ranibizumab-treated age-related macular degeneration.

PURPOSE: To investigate the incidence of outer retinal tubulation (ORT) in ranibizumab-treated neovascular age-related macular degeneration patients. METHODS: We included 480 consecutive patients (546 eyes) with neovascular age-related macular degeneration, who were treated with variable-dosing intravitreal ranibizumab, evaluated with spectral domain optical coherence tomography, and followed-up for a minimum period of 6 months. Optical coherence tomographies were evaluated for the first appearance of ORT, precursor signs, and type of underlying lesion. Visual acuity was also recorded. RESULTS: Outer retinal tubulation was observed in 30% of eyes during a mean follow-up period of 26.7 months (SD, 13.5). Kaplan-Meier survival analysis revealed that the ORT incidence (2.5, 17.5, 28.4, and 41.6% at baseline, after 1, 2, and 4 years, respectively) continuously increased, despite visually effective anti-vascular endothelial growth factor treatment. Outer retinal tubulation was associated with a poorer functional benefit. Lower baseline visual acuity was associated with a higher risk of developing ORT. CONCLUSION: Incidence of ORT continuously increases despite visually optimal anti-vascular endothelial growth factor treatment of age-related macular degeneration. Outer retinal tubulation might be considered a prognostic factor for functional outcome and is relevant to avoid overtreatment.

Impaired aldehyde dehydrogenase 1 subfamily member 2A-dependent retinoic acid signaling is related with a mesenchymal-like phenotype and an unfavorable prognosis of head and neck squamous cell carcinoma.

BACKGROUND: An inverse correlation between expression of the aldehyde dehydrogenase 1 subfamily A2 (ALDH1A2) and gene promoter methylation has been identified as a common feature of oropharyngeal squamous cell carcinoma (OPSCC). Moreover, low ALDH1A2 expression was associated with an unfavorable prognosis of OPSCC patients, however the causal link between reduced ALDH1A2 function and treatment failure has not been addressed so far. METHODS: Serial sections from tissue microarrays of patients with primary OPSCC (n = 101) were stained by immunohistochemistry for key regulators of retinoic acid (RA) signaling, including ALDH1A2. Survival with respect to these regulators was investigated by univariate Kaplan-Meier analysis and multivariate Cox regression proportional hazard models. The impact of ALDH1A2-RAR signaling on tumor-relevant processes was addressed in established tumor cell lines and in an orthotopic mouse xenograft model. RESULTS: Immunohistochemical analysis showed an improved prognosis of ALDH1A2(high) OPSCC only in the presence of CRABP2, an intracellular RA transporter. Moreover, an ALDH1A2(high)CRABP2(high) staining pattern served as an independent predictor for progression-free (HR: 0.395, p = 0.007) and overall survival (HR: 0.303, p = 0.002), suggesting a critical impact of RA metabolism and signaling on clinical outcome. Functionally, ALDH1A2 expression and activity in tumor cell lines were related to RA levels. While administration of retinoids inhibited clonogenic growth and proliferation, the pharmacological inhibition of ALDH1A2-RAR signaling resulted in loss of cell-cell adhesion and a mesenchymal-like phenotype. Xenograft tumors derived from FaDu cells with stable silencing of ALDH1A2 and primary tumors from OPSCC patients with low ALDH1A2 expression exhibited a mesenchymal-like phenotype characterized by vimentin expression. CONCLUSIONS: This study has unraveled a critical role of ALDH1A2-RAR signaling in the pathogenesis of head and neck cancer and our data implicate that patients with ALDH1A2(low) tumors might benefit from adjuvant treatment with retinoids.

New-onset refractory status epilepticus: Etiology, clinical features, and outcome.

OBJECTIVES: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. METHODS: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). RESULTS: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. CONCLUSIONS: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

EEG as an Indicator of Cerebral Functioning in Postanoxic Coma.

Postanoxic coma after cardiac arrest is one of the most serious acute cerebral conditions and a frequent cause of admission to critical care units. Given substantial improvement of outcome over the recent years, a reliable and timely assessment of clinical evolution and prognosis is essential in this context, but may be challenging. In addition to the classic neurologic examination, EEG is increasingly emerging as an important tool to assess cerebral functions noninvasively. Although targeted temperature management and related sedation may delay clinical assessment, EEG provides accurate prognostic information in the early phase of coma. Here, the most frequently encountered EEG patterns in postanoxic coma are summarized and their relations with outcome prediction are discussed. This article also addresses the influence of targeted temperature management on brain signals and the implication of the evolution of EEG patterns over time. Finally, the article ends with a view of the future prospects for EEG in postanoxic management and prognostication.

Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial.

BACKGROUND: Postoperative hemithoracic radiotherapy has been used to treat malignant pleural mesothelioma, but it has not been assessed in a randomised trial. We assessed high-dose hemithoracic radiotherapy after neoadjuvant chemotherapy and extrapleural pneumonectomy in patients with malignant pleural mesothelioma. METHODS: We did this phase 2 trial in two parts at 14 hospitals in Switzerland, Belgium, and Germany. We enrolled patients with pathologically confirmed malignant pleural mesothelioma; resectable TNM stages T1-3 N0-2, M0; WHO performance status 0-1; age 18-70 years. In part 1, patients were given three cycles of neoadjuvant chemotherapy (cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 given every 3 weeks) and extrapleural pneumonectomy; the primary endpoint was complete macroscopic resection (R0-1). In part 2, participants with complete macroscopic resection were randomly assigned (1:1) to receive high-dose radiotherapy or not. The target volume for radiotherapy encompassed the entire hemithorax, the thoracotomy channel, and mediastinal nodal stations if affected by the disease or violated surgically. A boost was given to areas at high risk for locoregional relapse. The allocation was stratified by centre, histology (sarcomatoid vs epithelioid or mixed), mediastinal lymph node involvement (N0-1 vs N2), and T stage (T1-2 vs T3). The primary endpoint of part 1 was the proportion of patients achieving complete macroscopic resection (R0 and R1). The primary endpoint in part 2 was locoregional relapse-free survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00334594. FINDINGS: We enrolled patients between Dec 7, 2005, and Oct 17, 2012. Overall, we analysed 151 patients receiving neoadjuvant chemotherapy, of whom 113 (75%) had extrapleural pneumonectomy. Median follow-up was 54·2 months (IQR 32-66). 52 (34%) of 151 patients achieved an objective response. The most common grade 3 or 4 toxic effects were neutropenia (21 [14%] of 151 patients), anaemia (11 [7%]), and nausea or vomiting (eight [5%]). 113 patients had extrapleural pneumonectomy, with complete macroscopic resection achieved in 96 (64%) of 151 patients. We enrolled 54 patients in part 2; 27 in each group. The main reasons for exclusion were patient refusal (n=20) and ineligibility (n=10). 25 of 27 patients completed radiotherapy. Median total radiotherapy dose was 55·9 Gy (IQR 46·8-56·0). Median locoregional relapse-free survival from surgery, was 7·6 months (95% CI 4·5-10·7) in the no radiotherapy group and 9·4 months (6·5-11·9) in the radiotherapy group. The most common grade 3 or higher toxic effects related to radiotherapy were nausea or vomiting (three [11%] of 27 patients), oesophagitis (two [7%]), and pneumonitis (two [7%]). One patient died of pneumonitis. We recorded no toxic effects data for the control group. INTERPRETATION: Our findings do not support the routine use of hemithoracic radiotherapy for malignant pleural mesothelioma after neoadjuvant chemotherapy and extrapleural pneumonectomy. FUNDING: Swiss Group for Clinical Cancer Research, Swiss State Secretariat for Education, Research and Innovation, Eli Lilly.

High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.

PURPOSE: To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients. DESIGN: Retrospective clinical and molecular genetic study. METHODS: Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot. RESULTS: We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families. CONCLUSIONS: The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed.

Vestibular Schwannoma: The Evolution of Hearing and Tumor Size in Natural Course and after Treatment by LINAC Stereotactic Radiosurgery.

OBJECTIVE: To review the natural course of tumor size and hearing during conservative management of 151 patients with unilateral vestibular schwannoma (VS), and to evaluate the same parameters for the part of the group (n = 84) who were treated by LINAC stereotactic radiosurgery (SRS). METHODS: In prospectively collected data, patients underwent MRI and complete audiovestibular tests at inclusion, during the conservative management period and after SRS. Hearing was graded according to the Gardner-Robertson (GR) scale and tumor size according to Koos. Statistics were performed using Kaplan-Meier survival analysis and multivariate analyses including linear and logistic regression. Specific insight was given to patients with serviceable hearing. RESULTS: During the conservative management period (mean follow-up time: 24 months, range: 6-96), the annual risk of GR class degradation was 6% for GRI and 15% for GR II patients. Hearing loss as an initial symptom was highly predictive of further hearing loss (p = 0.003). Tumor growth reached 25%. For SRS patients, functional hearing preservation was 51% at 1 year and 36% at 3 years. Tumor control was 94 and 91%, respectively. CONCLUSION: In VS patients, hearing loss at the time of diagnosis is a predictor of poorer hearing outcome. LINAC SRS is efficient for tumor control. Patients who preserved their pretreatment hearing presented less hearing loss per year after SRS than before treatment, suggesting a protective effect of SRS when cochlear function can be preserved.