Pathogenesis of bovine spongiform encephalopathy in sheep

The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was detected after 6 months in the tonsil and the ileal Peyer’s patches. At 9 months postinfection, PrPSc accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrPSc accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrPSc was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7–L1. At subsequent time points, PrPSc was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrPSc involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord

Uncertain groupings: probabilistic combination of grouping data

Probabilistic approaches for data integration have much potential. We view data integration as an iterative process where data understanding gradually increases as the data scientist continuously refines his view on how to deal with learned intricacies like data conflicts. This paper presents a probabilistic approach for integrating data on groupings. We focus on a bio-informatics use case concerning homology. A bio-informatician has a large number of homology data sources to choose from. To enable querying combined knowledge contained in these sources, they need to be integrated. We validate our approach by integrating three real-world biological databases on homology in three iterations

Cost-effectiveness of tailored print communication, telephone motivational interviewing, and a combination of the two: results of an economic evaluation alongside the Vitalum randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to evaluate the cost-effectiveness of tailored print communication (TPC), telephone motivational interviewing (TMI), a combination of the two, and no intervention on two outcomes in adults aged 45 to 70, half of them having hypertension: increasing the number of public health guidelines met for three behaviors (physical activity and fruit and vegetable consumption), and impact on quality adjusted life years (QALYs).</p> <p>Methods</p> <p>Participants (<it>n </it>= 1,629) from 23 Dutch general practices were randomized into one of four groups, which received 4 TPCs, 4 TMIs, 2 of each (combined), or no intervention (control), respectively. The self-reported outcomes, measured at baseline and 73 weeks follow-up (7 months after the last intervention component), were difference in total number of guidelines met at follow-up compared to baseline, and number of QALYs experienced over 73 weeks. The costs of implementing the intervention were estimated using a bottom-up approach.</p> <p>Results</p> <p>At 73 weeks follow-up participants showed increased adherence with 0.62 (TPC), 0.40 (TMI), 0.50 (combined), and 0.26 (control) guidelines compared to baseline, and experienced 1.09, 1.08, 1.08, and 1.07 QALYs, respectively. The costs for the control group were considered to be zero. TMI was more expensive (€107 per person) than both the combined intervention (€80) and TPC (€57). The control condition was most cost-effective for lower ceiling ratios, while TPC had the highest probability of being most cost-effective for higher ceiling ratios (more than €160 per additional guideline met, and €2,851 for each individual QALY).</p> <p>Conclusions</p> <p>For low society's willingness to pay, the control group was most cost-effective for the number of QALYs experienced over 73 weeks. This also applied to the increase in the number of guidelines met at lower ceiling ratios, whereas at higher ceiling ratios, TPC had a higher probability of being more cost-effective than the TMI, combined or control conditions. This also seemed to apply for QALYs experienced over 73 weeks. More research is needed on the long-term efficacy of both TPC and TMI, as well as on how to increase their cost-effectiveness.</p> <p>Trial registration</p> <p>Dutch Trial Register NTR1068</p

Sweet cherry production in South Patagonia

In South Patagonia, the total sweet cherry (Prunus avium L.) area has increased from 176 ha in 1997 to 507 ha in 2004, of which 232 ha are located in Los Antiguos (46°19¿ SL; 220 m elevation), 158 ha in the Lower Valley of Chubut River (LVCHR) (43°16¿ SL; 30 m elevation), 52 ha in Sarmiento (45°35¿ SL; 270 m elevation), 35 ha in Esquel (42°55¿ SL; 570 m elevation) and 30 ha in Comodoro Rivadavia (45°52¿ SL; 50 m elevation). The most common varieties are `Lapins¿, `Bing¿, `Newstar¿, `Sweetheart¿, `Stella¿, `Sunburst¿ and `Van¿ grafted on `Mahaleb¿, `Pontaleb¿, `SL 64¿, `Colt¿ or `Mazzard¿ rootstocks. Trees generally are drip-irrigated and planted at high densities, using training systems such as Tatura, central leader and modified vase (2700, 1100 and 1000 trees ha-1, respectively). Growers in Los Antiguos are more traditional, planting mainly as vase (400 to 1000 trees ha-1) or freestanding trees (280 trees ha-1) and irrigating by gravity (74% of the area). Only 4.4% of the area of Los Antiguos is frost protected, as growers rely strongly on the moderating effect of Lake Buenos Aires. Frost control systems are absent in Comodoro Rivadavia because the established orchards are located next to the sea, in an area with low risk of frost. The frost-protected area is 49% in Sarmiento, 35% in Esquel and 57% in LVCHR. Fruit are harvested from November (LVCHR) to the end of January (Los Antiguos and Esquel), and the harvest-only labour demand during the 2004/2005 season was 100,000 h. In that season, seven packinghouses exported 390 t (45% of the total production) to Europe. Most orchards have not yet reached their mature stage and new ones are being established. Therefore, fruit volumes will continue to increase and shortages of labour and packing facilities may become a constraint

The ambiguity of human ashes: exploring encounters with cremated remains in the Netherlands

This article explores cremation and disposal practices in the Netherlands, focusing on the attitudes and experiences of bereaved Dutch people in relation to cremated remains. In academic and professional narratives, human ashes are commonly described as “important,” as “sacred,” and as a vehicle to continue intense and physical relationships with the dead. Based on quantitative and qualitative data this article illustrates the ambiguity of such relationships. It highlights the diverse experiences, unexpected challenges, and moral obligations that can be evoked by the deceased’s ashes, where the latter are seen as embedded in material practices and entangled in social relationships

Consensus Paper: Cerebellum and Emotion

Over the past three decades, insights into the role of the cerebellum in emotional processing have substantially increased. Indeed, methodological refinements in cerebellar lesion studies and major technological advancements in the field of neuroscience are in particular responsible to an exponential growth of knowledge on the topic. It is timely to review the available data and to critically evaluate the current status of the role of the cerebellum in emotion and related domains. The main aim of this article is to present an overview of current facts and ongoing debates relating to clinical, neuroimaging, and neurophysiological findings on the role of the cerebellum in key aspects of emotion. Experts in the field of cerebellar research discuss the range of cerebellar contributions to emotion in nine topics. Topics include the role of the cerebellum in perception and recognition, forwarding and encoding of emotional information, and the experience and regulation of emotional states in relation to motor, cognitive, and social behaviors. In addition, perspectives including cerebellar involvement in emotional learning, pain, emotional aspects of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are briefly discussed. Results of this consensus paper illustrate how theory and empirical research have converged to produce a composite picture of brain topography, physiology, and function that establishes the role of the cerebellum in many aspects of emotional processing

Evaluation of a firm model in estimating aggregate supply response

The North Central Regional Research Project NC- 54, “Supply Response and Adjustments for Hog and Beef Cattle Production,” was started in 1961. The project statement lists these objectives: (1) To estimate farm resource use and supply response of hogs and beef cattle in representative farm situations. (2) To estimate total production of hogs and beef cattle and patterns of resource use for states in the North Central Region and for the nation. (3) To determine the production situations and the areas in which a specified output of hogs and beef cattle would or could be produced most efficiently under various projected levels of demand and prices and at a given level of technology representing that now known but not yet generally adopted. Linear-programming, time-series analysis, production function analysis and “outlook” research were used in the study. The linear-programming research was divided into two phases. Phase I involved (a) estimating the optimum organization and production for representative farms at various prices for hogs, cattle and feed grains and (b) aggregating these results to give estimates of regional production. The purpose of Phase II was to examine the effects of permitting acquisition and disposal of factors of production assumed fixed in the Phase I model. This was accomplished by including purchase and sale activities for fixed assets at predetermined prices. Insofar as the purchases and sales were not conducted within a framework of regional constraints and because an appropriate weighting scheme was not readily available, no aggregation of the Phase II results was made. Time-series analysis, production function analysis and “outlook” analysis were used to complement the programming analysis

Profiles of US and CT imaging features with a high probability of appendicitis

To identify and evaluate profiles of US and CT features associated with acute appendicitis. Consecutive patients presenting with acute abdominal pain at the emergency department were invited to participate in this study. All patients underwent US and CT. Imaging features known to be associated with appendicitis, and an imaging diagnosis were prospectively recorded by two independent radiologists. A final diagnosis was assigned after 6 months. Associations between appendiceal imaging features and a final diagnosis of appendicitis were evaluated with logistic regression analysis. Appendicitis was assigned to 284 of 942 evaluated patients (30%). All evaluated features were associated with appendicitis. Imaging profiles were created after multivariable logistic regression analysis. Of 147 patients with a thickened appendix, local transducer tenderness and peri-appendiceal fat infiltration on US, 139 (95%) had appendicitis. On CT, 119 patients in whom the appendix was completely visualised, thickened, with peri-appendiceal fat infiltration and appendiceal enhancement, 114 had a final diagnosis of appendicitis (96%). When at least two of these essential features were present on US or CT, sensitivity was 92% (95% CI 89-96%) and 96% (95% CI 93-98%), respectively. Most patients with appendicitis can be categorised within a few imaging profiles on US and CT. When two of the essential features are present the diagnosis of appendicitis can be made accuratel

Plasmid-mediated AmpC

_Objectives:_ The objective of this study was to determine the prevalence of pAmpC beta-lactamases in community-acquired Gram negative bacteria in the Netherlands, and to identify possible risk factors for carriage of these strains. Methods: Fecal samples were obtained from community-dwelling volunteers. Participants also returned a questionnaire for analysis of risk factors. Screening for pAmpC was performed with selective enrichment broth and a selective screening agar. Confirmation of AmpC-production was performed with two double disc combination tests: cefotaxime and ceftazidime with either boronic acid or cloxacillin as inhibitor. Multiplex PCR was used as gold standard for detection of pAmpC. 16S rRNA PCR and AFLP were performed as required, plasmids were identified by PCR-based replicon typing. Questionnaire results were analyzed with SPSS, version 20.0. Results: Fecal samples were obtained from 550 volunteers; mean age 51 years (range: 18-91), 61% were females. pAmpC was present in seven E. coli isolates (7/550, 1.3%, 0.6-2.7 95% CI): six CMY-2-like pAmpC and one DHA. ESBL-encoding genes were found in 52/550 (9.5%, 7.3-12.2 95% CI) isolates; these were predominantly blaCTX-M genes. Two isolates had both ESBL and pAmpC. Admission to a hospital in the previous year was the only risk factor we identified. Conclusions: Our data indicate that the prevalence of pAmpC in the community seems still low. However, since pAmpC-producing isolates were not identified as ESBL producers by routine algorithms, there is consistent risk that further increase of their prevalence might go undetected

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion