No alignment of cattle along geomagnetic field lines found

This paper presents a study of the body orientation of domestic cattle on free pastures in several European states, based on Google satellite photographs. In sum, 232 herds with 3412 individuals were evaluated. Two independent groups participated in our study and came to the same conclusion that, in contradiction to the recent findings of other researchers, no alignment of the animals and of their herds along geomagnetic field lines could be found. Several possible reasons for this discrepancy should be taken into account: poor quality of Google satellite photographs, difficulties in determining the body axis, selection of herds or animals within herds, lack of blinding in the evaluation, possible subconscious bias, and, most importantly, high sensitivity of the calculated main directions of the Rayleigh vectors to some kind of bias or to some overlooked or ignored confounder. This factor could easily have led to an unsubstantiated positive conclusion about the existence of magnetoreception.Comment: Added electronic supplement with source dat

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1

Increased expression of BAFF (B cell-activating factor belonging to the TNF family) and its receptors has been identified in numerous B-cell malignancies. A soluble human BAFF mutant (mBAFF), binding to BAFF receptors but failing to activate B-lymphocyte proliferation, may function as a competitive inhibitor of BAFF and may serve as a novel ligand for targeted therapy of BAFF receptor-positive malignancies. Pin2/TRF1-interacting protein X1 (PinX1), a nucleolar protein, potently inhibits telomerase activity and affects tumorigenicity. In this study, we generated novel recombinant proteins containing mBAFF, a polyarginine tract 9R and PinX1 (or its C/N terminal), to target lymphoma cells. The fusion proteins PinX1/C–G4S–9R–G4S–mBAFF and PinX1/C–9R–mBAFF specifically bind and internalize into BAFF receptor-positive cells, and subsequently induce growth inhibition and apoptosis. The selective cytotoxicity of the fusion proteins is a BAFF receptor-mediated process and depends on mBAFF, PinX1/C and 9R. Moreover, the fusion proteins specifically kill BAFF receptor-expressing Burkitt's lymphoma (BL) cells by inhibiting telomerase activity and the consequent shortening of telomeres. Therapeutic experiments using PinX1C–G4S–9R–G4S–mBAFF in severe combined immunodeficient (SCID) mice implanted with Raji cells showed significantly prolonged survival times, indicating the in vivo antitumor activity of the fusion protein. These results suggest the potential of PinX1/C–G4S–9R–G4S–mBAFF in targeted therapy of BL

Stochastic Modelling: From Pattern Classification to Speech Recognition and Language Translation

This paper gives an overview of the stochastic modelling approach to machine translation. Starting with the Bayes decision rule as in pattern classification and speech recognition, we show how the resulting system architecture can be structured into three parts: the language model probability, the string translation model probability and the search procedure that gener-ates the word sequence in the target language. We discuss the properties of the system components and report results on the translation of spoken dialogues in the VERBMOBIL project. The experience obtained in the VERB-MOBIL project, in particular a large-scale end-to-end evaluation, showed that the stochastic modelling approach resulted in significantly lower error rates than three competing translation approaches: the sentence error rate was 29 % in comparison with 52 % to 62% for the other translation approaches.

Reliability of Rapid Diagnostic Tests in Diagnosing Pregnancy-Associated Malaria in North-Eastern Tanzania.

Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen™) or HRP-2 only (Paracheck Pf® and ParaHIT®f), microscopy and nested Plasmodium species diagnostic PCR. From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 -1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in Tsetse in Serengeti, Tanzania

Background: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. Methodology/Principal Findings: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0–0.085) for G. swynnertoni and 0% (0–0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0–0.054) and 0.0089% (0–0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. Conclusions/Significance: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data

Dietary responses to a multiple sclerosis diagnosis: a qualitative study

Background/objectives: Multiple sclerosis (MS) is an immune-mediated disease with no known cure and insufficient evidence to support a special therapeutic diet to alter symptom management or disease progression. Several studies have reported dietary changes made by people with MS, but there has been limited investigation into experiences surrounding diet in those recently diagnosed. This study explored responses to diet after a recent diagnosis of MS in people living in Western Australia. Subjects/methods: Eleven adults with MS (mean time since diagnosis 8 months) participated in semi-structured interviews focusing on responses to diet since MS diagnosis. Interviews were transcribed, coded and analysed using grounded theory principles. Results: Three theme responses emerged; (1) the perceived incompatibility of lack of/or generalised dietary advice with disease seriousness at the time of diagnosis; (2) extensive personal research and information seeking with difficulty judging credibility, and (3) self-experimentation with diet to either control MS symptoms or to cure MS. Conclusions: Given the seriousness of the disease, there is a perceived gap in dietary information provided at the time of diagnosis. Healthcare professionals should address concerns with alternative therapeutic diets advertised to treat or cure MS, and clearly convey the reasoning for the general healthy dietary recommendations. This would better align advice with the perceptions about the role of diet in MS, assist people with MS in need of information and minimise dietary self-experimentation. Future research should explore the importance of diet for those who have had MS for a longer period of time

Toward a Surrogate Marker of Malaria Exposure: Modeling Longitudinal Antibody Measurements under Outbreak Conditions

Background: Biomarkers of exposure to Plasmodium falciparum would be a useful tool for the assessment of malaria burden and analysis of intervention and epidemiological studies. Antibodies to pre-erythrocytic antigens represent potential surrogates of exposure. Methods and Findings: In an outbreak cohort of U.S. Marines deployed to Liberia, we modeled pre- and post-deployment IgG against P. falciparum sporozoites by immunofluorescence antibody test, and both IgG and IgM against the P. falciparum circumsporozoite protein by enzyme-linked immunosorbant assay. Modeling seroconversion thresholds by a fixed ratio, linear regression or nonlinear regression produced sensitivity for identification of exposed U.S. Marines between 58-70% and specificities between 87-97%, compared with malaria-naïve U.S. volunteers. Exposure was predicted in 30-45% of the cohort. Conclusion: Each of the three models tested has merits in different studies, but further development and validation in endemic populations is required. Overall, these models provide support for an antibody-based surrogate marker of exposure to malaria

Examining appropriate diagnosis and treatment of malaria: availability and use of rapid diagnostic tests and artemisinin-based combination therapy in public and private health facilities in south east Nigeria

<p>Abstract</p> <p>Background</p> <p>Rapid diagnostic tests (RDTs) and Artemisinin-based combination therapy (ACT) have been widely advocated by government and the international community as cost-effective tools for diagnosis and treatment of malaria. ACTs are now the first line treatment drug for malaria in Nigeria and RDTs have been introduced by the government to bridge the existing gaps in proper diagnosis. However, it is not known how readily available these RDTs and ACTs are in public and private health facilities and whether health workers are actually using them. Hence, this study investigated the levels of availability and use of RDTs and ACTs in these facilities.</p> <p>Methods</p> <p>The study was undertaken in Enugu state, southeast Nigeria in March 2009. Data was collected from heads of 74 public and private health facilities on the availability and use of RDTs and ACTs. Also, the availability of RDTs and the types of ACTs that were available in the facilities were documented.</p> <p>Results</p> <p>Only 31.1% of the health facilities used RDTs to diagnose malaria. The majority used the syndromic approach. However, 61.1% of healthcare providers were aware of RDTs. RDTs were available in 53.3% of the facilities. Public health facilities and health facilities in the urban areas were using RDTs more and these were mainly bought from pharmacy shops and supplied by NGOs. The main reasons given for non use are unreliability of RDTs, supply issues, costs, preference for other methods of diagnosis and providers' ignorance. ACTs were the drug of choice for most public health facilities and the drugs were readily available in these facilities.</p> <p>Conclusion</p> <p>Although many providers were knowledgeable about RDTs, not many facilities used it. ACTS were readily available and used in public but not private health facilities. However, the reported use of ACTs with limited proper diagnosis implies that there could be high incidence of inappropriate case management of malaria which can also increase the economic burden of illnesses. Government and donors should ensure constant availability of RDTs in both public and private facilities, so that every treatment with ACTs is accompanied with proper diagnosis.</p