Rickettsia typhi IN RODENTS AND R. felis IN FLEAS IN YUCATÁN AS A POSSIBLE CAUSAL AGENT OF UNDEFINED FEBRILE CASES

Rickettsia typhi is the causal agent of murine typhus; a worldwide zoonotic and vector-borne infectious disease, commonly associated with the presence of domestic and wild rodents. Human cases of murine typhus in the state of Yucatán are frequent. However, there is no evidence of the presence of Rickettsia typhi in mammals or vectors in Yucatán. The presence of Rickettsia in rodents and their ectoparasites was evaluated in a small municipality of Yucatán using the conventional polymerase chain reaction technique and sequencing. The study only identified the presence of Rickettsia typhi in blood samples obtained from Rattus rattus and it reported, for the first time, the presence of R. felis in the flea Polygenis odiosus collected from Ototylomys phyllotis rodent. Additionally, Rickettsia felis was detected in the ectoparasite Ctenocephalides felis fleas parasitizing the wild rodent Peromyscus yucatanicus. This study’s results contributed to a better knowledge of Rickettsia epidemiology in Yucatán.

The presence of Lutzomyia longipalpis in a focus of American visceral leishmaniasis where the only proven vector is Lutzomyia cruzi. Corumbá, Mato Grosso do Sul State

The present communication reports the presence of Lutzomyia longipalpis in Corumbá, Mato Grosso do Sul, where the principal vector is Lutzomyia cruzi.

Towards an algorithmic skeleton framework for programming the Intel R Xeon PhiTM processor

The Intel R Xeon PhiTM is the first processor based on Intel’s MIC (Many Integrated Cores) architecture. It is a co-processor specially tailored for data-parallel computations, whose basic architectural design is similar to the ones of GPUs (Graphics Processing Units), leveraging the use of many integrated low computational cores to perform parallel computations. The main novelty of the MIC architecture, relatively to GPUs, is its compatibility with the Intel x86 architecture. This enables the use of many of the tools commonly available for the parallel programming of x86-based architectures, which may lead to a smaller learning curve. However, programming the Xeon Phi still entails aspects intrinsic to accelerator-based computing, in general, and to the MIC architecture, in particular. In this thesis we advocate the use of algorithmic skeletons for programming the Xeon Phi. Algorithmic skeletons abstract the complexity inherent to parallel programming, hiding details such as resource management, parallel decomposition, inter-execution flow communication, thus removing these concerns from the programmer’s mind. In this context, the goal of the thesis is to lay the foundations for the development of a simple but powerful and efficient skeleton framework for the programming of the Xeon Phi processor. For this purpose we build upon Marrow, an existing framework for the orchestration of OpenCLTM computations in multi-GPU and CPU environments. We extend Marrow to execute both OpenCL and C++ parallel computations on the Xeon Phi. We evaluate the newly developed framework, several well-known benchmarks, like Saxpy and N-Body, will be used to compare, not only its performance to the existing framework when executing on the co-processor, but also to assess the performance on the Xeon Phi versus a multi-GPU environment.

The existence of only one haplotype of Leishmania major in the main and potential reservoir hosts of zoonotic cutaneous leishmaniasis using different molecular markers in a focal area in Iran

IntroductionLeishmania major is the causative agent of zoonotic cutaneous leishmaniasis (ZCL), and great gerbils are the main reservoir hosts in Iran. Abarkouh in central Iran is an emerging focal point for which the reservoir hosts of ZCL are unclear. This research project was designed to detect any Leishmania parasites in different wild rodent species.MethodsAll rodents captured in 2011 and 2012 from Abarkouh district were identified based on morphological characteristics and by amplification of the rodent cytochrome b (Cyt b) gene. To detect Leishmania infection in rodents, deoxyribonucleic acid (DNA) of each ear was extracted. Internal transcribed spacer-ribosomal deoxyribonucleic acid (ITS-rDNA), microsatellites, kinetoplast deoxyribonucleic acid (kDNA) and cytochrome b genes of Leishmania parasites were amplified by polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) and sequencing were employed to confirm the Leishmania identification.ResultsOf 68 captured rodents in the region, 55 Rhombomys opimus were identified and nine Leishmaniainfections (9/55) were found. In addition, eight Meriones libycus and two Tatera indicawere sampled, and one of each was confirmed to be infected. Two Meriones persicus and one Mus musculuswere sampled with no infection.ConclusionsThe results showed that all 11 unambiguously positive Leishmania infections were Leishmania major. Only one haplotype of L. major(GenBank access No. EF413075) was found and at least three rodents R. opimus, M. libycus and T. indica—appear to be the main and potential reservoir hosts in this ZCL focus. The reservoir hosts are variable and versatile in small ZCL focal locations.

Endogeneizing know-how flows through the nature of R&D investments

In this paper we carefully link knowledge flows to and from a firms innovation process with this firms investment decisions. Three types of investments are considered: investments in applied research, investments in basic research, and investments in intellectual property protection. Only when basic research is performed, can the firm effectively access incoming knowledge flows and these incoming spillovers serve to increase the efficiency of own applied research.. The firm can at the same time influence outgoing knowledge flows, improving appropriability of its innovations, by investing in protection. Our results indicate that firms with small budgets for innovation will not invest in basic research. This occurs in the short run, when the budget for know-how creation is restricted, or in the long-run, when market opportunities are low, when legal protection is not very important, or, when the pool of accessible and relevant external know-how is limited. The ratio! of basic to applied research is non-decreasing in the size of the pool of accessible external know-how, the size and opportunity of the market, and, the effectiveness of intellectual property rights protection. This indicates the existence of economies of scale in basic research due to external market related factors. Empirical evidence from a sample of innovative manufacturing firms in Belgium confirms the economies of scale in basic research as a consequence of the firms capacity to access external knowledge flows and to protect intellectual property, as well as the complementarity between legal and strategic investments.

Y-90-Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

The link between public support and private R&D effort: What is the optimal subsidy?

The effectiveness of R&D subsidies can vary substantially depending on their characteristics. Specifically, the amount and intensity of such subsidies are crucial issues in the design of public schemes supporting private R&D. Public agencies determine the intensities of R&D subsidies for firms in line with their eligibility criteria, although assessing the effects of R&D projects accurately is far from straightforward. The main aim of this paper is to examine whether there is an optimal intensity for R&D subsidies through an analysis of their impact on private R&D effort. We examine the decisions of a public agency to grant subsidies taking into account not only the characteristics of the firms but also, as few previous studies have done to date, those of the R&D projects. In determining the optimal subsidy we use both parametric and nonparametric techniques. The results show a non-linear relationship between the percentage of subsidy received and the firms’ R&D effort. These results have implications for technology policy, particularly for the design of R&D subsidies that ensure enhanced effectiveness.

The determinants of YIc's R&D activity

This paper examines the determinants of young innovative companies’ (YICs) R&D activities taking into account the autoregressive nature of innovation. Using a large longitudinal dataset comprising Spanish manufacturing firms over the period 1990-2008, we find that previous R&D experience is a fundamental determinant for mature and young firms, albeit to a smaller extent in the case of the YICs, suggesting that their innovation behaviour is less persistent and more erratic. Moreover, our results suggest that firm and market characteristics play a distinct role in boosting the innovation activity of firms of different age. In particular, while market concentration and the degree of product diversification are found to be important in boosting R&D activities in the sub-sample of mature firms only, YICs’ spending on R&D appears to be more sensitive to demand-pull variables, suggesting the presence of credit constraints. These results have been obtained using a recently proposed dynamic type-2 tobit estimator, which accounts for individual effects and efficiently handles the initial conditions problem.

Rhodnius amazonicus Almeida, Santos & Sposina, 1973, Bona Species, Close to R. pictipes Stål, 1872 (Heteroptera, Reduviidae, Triatominae)

The discovery of two atypical specimens of Rhodnius pictipes Stål, 1872 in French Guiana and the examination of the female holotype of R. amazonicus Almeida, Santos & Sposina, 1973, the only specimen of this species so far known, lead us to propose the rehabilitation of R. amazonicus synonymized with R. pictipes. The male is described for the first time and the female redescribed. Both external characters and genitalia distinguish R. amazonicus from R. pictipes. R. amazonicus shows affinities not only with pictipes but also with R. stali Lent, Jurberg & Galvão, 1993 and R. paraensis Sherlock, Guitton & Miles, 1977. A key is provided for these four species forming, in all likelihood, a natural group, i.e. the "pictipes group".

Local Distance-Based Generalized Linear Models using the dbstats package for R

This paper introduces local distance-based generalized linear models. These models extend (weighted) distance-based linear models firstly with the generalized linear model concept, then by localizing. Distances between individuals are the only predictor information needed to fit these models. Therefore they are applicable to mixed (qualitative and quantitative) explanatory variables or when the regressor is of functional type. Models can be fitted and analysed with the R package dbstats, which implements several distancebased prediction methods.

Modular analysis of gene expression data with R.

SUMMARY: Large sets of data, such as expression profiles from many samples, require analytic tools to reduce their complexity. The Iterative Signature Algorithm (ISA) is a biclustering algorithm. It was designed to decompose a large set of data into so-called 'modules'. In the context of gene expression data, these modules consist of subsets of genes that exhibit a coherent expression profile only over a subset of microarray experiments. Genes and arrays may be attributed to multiple modules and the level of required coherence can be varied resulting in different 'resolutions' of the modular mapping. In this short note, we introduce two BioConductor software packages written in GNU R: The isa2 package includes an optimized implementation of the ISA and the eisa package provides a convenient interface to run the ISA, visualize its output and put the biclusters into biological context. Potential users of these packages are all R and BioConductor users dealing with tabular (e.g. gene expression) data. AVAILABILITY: http://www.unil.ch/cbg/ISA CONTACT: sven.bergmann@unil.ch

Mixed-function oxidases and esterases associated with cross-r esistance between DDT and lambda-cyhalothrin in Anopheles darlingi Root 1926 populations from Colombia

In order to establish the insecticide susceptibility status for Anopheles darlingi in Colombia, and as part of the National Network on Insecticide Resistance Surveillance, five populations of insects from three Colombian states were evaluated. Standardised WHO and CDC bottle bioassays, in addition to microplate biochemical assays, were conducted. Populations with mortality rates below 80% in the bioassays were considered resistant. All field populations were susceptible to deltamethrin, permethrin, malathion and fenitrothion. Resistance to lambda-cyhalothrin and DDT was detected in the Amé-Beté population using both bioassay methods with mortality rates of 65-75%. Enzyme levels related to insecticide resistance, including mixed function oxidases (MFO), non-specific esterases (NSE), glutathione S-transferases and modified acetylcholinesterase were evaluated in all populations and compared with a susceptible natural strain. Only mosquitoes from Amé-Beté presented significantly increased levels of both MFO and NSE, consistent with the low mortalities found in this population. The continued use of lambda-cyhalothrin for An. darlingi control in this locality has resulted in a natural resistance to this insecticide. In addition, DDT resistance is still present in this population, although this insecticide has not been used in Colombia since 1992. Increased metabolism through MFO and NSE may be involved in cross-resistance between lambda-cyhalothrin and DDT, although kdr-type nerve insensitivity cannot be discarded as a possible hypothesis. Additional research, including development of a kdr specific assay for An. darlingi should be conducted in future studies. Our data demonstrates the urgent need to develop local insecticide resistance management and surveillance programs throughout Colombia.

Y-90 Ibritumomab Tiuxetan (Zevalin (R)) Consolidation of First Remission In Advanced Stage Follicular Non Hodgkin's Lymphoma Updated Results After a Median Follow up of 662 Months From the International, Randomized, Phase III First Line Indolent Trial (FIT) In 414 Patients

The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39-0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42-0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27-0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30-1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were - for the greater part - rituximab-naïve.

News from compositions, the R package

The R-package “compositions”is a tool for advanced compositional analysis. Its basicfunctionality has seen some conceptual improvement, containing now some facilitiesto work with and represent ilr bases built from balances, and an elaborated subsys-tem for dealing with several kinds of irregular data: (rounded or structural) zeroes,incomplete observations and outliers. The general approach to these irregularities isbased on subcompositions: for an irregular datum, one can distinguish a “regular” sub-composition (where all parts are actually observed and the datum behaves typically)and a “problematic” subcomposition (with those unobserved, zero or rounded parts, orelse where the datum shows an erratic or atypical behaviour). Systematic classificationschemes are proposed for both outliers and missing values (including zeros) focusing onthe nature of irregularities in the datum subcomposition(s).To compute statistics with values missing at random and structural zeros, a projectionapproach is implemented: a given datum contributes to the estimation of the desiredparameters only on the subcompositon where it was observed. For data sets withvalues below the detection limit, two different approaches are provided: the well-knownimputation technique, and also the projection approach.To compute statistics in the presence of outliers, robust statistics are adapted to thecharacteristics of compositional data, based on the minimum covariance determinantapproach. The outlier classification is based on four different models of outlier occur-rence and Monte-Carlo-based tests for their characterization. Furthermore the packageprovides special plots helping to understand the nature of outliers in the dataset.Keywords: coda-dendrogram, lost values, MAR, missing data, MCD estimator,robustness, rounded zeros

Comparison of the NEO-FFI, the NEO-FFI-R and an alternative short version of the NEO-PI-R (NEO-60) in Swiss and Spanish samples

Three different short versions of the NEO-PI-R were compared: The NEO-FFI, the NEO-FFI-R, and a new short version developed in the current study (NEO-60). This new version is intended to improve the psychometric characteristics of the original NEO-FFI, specially in regard to the factor structure at the item-level. A French version of the NEO-PI-R was given to 1090 Swiss subjects, whereas the Spanish (Castilian) version of the NEO-PI-R was administered to 1006 Spanish subjects. Results replicate the limitations of the NEO-FFI already found in other countries. Compared to the NEO-FFI, reliability coefficients and factor structure was enhanced by the NEO-FFI-R and the NEO-60 in both samples, although substantial differences were not found. The factor structure of the NEO-60 shows the best fit since only three items do not load mainly on their own factor in both samples. Besides, correlations between items and NEO-PI-R domain scores are also higher for the items included in the NEO-60 version. On the other hand, convergent correlations with the NEO-PI-R dimensions were satisfactory irrespective of the version, and confirmatory factor analyses show slight differences among the different models generated after the three short versions.