A use-side trade margins matrix for the Andalusian economy

According to the National Accounting Systems proposed by United Nations (1993) and Eurostat (1996), use and make (or supply) matrices should be measured before goods and services are conveyed to the markets (basic values). Actually, the make table is defined in basic values (excluding trade and transport margins and net commodity taxes) whereas the use table is in purchasers' values (including them). This paper shows how these margins and taxes can be removed from the use table with the purpose of entering both of them in the so-called material balance equation. With respect to trade margins, our approach is based on the use-side procedure from the ESA-95 Input-Output Manual (Eurostat, 2002) and is also being applied to the forthcoming 2000 Andalusian Input-Output Framework.Input-output analysis, use and make matrices, trade margins, National Accounts

Evaluation of PCR and indirect enzyme-linked immunosorbent assay on milk samples for diagnosis of brucellosis in dairy cattle

A study was performed to evaluate the previously described PCR (C. Romero, C. Gamazo, M. Pardo, and I. López-Goñi, J. Clin. Microbiol. 33:615-617, 1995) for the diagnosis of brucellosis in dairy cattle. Milk samples from 56 Brucella milk culture-positive cattle and from 37 cattle from Brucella-free herds were examined for Brucella DNA by PCR and for specific antibodies by an indirect enzyme-linked immunosorbent assay (ELISA). The specificities of both tests were 100% when testing the milk samples from Brucella-free cattle. The milk samples from 49 infected cattle were positive by PCR (87.5% sensitivity), and 55 were positive by ELISA (98.2% sensitivity). A PCR-positive sample was negative by ELISA, and 7 ELISA-positive samples were PCR negative, yielding an observed proportion of agreement of 0.91 for the two tests. Although the results suggest that ELISA is a better screening test than PCR, the combined sensitivity of the two assays was 100%, and their simultaneous application could be more useful than one test alone for a rapid screening of brucellosis in dairy cattle

Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice

Vaccination appears to be the only rational prophylactic approach to control shigellosis. Unfortunately, there is still no safe and efficacious vaccine available. We investigated the protection conferred by a new vaccine containing outer membrane vesicles (OMVs) from Shigella flexneri with an adjuvant based on nanoparticles in an experimental model of shigellosis in mice. OMVs were encapsulated in poly(anhydride) nanoparticles prepared by a solvent displacement method with the copolymer PMV/MA. OMVs loaded into NPs (NP-OMVs) were homogeneous and spherical in shape, with a size of 197 nm (PdI = 0.06). BALB/c mice (females, 9-week-old, 20 ± 1 g) were immunized by intradermal, nasal, ocular (20 μg) or oral route (100 μg) with free or encapsulated OMV. Thirty-five days after administration, mice were infected intranasally with a lethal dose of S. flexneri (1 × 107 CFU). The new vaccine was able to protect fully against infection when it was administered via mucosa. By intradermal route the NP-OMVs formulation increased the protection from 20%, obtained with free extract, to 100%. Interestingly, both OMVs and OMV-NP induced full protection when administered by the nasal and conjuntival route. A strong association between the ratio of IL-12p40/IL-10 and protection was found. Moreover, low levels of IFN-γ correlate with protection. Under the experimental conditions used, the adjuvant did not induce any adverse effects. These results place OMVs among promising candidates to be used for vaccination against Shigellosis

At a glance:the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patients referred from 47 countries and diagnosed with NPC1 in our laboratory were analyzed. Patients’ clinical data were dissected using Human Phenotype Ontology (HPO) terms, and genotype–phenotype analysis was performed. The median age at diagnosis was 10.6 years (range 0–64.5 years), with 287 unique pathogenic/likely pathogenic (P/LP) variants identified, expanding NPC1 allelic heterogeneity. Importantly, 73 P/LP variants were previously unpublished. The most frequent variants detected were: c.3019C &gt; G, p.(P1007A), c.3104C &gt; T, p.(A1035V), and c.2861C &gt; T, p.(S954L). Loss of function (LoF) variants were significantly associated with earlier age at diagnosis, highly increased biomarker levels, and a visceral phenotype (abnormal abdomen and liver morphology). On the other hand, the variants p.(P1007A) and p.(S954L) were significantly associated with later age at diagnosis (p &lt; 0.001) and mildly elevated biomarker levels (p ≤ 0.002), consistent with the juvenile/adult form of NPC1. In addition, p.(I1061T), p.(S954L), and p.(A1035V) were associated with abnormality of eye movements (vertical supranuclear gaze palsy, p ≤ 0.05). We describe the largest and most heterogenous cohort of NPC1 patients published to date. Our results suggest that besides its utility in variant classification, the biomarker PPCS might serve to indicate disease severity/progression. In addition, we establish new genotype–phenotype relationships for “frequent” NPC1 variants.</p

Population stratification may bias analysis of PGC-1α as a modifier of age at Huntington disease motor onset

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation

Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington’s disease motor onset

Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3′ UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Valorisation of Biowastes for the Production of Green Materials Using Chemical Methods

With crude oil reserves dwindling, the hunt for a sustainable alternative feedstock for fuels and materials for our society continues to expand. The biorefinery concept has enjoyed both a surge in popularity and also vocal opposition to the idea of diverting food-grade land and crops for this purpose. The idea of using the inevitable wastes arising from biomass processing, particularly farming and food production, is, therefore, gaining more attention as the feedstock for the biorefinery. For the three main components of biomass—carbohydrates, lipids, and proteins—there are long-established processes for using some of these by-products. However, the recent advances in chemical technologies are expanding both the feedstocks available for processing and the products that be obtained. Herein, this review presents some of the more recent developments in processing these molecules for green materials, as well as case studies that bring these technologies and materials together into final products for applied usage