Negative Effect of Smoking on the Performance of the QuantiFERON TB Gold in Tube Test.

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively. Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results. Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02). Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status

Cardiac ultrasound in resource-limited settings (CURLS): towards a wider use of basic echo applications in Africa

Background: Point-of-care ultrasound is increasingly being used as a diagnostic tool in resource-limited settings. The majority of existing ultrasound protocols have been developed and implemented in high-resource settings. In sub-Saharan Africa (SSA), patients with heart failure of various etiologies commonly present late in the disease process, with a similar syndrome of dyspnea, edema and cardiomegaly on chest X-ray. The causes of heart failure in SSA differ from those in high-resource settings. Point-of-care ultrasound has the potential to identify the underlying etiology of heart failure, and lead to targeted therapy. Based on a literature review and weighted score of disease prevalence, diagnostic impact and difficulty in performing the ultrasound, we propose a context-specific cardiac ultrasound protocol to help differentiate patients presenting with heart failure in SSA. Results: Pericardial effusion, dilated cardiomyopathy, cor pulmonale, mitral valve disease, and left ventricular hypertrophy were identified as target conditions for a focused ultrasound protocol in patients with cardiac failure and cardiomegaly in SSA. By utilizing a simplified 5-question approach with all images obtained from the subxiphoid view, the protocol is suitable for use by health care professionals with limited ultrasound experience. Conclusions: The “Cardiac ultrasound for resource-limited settings (CURLS)” protocol is a context-specific algorithm designed to aid the clinician in diagnosing the five most clinically relevant etiologies of heart failure and cardiomegaly in SSA. The protocol has the potential to influence treatment decisi

The Compartmentalisation of Phosphorylated Free Oligosaccharides in Cells from a CDG Ig Patient Reveals a Novel ER-to-Cytosol Translocation Process

BACKGROUND: Biosynthesis of the dolichol linked oligosaccharide (DLO) required for protein N-glycosylation starts on the cytoplasmic face of the ER to give Man(5)GlcNAc(2)-PP-dolichol, which then flips into the ER for further glycosylation yielding mature DLO (Glc(3)Man(9)GlcNAc(2)-PP-dolichol). After transfer of Glc(3)Man(9)GlcNAc(2) onto protein, dolichol-PP is recycled to dolichol-P and reused for DLO biosynthesis. Because de novo dolichol synthesis is slow, dolichol recycling is rate limiting for protein glycosylation. Immature DLO intermediates may also be recycled by pyrophosphatase-mediated cleavage to yield dolichol-P and phosphorylated oligosaccharides (fOSGN2-P). Here, we examine fOSGN2-P generation in cells from patients with type I Congenital Disorders of Glycosylation (CDG I) in which defects in the dolichol cycle cause accumulation of immature DLO intermediates and protein hypoglycosylation. METHODS AND PRINCIPAL FINDINGS: In EBV-transformed lymphoblastoid cells from CDG I patients and normal subjects a correlation exists between the quantities of metabolically radiolabeled fOSGN2-P and truncated DLO intermediates only when these two classes of compounds possess 7 or less hexose residues. Larger fOSGN2-P were difficult to detect despite an abundance of more fully mannosylated and glucosylated DLO. When CDG Ig cells, which accumulate Man(7)GlcNAc(2)-PP-dolichol, are permeabilised so that vesicular transport and protein synthesis are abolished, the DLO pool required for Man(7)GlcNAc(2)-P generation could be depleted by adding exogenous glycosylation acceptor peptide. Under conditions where a glycotripeptide and neutral free oligosaccharides remain predominantly in the lumen of the ER, Man(7)GlcNAc(2)-P appears in the cytosol without detectable generation of ER luminal Man(7)GlcNAc(2)-P. CONCLUSIONS AND SIGNIFICANCE: The DLO pools required for N-glycosylation and fOSGN2-P generation are functionally linked and this substantiates the hypothesis that pyrophosphatase-mediated cleavage of DLO intermediates yields recyclable dolichol-P. The kinetics of cytosolic fOSGN2-P generation from a luminally-generated DLO intermediate demonstrate the presence of a previously undetected ER-to-cytosol translocation process for either fOSGN2-P or DLO

Designing antifilarial drug trials using clinical trial simulators

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles

Etude technico-économique d'exploitations laitières en Nord Est : sonde RICA, résultats 1988

Generally, dairy farms of North-Eastern France are large farms where crops other than forage species are grown: with sometimes limited manpower, a cattle herd is raised for milk and meat production. Technical and economic results are often low when considered on a hectare basis, but they are rather favorable overall because of the farm size and the small number of workers. This global vision covers a number of situations that can be classified into three groups. The first which is the largest includes smaller, less modern farms located in the grassland areas on the North-East side. They are specialized in milk production but do produce small quantities of cattle meat. The agricultural income is average in spite of reduced operational and structure costs since the technical results are low and the number of workers high. The second group includes the larger and well-equiped farms of the Barois region with limited manpower where cereal crops represent 55% of the surface area. Intensive dairy cattle production gives good results in addition to a herd of heifers and/or bull calves for meat production. The agricultural income is higher: 151 000 F /farm - 103 600F/UTHF. The farms of the third groups are different because they are very big and have large and performing dairy cattle herds; the associated meat production is that of bull calf. The income increases with the farm size and is the highest of all groups: 267 600F/farm and 169 100F/UTHF. / Généralement, les exploitations de la sonde laitière Nord Est sont caractérisées par de grandes dimensions où les cultures non fourragères occupent parfois une place importante : elles entretiennent avec une main d'oeuvre quelquefois limitée un troupeau bovin lait auquel est souvent associée une production de viande bovine, basée sur la production de taurillons. Les résultats technico-économiques, ramenés à l'hectare, sont souvent faibles mais compensés par la dimension, ils sont par exploitation et par travailleur plutôt favorables. Cette vision globale recouvre une diversité de situations que l'on peut approcher autour de trois familles d'exploitations. La première famille, la plus nombreuse, rassemble les exploitations situées en zone herbagère du Nord-Est de plus faibles dimension (75 ha SAU), moins modernisées, plutôt spécialisées en production laitière (32 VL - 125 000 litres de lait), mais produisant aussi de la viande en petite quantité (taurillons, boeufs ou génisses). Les revenus agricoles obtenus sont modestes (95 000 F/exploitation - 57 000 F/UTH), malgré des charges opérationnelles et de structure réduites, car les résultats techniques sont faibles, et la main d'oeuvre relativement importante. La seconde famille comprend des exploitations du Barrois plus grandes (97 ha SAU) et bien équipées, à main d'oeuvre limitée, où les grandes cultures occupent plus de 55 % de la SAU. Le troupeau laitier (30 VL - 148 000 l lait) obtient de bonnes performances à partir d'une conduite intensive, et est complété par un troupeau allaitant et/ou une production de taurillons, assurant un produit viande important. Les revenus agricoles sont plus élevés : 151 000 F/exploitation - 103 600 F/UTHF. L'ensemble des exploitations de la troisième famille (où se trouve les G.A.E.C. de l'échantillon) se distingue par sa grande dimension (122 ha) et par la présence de grands troupeaux laitiers (68 VL - 337 000 litres de lait) performants et bien conduits : la production de viande associée est celle de taurillons (ou de veaux lourds). Les revenus progressent avec la dimension et sont les plus élevés de la sonde : 267 600 F/exploitation et 169 100 F/UTHF

Place de l'herbe dans les élevages bovins du Massif central nord (Auvergne et Limousin).

[Notes_IRSTEA]ann./tabl./note de synthèse 11 p.This study analyses the importance of grassland in the different types of bovine livestock farms located in Auvergne and Limousin. Breeding and fodder system define each type. The analysis is based on data from the farm network RICA 1995 (551 farms),and from the networks of bovine livestock systems followed by the Cemagref-ETCF, INRA-LEE, and Chambres d'Agriculture (135 farms). Grassland occupies 48 % of the total surface of Auvergne and 43 % of that of the Limousin: it is an important element of the landscape of these areas. The permanent grasslands hold a dominating place. These two areas obtain much grassland subsidies, which can ensure until a third of farm income. Also, precautions should be taken to avoid decreasing of grassland attraction with the next CAP reform and the CTE (Territorial Farm Contract).L'étude analyse l'importance de la surface en herbe dans les différents types d'exploitation d'élevage bovin (et aussi ovin, souvent associé aux bovins) présents en Auvergne et Limousin. Chaque type est défini par un système d'élevage et par un système fourrager, herbager ou mixte herbe et maïs fourrage plus ou moins intensif. Les données exploitées sont issues du RICA 1995, conjointement avec les données issues des réseaux d'exploitations d'élevage suivis par le Cemagref- ETCF (Elevages et Territoires), l'INRA -LEE (Laboratoire d'Economie de l'Elevage de Theix), et les Chambres d'Agriculture de l'Allier, du Cantal, de la Corrèze, de la Haute-Vienne, et du Centre d'Economie Rurale de Haute-Loire. La surface en herbe occupe 48 % de la surface totale de l'Auvergne et 43 % de celle du Limousin : c'est un élément fort du paysage de ces régions. En plus, au plan de la qualité des herbages, la prairie permanente tient une place prépondérante. L'herbe constitue la première ressource fourragère pour l'élevage bovin et ovin. Au delà des types dominants, comme les élevages bovins naisseurs producteurs de broutards herbagers extensifs_, emblématiques de ces régions, il existe d'autres types adaptés à des conditions agroclimatiques localisées, d'où une grande diversité qui se retrouve aussi dans les catégories de bovins produits souvent sous signes de qualité. Cette importance de l'élevage à l'herbe généralement peu intensif se traduit par l'obtention d'aides liées à ce mode de conduite, le supplément extensif des primes bovines et surtout la prime au maintien des systèmes d'élevage extensifs (ou prime à l'herbe) : l'Auvergne et le Limousin reçoivent près de 30 % du montant total de la prime à l'herbe. Au plan des exploitations, ces aides peuvent assurer jusqu'à un tiers du revenu, comme chez les herbagers les plus extensifs. Aussi, il faudrait veiller à ce que la réforme de la PAC en modifiant le mode de calcul du chargement administratif du Complément Extensification (qui remplace le supplément extensif), et que les CTE (Contrats Territoriaux d'Exploitation) pouvant entraîner une modification du système actuel de la prime à l'herbe, ne rendent pas moins attractive le maintien de la surface en herbe