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PURPOSE In the Brazilian public healthcare system, natalizumab is recommended as fourth-line treatment for relapsing-remitting multiple sclerosis (RRMS). Although natalizumab has already demonstrated higher effectiveness compared with fingolimod in some studies, this real-world study was conducted to evaluate annualized hospitalization rates (AHR) in Brazil for both treatments when switching from platform therapies. As secondary goals, we analyzed RRMS treatment patterns and hospitalization profiles. MATERIAL AND METHODS We extracted data from the DATASUS database of patients with MS (ICD-10 G35) who initiated treatment from January 2012 to December 2017. Two cohorts were screened for different purposes. Cohort 1 was used to analyze treatment patterns and hospitalization profiles and was defined as individuals who had at least one claim related to MS therapies and had received at least two lines of treatment. The second cohort, which was a subset of the first, was used to compare natalizumab's and fingolimod'is study also provide information to support disease management and healthcare planning in the Brazilian public healthcare system.Geography, including climatic factors, have long been considered potentially important elements in shaping socio-economic activities, alongside other determinants, such as institutions. Here we demonstrate that geography and climate variables satisfactorily explain the worldwide economic activity as measured by the per capita Gross Cell Product (GCP-PC) at a fine geographical resolution, typically much higher than country average. A 1° by 1° GCP-PC dataset has been key for establishing and testing a direct relationship between 'local' geography/climate and GCP-PC. Not only have we tested the geography and climate hypothesis using many possible explanatory variables, importantly we have also predicted and reconstructed GCP-PC worldwide by retaining the most significant predictors. this website While this study confirms that latitude is the most important predictor for GCP-PC when taken in isolation, the accuracy of the GCP-PC prediction is greatly improved when other factors mainly related to variations in climatic variables, rather than average climatic conditions as typically used, are considered. However, latitude diminishes in importance when only the wealthier parts of the globe are considered. This work points to specific features of the climate system which explain economic activity, such as the variability in air pressure. Implications of these findings range from an improved understanding of why socio-economically better-off societies are geographically placed where they are in the present, past and future to informing where new economic activities could be established in order to yield favourable economic outcomes based on geography and climate conditions.BACKGROUND Aortic stenosis (AS) may lead to diastolic dysfunction and later on heart failure (HF) with preserved left ventricular ejection fraction (HFpEF) via increased afterload and left-ventricular (LV) hypertrophy. Since epicardial adipose tissue (EAT) is a metabolically active fat depot that is adjacent to the myocardium and can influence cardiomyocytes and LV function via secretion of proinflammatory cytokines, we hypothesized that high amounts of EAT, as assessed by computed tomography (CT), may aggravate the development and severity of LV hypertrophy and diastolic dysfunction in the context of AS. METHODS We studied 50 patients (mean age 71 ± 9 years; 9 women) in this preliminary study with mild or moderate AS and mild to severe LV diastolic dysfunction (LVDD), diagnosed by echocardiography, who underwent non-contrast cardiac CT and echocardiography. EAT parameters were measured on 2nd generation dual source CT. Conventional two-dimensional echocardiography and Tissue Doppler Imaging (TDI) was performed to assess LV function and to derive myocardial straining parameter. All patients had a preserved LV ejection fraction > 50%. Data was analysed using Pearson's correlation. RESULTS Only weak correlation was found between EAT volume or density and E/é ratio as LVDD marker (r = -.113 p = .433 and r = .260, p = .068 respectively). Also, EAT volume or density were independent from Global Strain Parameters (r = 0.058 p = .688 and r = -0.207 p = .239). E/é ratio was strongly associated with LVDD (r = .761 p≤0.0001) and Strain Parameters were moderately associated with LV Ejection Fraction (r = -.669 p≤0.001 and r = -.454 P≤0.005). CONCLUSIONS In this preliminary study in patients with AS, the EAT volume and density as assessed by CT correlated only weakly with LVDD, as expressed by the commonly used E/é ratio, and with LV strain function. Hence, measuring EAT volume and density may neither contribute to the prediction nor upon the severity of LVDD, respectively.In conservation agriculture systems, farmers gain many advantages from retaining crop residue on the soil surface, but crop residue retention in these systems may intervene with the activity of pre-emergence herbicides. A pot study was conducted to evaluate the effect of different rates of pre-emergence herbicides [imazethapyr (100 and 150 g a. link2 i. ha-1), isoxaflutole (100 and 200 g a. i. ha-1), metolachlor (1.5 and 2.25 kg a. i. ha-1), pendimethalin (2.25 and 3.38 kg a. i. ha-1) and prosulfocarb + metolachlor (2.5 and 3.75 kg a. i. ha-1)] on seedling emergence and biomass of Echinochloa colona and Chloris virgata when applied in the presence of sorghum residue at rates equivalent to (0, 3 and 6 t ha-1). When seeds of E. colona and C. virgata were not covered with sorghum residue, the seedling emergence and biomass of both weeds was inhibited by 93-100% and 56-100%, respectively, with the application (both rates) of isoxaflutole, metolachlor, pendimethalin and prosulfocarb + metolachlor. Using sorghum residue resulted in lower herbicide efficacy on both weeds. At 3 t ha-1 sorghum residue, E. link3 colona emergence and biomass reduced by 38-100% and 30-100%, respectively, with application of isoxaflutole, metolachlor and pendimethalin (both rates) in comparison with the no-herbicide treatment. Similarly, the emergence and biomass of C. virgata was also reduced by 92-100% and 25-100%, respectively. The results of this study suggest that crop residue may influence efficacy of commonly used pre-emergence herbicides and that the amount of crop residue on the soil surface should be adjusted according to the nature of the pre-emergence herbicides to achieve adequate weed control.Language is critical to coordination in groups. Though, how language affects coordination in groups is not well understood. We prime distributive and integrative language in a bargaining experiment to better understand the links between group outcomes and communication. We accomplish this by priming interests or positions language in randomized groups. We find that priming positions as opposed to interests language leads to agreements where controllers, subjects with unilateral authority over the group outcome, receive a larger share of the benefits but where the total benefits to the group are unaffected. In contrast to common justifications for the use of integrative language in bargaining, our experimental approach revealed no significant differences between priming interests and positions language in regards to increasing joint outcomes for the groups. Across treatments, we find subjects that use gain frames and make reference to visuals aids during bargaining experience larger gains for the group, while loss frames and pro-self language experience larger gains for the individual through side payments. This finding suggests a bargainer's dilemma whether to employ language that claims a larger share of group's assets or employ language to increase joint gains.BACKGROUND The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran. METHODS From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes. RESULTS Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD. CONCLUSIONS The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.Various brain injuries lead to the activation of adult neural stem/progenitor cells in the mammalian hippocampus. Subsequent injury-induced neurogenesis appears to be essential for at least some aspects of the innate recovery in cognitive function observed following traumatic brain injury (TBI). It has previously been established that Apolipoprotein E (ApoE) plays a regulatory role in adult hippocampal neurogenesis, which is of particular interest as the presence of the human ApoE isoform ApoE4 leads to significant risk for the development of late-onset Alzheimer's disease, where impaired neurogenesis has been linked with disease progression. Moreover, genetically modified mice lacking ApoE or expressing the ApoE4 human isoform have been shown to impair adult hippocampal neurogenesis under normal conditions. Here, we investigate how controlled cortical impact (CCI) injury affects dentate gyrus development using hippocampal stereotactic injections of GFP-expressing retroviruses in wild-type (WT), ApoE-deficient and humanized (ApoE3 and ApoE4) mice. Infected adult-born hippocampal neurons were morphologically analyzed once fully mature, revealing significant attenuation of dendritic complexity and spine density in mice lacking ApoE or expressing the human ApoE4 allele, which may help inform how ApoE influences neurological diseases where neurogenesis is defective.It is standard practice to model site-to-site variability of substitution rates by discretizing a continuous distribution into a small number, K, of equiprobable rate categories. We demonstrate that the variance of this discretized distribution has an upper bound determined solely by the choice of K and the mean of the distribution. This bound can introduce biases into statistical inference, especially when estimating parameters governing site-to-site variability of substitution rates. Applications to two large collections of sequence alignments demonstrate that this upper bound is often reached in analyses of real data. When parameter estimation is of primary interest, additional rate categories or more flexible modeling methods should be considered.
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