Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals.

Clin Microbiol Infect 2011; 17: 1366-1371 ABSTRACT: Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

A comparative study of T-cell receptor V beta usage in non-obese diabetic (NOD) and I-E transgenic NOD mice.

The non-obese diabetic (NOD) mouse is a model for the study of insulin-dependent diabetes mellitus (IDDM). Recently transgenic NOD mice have been derived (NOD-E) that express the major histocompatibility complex (MHC) class II I-E molecule. NOD-E do not become diabetic and show negligible pancreatic insulitis. The possibility pertained that NOD-E mice are protected from disease by a process of T-cell deletion or anergy. This paper describes our attempts to discover whether this was so, by comparing NOD and NOD-E mouse T-cell receptor V beta usage. Splenocytes and lymph node cells were therefore tested for their ability to proliferate in response to monoclonal anti-V beta antibodies. We were unable to show any consistent differences between NOD and NOD-E responses to the panel of antibodies used. Previously proposed V beta were shown to be unlikely candidates for deletion or anergy. T cells present at low frequency (V beta 5+) in both NOD and NOD-E mice were shown to be as capable of expansion in response to antigenic stimulation as were more frequently expressed V beta. Our data therefore do not support deletion or anergy as mechanisms which could account for the observed disease protection in NOD-E mice.

Age over 40 years increases the failure rate of non-operative management of blunt splenic injuries

Objective: Non-operative management (NOM) of blunt splenic injuries (BSI) is nowadays considered the standard treatment. The study aimed to determine the criteria applied for NOM and to identify risk factors for its failure. Methods: Review of all adult patients with BSI treated at the University Hospital Bern, Switzerland, between 2000 and 2008. Results: There were 206 patients (146 men, 70·9%) with a mean age of 38·2 ± 19·1 years and an Injury Severity Score of 30·9 ± 11·6. The American Association for the Surgery of Trauma classification of the splenic injury was: grade I, n=43 (20·9%); grade II, n=52 (25·2%); grade III, n=60 (29·1%); grade IV, n=42 (20·4%) and grade V, n=9 (4·4%). 47 patients (22·8%) required immediate surgery. Five or more units of red cell transfusions (P<0·001), Glasgow Coma Scale<11 (P=0·009) and age ≥55 years (P=0·038) were associated with primary operative management (OM). 159 patients (77·2%) qualified for NOM, which was successful in 89·9% (143/159). The overall splenic salvage rate was 69·4% (143/206). Multivariate analysis found age ≥40 years to be the only factor independently related to the failure of NOM (P=0·001). Conclusion: Advanced age is associated with an increased failure rate ofNOM in patients with BSI.

Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts.

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.

Arrest du Conseil d'Etat du Roy. Du 12 octobre 1700. Concernant les sucres bruts & non raffinez, provenants de l'isle de Cayenne, qui seront déchargez à Nantes & voiturez sans séjour à droiture par le bureau d'Ingrande...

[Acte. 1700-10-12. Fontainebleau]

8-month non-use of a language. A case tudy. A longitudinal study of the effects on non use of one of the languages (Spanish) of a German L1 multilingual

Under the Dynamic Model of Multilingualism multilinguals are especially vulnerable to language attrition. It was the aim of the present study to verify if this was the case and to observe whether the different linguistic skills (receptive vs. descriptive) and the different linguistic levels (syntactic, lexical, morphological, etc.) would be affected equally.Data were gathered longitudinally by means of a language test for the subject’s reading, writing, listening and speaking skills as well as her knowledge of grammar and vocabulary. Although the overall accuracy remained intact and no proof for attrition in the receptive skills was found, the productive skills - mainly fluency - were shown to have suffered from language attrition. This was demonstrated by an increase in the number of pauses, hesitations, repetitions and self-corrections among others and decrease in the percentage of error-free clauses and decrease in the clause length, in oral and written fluency respectively.

Wörter stehen da einige. On nominal split topicalization in non-standard viennese german

This work investigates the syntactic, semantic, and pragmatic properties of nominal Split Topicalization (ST) constructions in Standard and non-Standard German. The topic phrase denotes a property, and the MF phrase either modifies this property or picks out a specific entity. Semantically, the topic phrase will be analysed as a property-denoting expression which restricts the denotation of the verbal predicate, while the MF phrase is composed either via specify or restrict (cf. Chung and Ladusaw, 2003). Syntactically, the base position of the topic phrase is the (incorporating) verb, and the MF phrase is generated independently as the complement of the verb containing an empty pronoun. Since predicates introduce abstract discourse referents, the topic phrase can be resumed via "pro" in the MF phrase.

A non-interventional phase IV Belgian survey to assess the antiviral effectiveness of pegylated interferon-alpha-2b and ribavirin treatment according to the stage of liver fibrosis in previously untreated patients with genotype 1/4/5/6 chronic hepatitis C (PRACTICE).

BACKGROUND AND STUDY AIMS: This was an observational, non-interventional, multicenter, phase IV study, in patients with genotype 1/4/5/6 chronic hepatitis C (CHC). The primary objectives were to evaluate SVR in patients with no or minimal fibrosis (METAVIR F0-F1) versus well established fibrosis (F2-F4), and to estimate response on Weeks 12, 24 and 48 on treatment in previously untreated patients with genotypes 1/4/5/6 CHC. PATIENTS AND METHODS: 538 patients treated with pegylated interferon alfa 2b 1.5 mcg/kg in combination with ribavirin 800-1200 mg/day were enrolled in 55 sites in Belgium and Luxembourg, 505 being considered for the analysis. 40% of the patients were female and 60% male, the average age was 47.5 years, 10.5% were 65 or older. RESULTS: SVR was observed in 35% of the patients, EVR in 68%, of which pEVR in 33% and cEVR in 35%. SVR was observed in 43% of the low fibrosis group (F0, F1) and 30% of the high fibrosis group (F2, F3, F4) (p = 0.005). SVR rates were 34% for genotype 1, 37% for genotype 4, and 47% for genotype 5 (NS). Multivariate analysis showed that EVR and baseline METAVIR score are independent prognostic factors for SVR. CONCLUSIONS: This trial confirms that fibrosis stage and early viral response are the most important key-factors to predict sustained response, suggesting that the earlier patients are treated, the better the outcome. Non-invasive techniques enable us to closely monitor progression of fibrosis, allowing a better selection of patients for antiviral treatment in the DAA-era.

Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells.

BACKGROUND: Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian. RESULTS: We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types. CONCLUSIONS: The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.

Non-Quasi-Competitiveness and Stability in Cournot's Model

This paper retakes previous work of the authors, about the relationship between non-quasi-competitiveness (the increase in price caused by an increase in the number of oligopolists) and stability of the equilibrium in the classical Cournot oligopoly model. Though it has been widely accepted in the literature that the loss of quasi-competitiveness is linked, in the long run as new firms entered the market, to instability of the model, the authors in their previous work put forward a model in which a situation of monopoly changed to duopoly losing quasi-competitiveness but maintaining the stability of the equilibrium. That model could not, at the time, be extended to any number of oligopolists. The present paper exhibits such an extension. An oligopoly model is shown in which the loss of quasi-competitiveness resists the presence in the market of as many firms as one wishes and where the successive Cournot's equilibrium points are unique and asymptotically stable. In this way, for the first time, the conjecture that non-quasi- competitiveness and instability were equivalent in the long run, is proved false.

Cerebral extracellular lactate increase is predominantly non ischemic in patients with severe traumatic brain injury

Le cerveau est l'organe avec les besoins en énergie les plus élevés du corps humain, et le glucose est un substrat énergétique cérébral essentiel. Ces dernières décennies, la compréhension de la neuroénergétique a beaucoup évolué et un rôle du lactate comme substrat énergétique important a été mis en évidence, notamment suite à l'introduction du modèle de l'ANLS (astrocyte-neuron lactate shuttle). Selon celui-ci, les astrocytes convertissent le glucose en lactate par réaction de glycolyse, puis il est transporté jusqu'aux neurones qui l'utilisent comme source d'énergie à travers le cycle de Krebs. Chez l'homme, divers travaux récents ont montré que le lactate peut servir de « carburant » cérébral chez le sujet sain, après effort intense ou chez le patient diabétique. La régulation métabolique et le rôle du lactate après lésion cérébrale aiguë sont encore peu connus. Présentation de l'article Le but de ce travail a été d'étudier le métabolisme cérébral du lactate chez les patients atteints de traumatisme crânien (TCC) sévère. Nous avons émis l'hypothèse que l'augmentation du lactate cérébral chez ces patients n'était pas associée de manière prédominante à une hypoxie ou une ischémie mais plutôt à une glycolyse aérobie, et également à une perfusion cérébrale normale. L'étude a porté sur une cohorte prospective de 24 patients avec TCC sévère admis au service de médecine intensive du CHUV (centre hospitalier universitaire vaudois), monitorés par un système combinant microdialyse cérébrale (outil permettant de mesurer divers métabolites cérébraux, tels que le lactate, le pyruvate et le glucose), mesure de la pression cérébrale en oxygène et de la pression intracrânienne. Cet outil nous a permis de déterminer si l'élévation du lactate était principalement associée à une glycolyse active ou plutôt à une hypoxie. L'utilisation du CTde perfusion a permis d'évaluer la relation entre les deux patterns d'élévation du lactate (glycolytique ou hypoxique) et la perfusion cérébrale globale. Nos résultats ont montré que l'augmentation du lactate cérébral chez les patients avec TCC sévère était associée de manière prédominante à une glycolyse aérobie plutôt qu'à une hypoxie/ischémie. D'autre part, nous avons pu confirmer que les épisodes de lactate glycolytique étaient toujours associés à une perfusion cérébrale normale ou augmentée, alors que les épisodes de lactate hypoxique étaient associés à une hypoperfusion cérébrale. Conclusions et perspectives Nos résultats, qui ont permis de mieux comprendre le métabolisme cérébral du lactate chez les patients avec TCC sévère, soutiennent le concept que le lactate est produit dans des conditions aérobes et pourrait donc être utilisé comme source d'énergie par le cerveau lésé pour subvenir à des besoins augmentas. Etant donné que la dysfonction énergétique est une des probables causes de perte neuronale après traumatisme crânien, ces résultats ouvrent des perspectives thérapeutiques nouvelles après agression cérébrale chez l'homme, visant à tester un potentiel effet neuroprotecteur via l'administration de lactate exogène.