Does Quality Influence the Required Capacity of Business Information Management? The Case of Agriculture

In order to be able to optimise the usage of IS/IT services within an organization, the Business Information Management (BIM) role is pivotal. Many organizations struggle to determine what the required number of staff for the BIM department should be. In earlier research a preliminary model to determine the required capacity of BIM was designed. In this paper the model is validated within a specific industry: the agricultural sector. From a sense that quality of IS/IT services might influence the relationship between the determining factors in the model and the required capacity for BIM, also research is conducted to analyse if quality of IS/IT service interferes with determining the required BIM capacity. As part of a literature study seven aspects of quality were found which provide a good overview of the quality of the IS/IT service within an organization. These seven aspects were included in a survey which had 37 respondents from organizations within the agricultural sector. Data was collected about a set of eight determining factors that were taken from prior research and about quality of IS/IT. Based upon these data correlations were tested. The first connections were tested by using Pearson’s product-moment correlation coefficient which showed a significant correlation between several factors and the number of FTEs. After which a multiple regression-analysis was done to check if the number of FTEs for the executive processes would increase or decrease when the number of business processes increases or decreases. The quality of the IS/IT service doesn’t seem to influence the relationship between the several factors and the number of FTEs investigated in this research. This research shows that the quality of IS/IT service has no influence on determining the required capacity of a BIM department

Viral Hepatitis C Therapy: Pharmacokinetic and Pharmacodynamic Considerations: A 2019 Update

Contains fulltext : 208854.pdf (publisher's version ) (Open Access)It has been estimated by the World Health Organization (WHO) that over 71 million people were infected with the hepatitis C virus (HCV) in 2015. Since then, a number of highly effective direct-acting antiviral (DAA) regimens have been licensed for the treatment of chronic HCV infection: sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir. With these treatment regimens, almost all chronic HCV-infected patients, even including prior DAA failures, can be treated effectively and safely. It is therefore likely that further development of DAAs will be limited. In this descriptive review we provide an overview of the clinical pharmacokinetic characteristics of currently available DAAs by describing their absorption, distribution, metabolism, and excretion. Potential drug-drug interactions with the DAAs are briefly discussed. Furthermore, we summarize what is known about the pharmacodynamics of the DAAs in terms of efficacy and safety. We briefly discuss the relationship between the pharmacokinetics of the DAAs and efficacy or toxicity in special populations, such as hard to cure patients and patients with liver cirrhosis, liver transplantation, renal impairment, hepatitis B virus or HIV co-infection, bleeding disorders, and children. The aim of this overview is to educate/update prescribers and pharmacists so that they are able to safely and effectively treat HCV-infected patients even in the presence of underlying co-infections or co-morbidities

A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

Background:Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets(ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of theircombined use.Methods:1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC)visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess thesafety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.Findings:Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence atdelivery (RR, 0.92 [95% CI, 0.79-1.08]), low birth weight (RR, 0.99 [95% CI, 0.70-1.39]), or overall placental infection(p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020) in the incidence of clinicalmalaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p,0.001), and ofactively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderlinestatistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN's use was morethan 90% in both groups.Conclusions:Two-dose SP was associated with a reduction in some indicators, but these were not translated to significantimprovement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administerIPTp. ITNs should be part of the ANC package in sub-Saharan Afric

Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio

R-spondin-3 is an oncogenic driver of poorly differentiated invasive breast cancer

R-spondins (RSPOs) are influential signaling molecules that promote the Wnt/β-catenin pathway and self-renewal of stem cells. Currently, RSPOs are emerging as clinically relevant oncogenes, being linked to cancer development in multiple organs. Although this has instigated the rapid development and testing of therapeutic antibodies targeting RSPOs, functional evidence that RSPO causally drives cancer has focused primarily on the intestinal tract. Here, we assess the oncogenic capacity of RSPO in breast cancer in a direct fashion by generating and characterizing a novel mouse model with conditional Rspo3 expression in the mammary gland. We also address the prevalence of RSPO gene alterations in breast cancer patients. We found that a quarter of breast cancer patients harbor RSPO2/RSPO3 copy number amplifications, which are associated with lack of steroid hormone receptor expression and reduced patient survival. Foremost, we demonstrate the causal oncogenic capacity of RSPO3 in the breast, as conditional Rspo3 overexpression consistently drives the development of mammary adenocarcinomas in our novel Rspo3 breast cancer model. RSPO3-driven mammary tumors typically show poor differentiation, areas of epithelial-to-mesenchymal transition, and metastatic potential. Given the reported interplay in the Wnt/β-catenin pathway, we comparatively analyzed RSPO3-driven mouse mammary tumors versus classical WNT1-driven analogues. This revealed that RSPO3-driven tumors are distinct, as the poorly differentiated tumor morphology and metastatic potential were observed in RSPO3-driven tumorigenesis exclusively, further substantiated by differentiating gene expression profiles. Co-expression of Rspo3 and Wnt1 transduced mammary tumors with a mixed phenotype harboring morphological features characteristic of both transgenes. In summary, we report that a quarter of breast cancer patients harbor RSPO2/RSPO3 copy number gains, and these patients have a worse prognosis, whilst providing in vivo evidence that RSPO3 drives poorly differentiated invasive breast cancer in mice. Herewith, we establish RSPO3 as a driver of breast cancer with clinical relevance, proposing RSPO3 as a novel candidate target for therapy in breast cancer

The effect of monthly sulfadoxine-pyrimethamine, alone or with azithromycin, on pcr-diagnosed malaria at delivery: A randomized controlled trial

10.1371/journal.pone.0041123PLoS ONE77

An analysis of the temperature dependence of force, during steady shortening at different velocities, in (mammalian) fast muscle fibres

We examined, over a wide range of temperatures (10–35°C), the isometric tension and tension during ramp shortening at different velocities (0.2–4 L0/s) in tetanized intact fibre bundles from a rat fast (flexor hallucis brevis) muscle; fibre length (L0) was 2.2 mm and sarcomere length ~2.5 μm. During a ramp shortening, the tension change showed an initial inflection of small amplitude (P1), followed by a larger exponential decline towards an approximate steady level; the tension continued to decline slowly afterwards and the approximate steady tension at a given velocity was estimated as the tension (P2) at the point of intersection between two linear slopes, as previously described (Roots et al. 2007). At a given temperature, the tension P2 declined to a lower level and at a faster rate (from an exponential curve fit) as the shortening velocity was increased; the temperature sensitivity of the rate of tension decline during ramp shortening at different velocities was low (Q10 0.9–1.5). The isometric tension and the P2 tension at a given shortening velocity increased with warming so that the relation between tension and (reciprocal) temperature was sigmoidal in both. In isometric muscle, the temperature T0.5 for half-maximal tension was ~10°C, activation enthalpy change (∆H) was ~100 kJ mol−1 and entropy change (∆S) ~350 J mol−1 K−1. In shortening, these were increased with increase of velocity so that at a shortening velocity (~4 L0/s) producing maximal power at 35°C, T0.5 was ~28°C, ∆H was ~200 kJ mol−1 and ∆S ~ 700 J mol−1 K−1; the same trends were seen in the tension data from isotonic release experiments on intact muscle and in ramp shortening experiments on maximally Ca-activated skinned fibres. In general, our findings show that the sigmoidal relation between force and temperature can be extended from isometric to shortening muscle; the implications of the findings are discussed in relation to the crossbridge cycle. The data indicate that the endothermic, entropy driven process that underlies crossbridge force generation in isometric muscle (Zhao and Kawai 1994; Davis, 1998) is even more pronounced in shortening muscle, i.e. when doing external work

Inter-Allelic Prion Propagation Reveals Conformational Relationships among a Multitude of [PSI] Strains

Immense diversity of prion strains is observed, but its underlying mechanism is less clear. Three [PSI] prion strains—named VH, VK, and VL—were previously isolated in the wild-type yeast genetic background. Here we report the generation and characterization of eight new [PSI] isolates, obtained by propagating the wild-type strains with Sup35 proteins containing single amino-acid alterations. The VH strain splits into two distinct strains when propagated in each of the three genetic backgrounds, harboring respectively single mutations of N21L, R28P, and Gi47 (i.e. insertion of a glycine residue at position 47) on the Sup35 N-terminal prion-forming segment. The six new strains exhibit complex inter-conversion patterns, and one of them continuously mutates into another. However, when they are introduced back into the wild-type background, all 6 strains revert to the VH strain. We obtain two more [PSI] isolates by propagating VK and VL with the Gi47 and N21L backgrounds, respectively. The two isolates do not transmit to other mutant backgrounds but revert to their parental strains in the wild-type background. Our data indicate that a large number of [PSI] strains can be built on three basic Sup35 amyloid structures. It is proposed that the three basic structures differ by chain folding topologies, and sub-strains with the same topology differ in distinct ways by local structural adjustments. This “large number of variations on a small number of basic themes” may also be operative in generating strain diversities in other prion elements. It thus suggests a possible general scheme to classify a multitude of prion strains

In silico modeling indicates the development of HIV-1 resistance to multiple shRNA gene therapy differs to standard antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Gene therapy has the potential to counter problems that still hamper standard HIV antiretroviral therapy, such as toxicity, patient adherence and the development of resistance. RNA interference can suppress HIV replication as a gene therapeutic via expressed short hairpin RNAs (shRNAs). It is now clear that multiple shRNAs will likely be required to suppress infection and prevent the emergence of resistant virus.</p> <p>Results</p> <p>We have developed the first biologically relevant stochastic model in which multiple shRNAs are introduced into CD34+ hematopoietic stem cells. This model has been used to track the production of gene-containing CD4+ T cells, the degree of HIV infection, and the development of HIV resistance in lymphoid tissue for 13 years. In this model, we found that at least four active shRNAs were required to suppress HIV infection/replication effectively and prevent the development of resistance. The inhibition of incoming virus was shown to be critical for effective treatment. The low potential for resistance development that we found is largely due to a pool of replicating wild-type HIV that is maintained in non-gene containing CD4+ T cells. This wild-type HIV effectively out-competes emerging viral strains, maintaining the viral <it>status quo</it>.</p> <p>Conclusions</p> <p>The presence of a group of cells that lack the gene therapeutic and is available for infection by wild-type virus appears to mitigate the development of resistance observed with systemic antiretroviral therapy.</p